Biochemistry, Genetics and Molecular Biology › Molecular Biology

Porphyrin Metabolism and Disorders

Works Count: 38226

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Description

This cluster of papers explores the molecular mechanisms of heme biosynthesis, including the catalysis by cobalamin-dependent enzymes, genetic mutations leading to porphyrias, microbial production of vitamin B12, and the use of RNA interference therapy and liver transplantation for the treatment of related disorders. It also delves into metabolic engineering and genomic analysis related to heme biosynthesis pathways.

Keywords

Heme Biosynthesis; Vitamin B12; Porphyrias; Enzyme Catalysis; Genetic Mutations; Metabolic Engineering; RNA Interference Therapy; Liver Transplantation; Genomic Analysis; Biochemical Pathways

The inactivation of Fe-S cluster containing hydro-lyases by superoxide.

1993-10-01

Dennis H. Flint , Joseph F. Tuminello , M H Emptage

We report in this paper that highly purified Escherichia coli dihydroxy-acid dehydratase, fumarase A, fumarase B, and mammalian aconitase are inactivated by O2- with second order rate constants in the … We report in this paper that highly purified Escherichia coli dihydroxy-acid dehydratase, fumarase A, fumarase B, and mammalian aconitase are inactivated by O2- with second order rate constants in the range of 10(6) to 10(7) M-1 s-1. Each of these enzymes belongs to the hydro-lyase class and contains catalytically active [4Fe-4S] clusters. Simultaneous with inactivation by O2- is the release of iron from their clusters. Our working hypothesis is O2- inactivates these enzymes by oxidizing their clusters to an unstable oxidation state, and cluster degradation follows. Consistent with this hypothesis is our observation that spinach dihydroxy-acid dehydratase, a member of the hydro-lyase class that has a catalytically active [2Fe-2S] cluster, is not inactivated and does not lose iron in the presence of O2-. Porcine fumarase, a member of the hydro-lyase class that does not contain an Fe-S cluster, is also not inactivated by O2-. We also report the rate constants for the inactivation of E. coli dihydroxy-acid dehydratase, fumarase A, fumarase B, and mammalian aconitase by O2 are close to 2 x 10(2) M-1 s-1, and the rate constants for the inactivation of E. coli dihydroxy-acid dehydratase and mammalian aconitase by H2O2 are about 10(3) M-1 s-1. E. coli dihydroxy-acid dehydratase has been reported previously to be inactivated in vivo when cells are grown in hyperbaric O2, presumably due to the increased O2- generated under these conditions. We report here that E. coli fumarase A, fumarase B, and aconitase are also inactivated in vivo by hyperbaric O2. Thermodynamic parameters for the oxidation of the cluster of aconitase by O2- and O2 are calculated.

The Induction in Vitro of the Synthesis of δ-Aminolevulinic Acid Synthetase in Chemical Porphyria: A Response to Certain Drugs, Sex Hormones, and Foreign Chemicals

1966-03-01

S. Granick

1. A method is described for the primary growth of chick embryo liver cells on cover slips in culture, and the factors of the culture medium are considered that affect … 1. A method is described for the primary growth of chick embryo liver cells on cover slips in culture, and the factors of the culture medium are considered that affect the induction of porphyrin formation with certain chemicals. 2. A method is described for following δ-aminolevulinic acid synthetase (ALA synthetase) activity by the determination of porphyrin fluorescence developed in the cells on cover slips after induction with chemicals or drugs. 3. A nonchromatographic method is described for the determination of δ-aminolevulinic acid and aminoacetone in the range of 10-8 mole. 4. With allylisopropylacetamide as inducing chemical, an 8-fold increase in the mitochondrial ALA synthetase of chick embryo liver has been found. No other tissue tested was inducible. 5. After induction, porphyrin increased at almost a logarithmic rate for the first 12 hours. 6. The inducing action of the chemical is reversible. 7. The half-life of ALA synthetase in chick embryo liver cells in culture is 4 to 6 hours. 8. The chemicals and drugs which induce a porphyria in the chick embryo liver cells in culture may be separated into four classes: the barbiturates which contain three chemical groups that can individually induce; the collidines which contain two chemical groups; the sex steroids; and a miscellaneous class. 9. Evidence is presented that the control of ALA synthetase in the liver is by feedback repression in which heme may be the corepressor. No feedback inhibition was found. 10. The site for induction is proposed to be a site on a repressor which is competed for by heme and an inducing chemical. 11. Hepatic porphyria is postulated to be caused by a mutation in an operator gene that is poorly responsive to the repressor. The delay in appearance of symptoms of this disease until puberty suggests that sex steroids are the inducing chemicals.

Chemistry and biochemistry of B12

1999-01-01

Ruma Banerjee

CHEMISTRY OF B-12. B-12 History (H. Hogenkamp). X-ray Crystallography of B-12 (B. Krautler & C. Kratky). X-Ray Absorption Spectorscopy of B-12: Structural Changes of Intermediate States (M. Chance). Electronic Structure … CHEMISTRY OF B-12. B-12 History (H. Hogenkamp). X-ray Crystallography of B-12 (B. Krautler & C. Kratky). X-Ray Absorption Spectorscopy of B-12: Structural Changes of Intermediate States (M. Chance). Electronic Structure and Spectra of B-12: From Trans Effects to Protein Conformation I (J. Pratt). Electronic Structure and Spectra of B-12: From Trans Effects to Protein Conformation II (J. Pratt). EPR Spectroscopy of B-12-Dependent Enzymes (G. Gerfen). NMR Spectroscopy of B-12 (K. Brown). Vibrational Spectroscopy of B-12 and Related Compounds (L. Marzilli & S. Hirota). Magnetic Field Dependence of Cobalamin Photochemistry and Enzymes (C. Grissom). Stereospecificity of the Coenzyme B-12 Catalyzed Rearrangements and the Role of Negative Catalysis (J. Retey). Modeling the Structure of Cobalt Corrins by Molecular Mechanics and Molecular Dynamics Methods (H. Marques). B-12 Electrochemistry and Organometallic Electrochemical Synthesis (B. Krautler). BIOCHEMISTRY AND BIOLOGY OF B-12. B-12 and Nutrition (S. Stabler). Inborn Errors of Cobalamin Metabolism (D. Rosenblatt & W. Fenton). Diagnostic and Therapeutic Analogs of Cobalamin (H. Hogenkamp, et al.). Intrinsic Factor and Haptocorrin and Their Receptors (D. Alpers & G. Russell-Jones). Transcobalamin II (S. Rothenberg, et al.). Mammalian Receptors of Vitamin B-12-Binding Proteins (S. Moestrup & P. Verroust). Cobalamin Transport in Bacteria (C. Bradbeer). Biosynthesis of B-12 in the Aerobic Organism Pseudomonas denitrificans (A. Battersby & F. Leeper). B-12 Biosynthesis: The Anaerobic Pathway (A. Scott, et al.). Biosynthesis of the 5-6 Dimethylbenzimidazole Moiety of Cobalamin and of the Other Bases Found in Natural Corrinoids (P. Renz). Regulation of Adenosylcobalamin Biosynthesis in Salmonella typhimurium (J. Semerena). X-ray Crystallography of B-12 Enzymes: Methylmalonyl-CoA Mutase and Methionine Synthase (M. Ludwig & P. Evans). The Acetogenic Corriniod Proteins (S. Ragsdale). The Role of Corrinoids in Methanogenesis (K. Sauer & R. Thauer). Methionine Synthase (R. Matthews). Methylmalonyl-CoA Mutase (R. Banerjee & S. Chowdhury). Ribonucleotide Reductases (M. Fontecave & E. Mulliez). Glutamate Mutase and 2-Methyleneglutarate Mutase (W. Buckel, et al.). Diol Dehydrase and Glycerol Dehydrase (T. Toraya). Ethanolamine Ammonia-Lyase (V. Bandarian & G. Reed). Anomutases (P. Frey). Isobutyryl-CoA Mutase (K. Zerbe-Burkhardt, et al.). Reductive Dehalogenases (G. Wohlfarth & G. Diekert).

The ultraviolet fluorescence of proteins in neutral solution

1960-08-01

F. W. J. Teale

Research Article| August 01 1960 The ultraviolet fluorescence of proteins in neutral solution F. W. J. Teale F. W. J. Teale 1Department of Biochemistry, The University, Sheffield 10 Search for … Research Article| August 01 1960 The ultraviolet fluorescence of proteins in neutral solution F. W. J. Teale F. W. J. Teale 1Department of Biochemistry, The University, Sheffield 10 Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1960) 76 (2): 381–388. https://doi.org/10.1042/bj0760381 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation F. W. J. Teale; The ultraviolet fluorescence of proteins in neutral solution. Biochem J 1 August 1960; 76 (2): 381–388. doi: https://doi.org/10.1042/bj0760381 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1960 CAMBRIDGE UNIVERSITY PRESS1960 Article PDF first page preview Close Modal You do not currently have access to this content.

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Determination of [3H]- and [14C]hematoporphyrin derivative distribution in malignant and normal tissue.

1979-01-01

Charles J. Gomer , Thomas J. Dougherty

The synthesis and tissue-localizing ability of [14C]- and [3H]hematoporphyrin derivative (HPD) in mice have been described. Tissue levels and distributions were the same for both radioactive compounds, indicating that in … The synthesis and tissue-localizing ability of [14C]- and [3H]hematoporphyrin derivative (HPD) in mice have been described. Tissue levels and distributions were the same for both radioactive compounds, indicating that in vivo tritium exchange did not occur with [3H]HPD. The amount of [14C]HPD or [3H]HPD which localized in the transplanted tumor tissue of mice at various times following i.p. injection (10 mg/kg) was higher than in skin or muscle tissue but was less than in liver, kidney, or spleen tissue. These results tend to disprove the generalization that HPD accumulates in malignant tissue to a higher degree than in all normal tissue. It is also reported that gross visualization of porphyrin fluorescence cannot be correlated with actual tissue concentrations of the dye.

Genetic aspects of bacterial endospore formation

1976-12-01

P. J. Piggot , J. G. Coote

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Heme regulates transcription of the CYC1 gene of S. cerevisiae via an upstream activation site

1983-04-01

Leonard Guarente , Thomas L. Mason

Mechanisms of Coenzyme B 12 -Dependent Rearrangements

1985-02-22

Jack Halpern

Coenzyme B 12 serves as a cofactor in various enzymatic reactions in which a hydrogen atom is interchanged with a substituent on an adjacent carbon atom. Measurement of the dissociation … Coenzyme B 12 serves as a cofactor in various enzymatic reactions in which a hydrogen atom is interchanged with a substituent on an adjacent carbon atom. Measurement of the dissociation energy of the coenzyme's cobalt-carbon bond and studies of the rearrangement of model free radicals related to those derived from methylmalonyl-coenzyme A suggest that these enzymatic reactions occur through homolytic dissociation of the coenzyme's cobalt-carbon bond, abstraction of a hydrogen atom from the substrate by the coenzyme-derived 5′-deoxyadenosyl radical, and rearrangement of the resulting substrate radical. The only role thus far identified for coenzyme B 12 in these reactions—namely, that of a free radical precursor—reflects the weakness, and facile dissociation, of the cobalt-carbon bond.

Antioxidant functions of carotenoids

1989-01-01

Norman I. Krinsky

Crystalline Vitamin B 12

1948-04-16

Edward L. Rickes , Norman G. Brink , Frank R. Koniuszy +2 more

Algae acquire vitamin B12 through a symbiotic relationship with bacteria

2005-11-01

Martin T. Croft , Andrew D. Lawrence , Evelyne Raux‐Deery +2 more

A Ni-Fe-Cu Center in a Bifunctional Carbon Monoxide Dehydrogenase/ Acetyl-CoA Synthase

2002-10-18

Tzanko Doukov , T.M. Iverson , Javier Seravalli +2 more

A metallocofactor containing iron, sulfur, copper, and nickel has been discovered in the enzyme carbon monoxide dehydrogenase/acetyl-CoA (coenzyme A) synthase from Moorella thermoacetica (f. Clostridium thermoaceticum ). Our structure at … A metallocofactor containing iron, sulfur, copper, and nickel has been discovered in the enzyme carbon monoxide dehydrogenase/acetyl-CoA (coenzyme A) synthase from Moorella thermoacetica (f. Clostridium thermoaceticum ). Our structure at 2.2 angstrom resolution reveals that the cofactor responsible for the assembly of acetyl-CoA contains a [Fe 4 S 4 ] cubane bridged to a copper-nickel binuclear site. The presence of these three metals together in one cluster was unanticipated and suggests a newly discovered role for copper in biology. The different active sites of this bifunctional enzyme complex are connected via a channel, 138 angstroms long, that provides a conduit for carbon monoxide generated at the C-cluster on one subunit to be incorporated into acetyl-CoA at the A-cluster on the other subunit.

Preventing lead poisoning in young children

1978-10-01

Herbert L. Needleman , Vernon N. Houk , Irwin H. Billick +7 more

Porphyrin localization and treatment of tumors

1985-09-01

E. J. Land

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Crystal Structure of Methyl-Coenzyme M Reductase: The Key Enzyme of Biological Methane Formation

1997-11-21

Ulrich Ermler , Wolfgang Grabarse , Seigo Shima +2 more

Methyl–coenzyme M reductase (MCR), the enzyme responsible for the microbial formation of methane, is a 300-kilodalton protein organized as a hexamer in an α 2 β 2 γ 2 arrangement. … Methyl–coenzyme M reductase (MCR), the enzyme responsible for the microbial formation of methane, is a 300-kilodalton protein organized as a hexamer in an α 2 β 2 γ 2 arrangement. The crystal structure of the enzyme from Methanobacterium thermoautotrophicum , determined at 1.45 angstrom resolution for the inactive enzyme state MCR ox1-silent , reveals that two molecules of the nickel porphinoid coenzyme F 430 are embedded between the subunits α, α′, β, and γ and α′, α, β′, and γ′, forming two identical active sites. Each site is accessible for the substrate methyl–coenzyme M through a narrow channel locked after binding of the second substrate coenzyme B. Together with a second structurally characterized enzyme state (MCR silent ) containing the heterodisulfide of coenzymes M and B, a reaction mechanism is proposed that uses a radical intermediate and a nickel organic compound.

The 2‐His‐1‐Carboxylate Facial Triad — An Emerging Structural Motif in Mononuclear Non‐Heme Iron(II) Enzymes

1997-12-01

Eric L. Hegg , Lawrence Que

A 2‐His‐1‐carboxylate facial triad is a common feature of the active sites in a number of mononuclear non‐heme iron(II) enzymes. This structural motif was established crystallographically for five different classes … A 2‐His‐1‐carboxylate facial triad is a common feature of the active sites in a number of mononuclear non‐heme iron(II) enzymes. This structural motif was established crystallographically for five different classes of enzymes and inferred from sequence similarity for two other classes. The 2‐His‐1‐carboxylate facial triad anchors the iron in the active site and at the same time maintains three additional cis ‐oriented sites. These sites can be used to bind other endogenous ligands or exogenous ligands such as substrate and/or O 2 , giving the metal center great flexibility to use different mechanistic strategies to perform a variety of chemical transformations.

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Biochemistry of methanogenesis: a tribute to Marjory Stephenson:1998 Marjory Stephenson Prize Lecture

1998-09-01

Rudolf K. Thauer

Max-Planck-Institut für terrestrische Mikrobiologie, Karl-von-Frisch-Straße, D-35043 Marburg, and Laboratorium für Mikrobiologie, Fachbereich Biologie, Philipps-Universität, Karl-von-Frisch-Straße, D-35032 Marburg, Germany In 1933, Stephenson & Stickland (1933a) published that they had isolated from … Max-Planck-Institut für terrestrische Mikrobiologie, Karl-von-Frisch-Straße, D-35043 Marburg, and Laboratorium für Mikrobiologie, Fachbereich Biologie, Philipps-Universität, Karl-von-Frisch-Straße, D-35032 Marburg, Germany In 1933, Stephenson & Stickland (1933a) published that they had isolated from river mud, by the single cell technique, a methanogenic organism capable of growth in an inorganic medium with formate as the sole carbon source.

The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase.

1968-10-01

R Tenhunen , Harvey S. Marver , R. Schmid

In the intact organism heme and hemoglobin are converted nearly quantitatively to bilirubin. 1 2 Although several model systems have been proposed, the exact mechanism and the individual steps of … In the intact organism heme and hemoglobin are converted nearly quantitatively to bilirubin. 1 2 Although several model systems have been proposed, the exact mechanism and the individual steps of this conversion remain unknown.Lemberg3 suggested a coupled oxidation with ascorbate and molecular oxygen, which in vitro leads to formation of the bile pigment precursors choleglobin and verdohemochrome; on acidification, biliverdin is obtained.This nonenzymatic system is unlikely to reflect the physiologic mechanism of heme degradation because it results in formation of a mixture of biliverdin isomers,4 whereas in

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A comparison of concentrations of lead in human tissues.

1975-05-01

P.S.I. Barry

This postmortem study of lead concentrations in the tissues of 129 subjects is an extension to a report by Barry and Mossman (1970). Lead concentrations in bone greatly exceeded the … This postmortem study of lead concentrations in the tissues of 129 subjects is an extension to a report by Barry and Mossman (1970). Lead concentrations in bone greatly exceeded the concentrations in soft tissues and were highest in the dense bones. Bone lead concentrations increased with age in both sexes, more especially in male subjects and in dense bone, varying between mean values of 2-16 ppm in the ribs of children to over 50 ppm in the dense petrous temporal bones of elderly male adults. Male adults contained over 30% more lead in their bones than females. Mean concentrations of lead in the soft tissues varied from less than 0-1 ppm in organs such as muscle and heart to over 2 ppm in the aorta. In most tissues with lead values in excess of 0-2 ppm the male concentrations exceeded female values by about 30%. With the exception of the aorta, spleen, lung, and prostate, lead concentrations did not increase with age in the soft tissues of either sex after about the second decade of life. Children showed concentrations of lead in their soft tissues comparable to female adults, but the concentrations in bone were much lower. It is suggested that children do not possess the same capacity as adults to retain lead in bone. In male adults occupationally exposed to lead the concentrations of lead in bone exceeded the concentrations in unexposed male adults within the same age group by two-to three-fold. Soft tissue lead concentrations between the two groups were less divergent. An assessment of the total body burden of lead revealed higher levels in adult male subjects than in females at mean values of 164-8 mg compared to 103-6 mg, respectively. Over 90% of the total body burden of lead in adults was in bone, of which over 70% was in dense bone. Male adults occupationally exposed to lead had mean total body burdens of 566-4 mg Pb, of which 97% was in bone. The release of lead from bone in conjunction with calcium was not considered to be of physiological significance. Lead concentrations of hair and nails were higher than soft tissue lead concentrations and varied widely. Hair lead measurements were not considered to provide a reliable assessment of lead absorption. The concentrations of lead in tissues of a mixed group of subjects with no known occupational exposure to lead have been shown to be comparable to the findings in earlier studies. Present levels of lead in the environment are not considered to be a hazard to the health of the population in general.

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Recommendations for the Diagnosis and Treatment of the Acute Porphyrias

2005-03-15

Karl E. Anderson , Joseph R. Bloomer , Herbert L. Bonkovsky +4 more

The acute porphyrias, 4 inherited disorders of heme biosynthesis, cause life-threatening attacks of neurovisceral symptoms that mimic many other acute medical and psychiatric conditions. Lack of clinical recognition often delays … The acute porphyrias, 4 inherited disorders of heme biosynthesis, cause life-threatening attacks of neurovisceral symptoms that mimic many other acute medical and psychiatric conditions. Lack of clinical recognition often delays effective treatment, and inappropriate diagnostic tests may lead to misdiagnosis and inappropriate treatment. We review the clinical manifestations, pathophysiology, and genetics of the acute porphyrias and provide recommendations for diagnosis and treatment on the basis of reviews of the literature and clinical experience. An acute porphyria should be considered in many patients with unexplained abdominal pain or other characteristic symptoms. The diagnosis can be rapidly confirmed by demonstration of a markedly increased urinary porphobilinogen level by using a single-void urine specimen. This specimen should also be saved for quantitative measurement of porphobilinogen, 5-aminolevulinic acid, and total porphyrin levels. Intravenous hemin therapy, started as soon as possible, is the most effective treatment. Intravenous glucose alone is appropriate only for mild attacks (mild pain, no paresis or hyponatremia) or until hemin is available. Precipitating factors should be eliminated, and appropriate supportive and symptomatic therapy should be initiated. Prompt diagnosis and treatment greatly improve prognosis and may prevent development of severe or chronic neuropathic symptoms. We recommend identification of at-risk relatives through enzymatic or gene studies.

The Thyroid Gland.

1965-12-01

Sidney H. Ingbar

The rapid growth of knowledge in recent years concerning the physiology and biochemistry of the thyroid hormones and the pathogenesis and treatment of thyroid diseases has no doubt been responsible … The rapid growth of knowledge in recent years concerning the physiology and biochemistry of the thyroid hormones and the pathogenesis and treatment of thyroid diseases has no doubt been responsible for the recent spate of books dealing with these subjects. Among the most comprehensive and stimulating of these isThe Thyroid Gland. This two volume presentation is comprised of 28 chapters by an international aggregation of 36 contributors, each an acknowledged authority in the field with which he deals. The books are edited by Rosalind Pitt-Rivers and W. R. Trotter, who are themselves distinguished authorities in basic and clinical thyroidology. This expertise and scholarship is reflected in the comprehensive manner in which the subjects are usually discussed and in the extensive bibliographies which accompany them. Volume 1 is concerned principally with the structure and function of the thyroid gland, the peripheral metabolism, and the metabolic effects of thyroid hormones.

FLU: A negative regulator of chlorophyll biosynthesis in Arabidopsis thaliana

2001-10-16

Rasa Meskauskiene , Mena Nater , David Goslings +3 more

Tetrapyrroles such as chlorophylls and bacteriochlorophylls play a fundamental role in the energy absorption and transduction activities of photosynthetic organisms. Because of these molecules, however, photosynthetic organisms are also prone … Tetrapyrroles such as chlorophylls and bacteriochlorophylls play a fundamental role in the energy absorption and transduction activities of photosynthetic organisms. Because of these molecules, however, photosynthetic organisms are also prone to photooxidative damage. They had to evolve highly efficient strategies to control tetrapyrrole biosynthesis and to prevent the accumulation of free intermediates that potentially are extremely destructive when illuminated. In higher plants, the metabolic flow of tetrapyrrole biosynthesis is regulated at the step of δ-aminolevulinic acid synthesis. This regulation previously has been attributed to feedback control of Glu tRNA reductase, the first enzyme committed to tetrapyrrole biosynthesis, by heme. With the recent discovery of chlorophyll intermediates acting as signals that control both nuclear gene activities and tetrapyrrole biosynthesis, it seems likely that heme is not the only regulator of this pathway. A genetic approach was used to identify additional factors involved in the control of tetrapyrrole biosynthesis. In Arabidopsis thaliana , we have found a negative regulator of tetrapyrrole biosynthesis, FLU, which operates independently of heme and seems to selectively affect only the Mg 2+ branch of tetrapyrrole biosynthesis. The identity of this protein was established by map-based cloning and sequencing the FLU gene. FLU is a nuclear-encoded plastid protein that, after import and processing, becomes tightly associated with plastid membranes. It is unrelated to any of the enzymes known to be involved in tetrapyrrole biosynthesis. Its predicted features suggest that FLU mediates its regulatory effect through interaction with enzymes involved in chlorophyll synthesis.

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Chemistry and Enzymology of Vitamin B12

2005-04-02

Kenneth L. Brown

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemistry and Enzymology of Vitamin B12Kenneth L. BrownView Author Information Department of Chemistry and Biochemistry, Ohio University, Athens, Ohio 45701 Cite this: Chem. Rev. 2005, 105, 6, … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemistry and Enzymology of Vitamin B12Kenneth L. BrownView Author Information Department of Chemistry and Biochemistry, Ohio University, Athens, Ohio 45701 Cite this: Chem. Rev. 2005, 105, 6, 2075–2150Publication Date (Web):April 2, 2005Publication History Received25 August 2004Published online2 April 2005Published inissue 1 June 2005https://pubs.acs.org/doi/10.1021/cr030720zhttps://doi.org/10.1021/cr030720zresearch-articleACS PublicationsCopyright © 2005 American Chemical SocietyRequest reuse permissionsArticle Views7176Altmetric-Citations464LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Alkyls,Kinetic parameters,Ligands,Monomers,Peptides and proteins Get e-Alerts

Complete proton and carbon-13 assignments of coenzyme B12 through the use of new two-dimensional NMR experiments

1986-07-01

Michael F. Summers , Luigi G. Marzilli , Ad Bax

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTComplete proton and carbon-13 assignments of coenzyme B12 through the use of new two-dimensional NMR experimentsMichael F. Summers, Luigi G. Marzilli, and Ad. BaxCite this: J. Am. … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTComplete proton and carbon-13 assignments of coenzyme B12 through the use of new two-dimensional NMR experimentsMichael F. Summers, Luigi G. Marzilli, and Ad. BaxCite this: J. Am. Chem. Soc. 1986, 108, 15, 4285–4294Publication Date (Print):July 1, 1986Publication History Published online1 May 2002Published inissue 1 July 1986https://pubs.acs.org/doi/10.1021/ja00275a008https://doi.org/10.1021/ja00275a008research-articleACS PublicationsRequest reuse permissionsArticle Views794Altmetric-Citations642LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

The trans-influence: its measurement and significance

1973-05-01

Trevor G. Appleton , H. C. Clark , Leo E. Manzer

Spin-state/stereochemical relationships in iron porphyrins: implications for the hemoproteins

1981-12-01

W. Robert Scheidt , Christopher A. Reed

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSpin-state/stereochemical relationships in iron porphyrins: implications for the hemoproteinsW. Robert Scheidt and Christopher A. ReedCite this: Chem. Rev. 1981, 81, 6, 543–555Publication Date (Print):December 1, 1981Publication History … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSpin-state/stereochemical relationships in iron porphyrins: implications for the hemoproteinsW. Robert Scheidt and Christopher A. ReedCite this: Chem. Rev. 1981, 81, 6, 543–555Publication Date (Print):December 1, 1981Publication History Published online1 May 2002Published inissue 1 December 1981https://pubs.acs.org/doi/10.1021/cr00046a002https://doi.org/10.1021/cr00046a002research-articleACS PublicationsRequest reuse permissionsArticle Views3005Altmetric-Citations536LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Picket fence porphyrins. Synthetic models for oxygen binding hemoproteins

1975-03-01

James P. Collman , Robert R. Gagnè , Christopher A. Reed +3 more

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPicket fence porphyrins. Synthetic models for oxygen binding hemoproteinsJames P. Collman, Robert R. Gagne, Christopher Reed, Thomas R. Halbert, George Lang, and Ward T. RobinsonCite this: J. … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPicket fence porphyrins. Synthetic models for oxygen binding hemoproteinsJames P. Collman, Robert R. Gagne, Christopher Reed, Thomas R. Halbert, George Lang, and Ward T. RobinsonCite this: J. Am. Chem. Soc. 1975, 97, 6, 1427–1439Publication Date (Print):March 1, 1975Publication History Published online1 May 2002Published inissue 1 March 1975https://pubs.acs.org/doi/10.1021/ja00839a026https://doi.org/10.1021/ja00839a026research-articleACS PublicationsRequest reuse permissionsArticle Views6317Altmetric-Citations683LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

CHROMATOGRAPHlC SEPARATION OF HUMAN BRAIN GANGLIOSIDES*

1963-09-01

Lars Svennerholm

The Metabolic Basis of Inherited Diseases

1972-08-01

R.K. Winkelmann

Some books belong in every medical library. Volumes such as Christopher'sSurgery; Allen, Barker, and Hines'Peripheral Vascular Disease; and Goodman and Gilman'sPharmacologyare examples. The current book under review is another to … Some books belong in every medical library. Volumes such as Christopher'sSurgery; Allen, Barker, and Hines'Peripheral Vascular Disease; and Goodman and Gilman'sPharmacologyare examples. The current book under review is another to add. This edition has been completely rewritten by knowledgeable authors who write clearly and in concise detail about each subject. The historical description of cases is included. The pertinent clinical information is summarized, the metabolic and biochemical pathways are illustrated, genetic variations are discussed, and the literature summarized so that each chapter is a delight to read. The volume begins with an introduction to molecular genetics and proceeds to establish the utility of the approach to clinical medicine. The chapters on albinism by Fitzpatrick and Quevedo and on porphyria by Rudi Schmid are good. The Dorfman chapter on mucopolysaccharidoses, the Fredrickson chapters on lipoprotein and lipid disease, and the chapter on Refsum's syndrome are examples of

Attachment of a 40-base-pair G + C-rich sequence (GC-clamp) to genomic DNA fragments by the polymerase chain reaction results in improved detection of single-base changes.

1989-01-01

Val C. Sheffield , David R. Cox , Leonard S. Lerman +1 more

Denaturing gradient gel electrophoresis (DGGE) can be used to distinguish two DNA molecules that differ by as little as a single-base substitution. This method detects approximately 50% of all possible … Denaturing gradient gel electrophoresis (DGGE) can be used to distinguish two DNA molecules that differ by as little as a single-base substitution. This method detects approximately 50% of all possible single-base changes in DNA fragments ranging from 50 to approximately 1000 base pairs. To increase the number of single-base changes that can be distinguished by DGGE, we used the polymerase chain reaction to attach a 40-base-pair G + C-rich sequence, designated a GC-clamp, to one end of amplified DNA fragments that encompass regions of the mouse and human beta-globin genes. We show that this GC-clamp allows the detection of mutations, including the hemoglobin sickle (HbS) and hemoglobin C (HbC) mutations within the human beta-globin gene, that were previously indistinguishable by DGGE. In addition to providing an easy way to attach a GC-clamp to genomic DNA fragments, the polymerase chain reaction technique greatly increases the sensitivity of DGGE. With this approach, DNA fragments derived from less than 5 ng of human genomic DNA can be detected by ethidium bromide staining of the gel, obviating the need for radioactive probes. These improvements extend the applicability of DGGE for the detection of polymorphisms and mutations in genomic and cloned DNA.

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Biochemistry, Cellular and Molecular Biology, and Physiological Roles of the Iodothyronine Selenodeiodinases

2002-02-01

Antônio C. Bianco , Domenico Salvatore , Balázs Gereben +2 more

The goal of this review is to place the exciting advances that have occurred in our understanding of the molecular biology of the types 1, 2, and 3 (D1, D2, … The goal of this review is to place the exciting advances that have occurred in our understanding of the molecular biology of the types 1, 2, and 3 (D1, D2, and D3, respectively) iodothyronine deiodinases into a biochemical and physiological context. We review new data regarding the mechanism of selenoprotein synthesis, the molecular and cellular biological properties of the individual deiodinases, including gene structure, mRNA and protein characteristics, tissue distribution, subcellular localization and topology, enzymatic properties, structure-activity relationships, and regulation of synthesis, inactivation, and degradation. These provide the background for a discussion of their role in thyroid physiology in humans and other vertebrates, including evidence that D2 plays a significant role in human plasma T3 production. We discuss the pathological role of D3 overexpression causing "consumptive hypothyroidism" as well as our current understanding of the pathophysiology of iodothyronine deiodination during illness and amiodarone therapy. Finally, we review the new insights from analysis of mice with targeted disruption of the Dio2 gene and overexpression of D2 in the myocardium.

The Biochemistry of Desferrioxamine and its Relation to Iron Metabolism

1964-10-01

H. Keberle

Zinc coordination sphere in biochemical zinc sites.

2001-01-01

David S. Auld

Operator sequences of the aerobactin operon of plasmid ColV-K30 binding the ferric uptake regulation (fur) repressor

1987-06-01

Vı́ctor de Lorenzo , Sechan Wee , Marta Herrero +1 more

The promoter region of the pColV-K30-encoded operon specifying biosynthesis and transport of the siderophore aerobactin was subjected to deletion analysis to determine the smallest DNA sequence affording iron regulation of … The promoter region of the pColV-K30-encoded operon specifying biosynthesis and transport of the siderophore aerobactin was subjected to deletion analysis to determine the smallest DNA sequence affording iron regulation of a iucA'-'lacZ gene fusion. A 78-base-pair (bp) region containing the main (P1) promoter retained the character of inducibility under iron starvation. A 250-bp fragment carrying this sequence was examined for protection against DNase I by the Fur protein, the product of a gene (fur) required for negative control of several iron-regulated functions. The DNase I footprints, in the presence of various divalent heavy-metal ions added as corepressors, revealed two contiguous binding sites with different lengths and affinities for Fur. Increased concentrations of the protein appeared to elicit formation of repressor oligomers which bind to the upstream and downstream regions of the P1 promoter in a metal-dependent fashion, but with a presently undefined stoichiometry. The primary site for Fur binding spans 31 bp and contains two overlapping symmetry dyads which share the sequence 5'-TCATT-3'. It also contains extensive homology with a 19-bp consensus sequence for iron-regulated genes as deduced from comparison with the fhuA and fepA putative promoter sequences.

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Enzymes: Units of Biological Structure and Function

1956-10-13

Oliver H. Gaebler

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor … Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal

The Many Faces of Vitamin B12: Catalysis by Cobalamin-Dependent Enzymes

2003-03-25

Ruma Banerjee , Stephen W. Ragsdale

Vitamin B12 is a complex organometallic cofactor associated with three subfamilies of enzymes: the adenosylcobalamin-dependent isomerases, the methylcobalamin-dependent methyltransferases, and the dehalogenases. Different chemical aspects of the cofactor are exploited … Vitamin B12 is a complex organometallic cofactor associated with three subfamilies of enzymes: the adenosylcobalamin-dependent isomerases, the methylcobalamin-dependent methyltransferases, and the dehalogenases. Different chemical aspects of the cofactor are exploited during catalysis by the isomerases and the methyltransferases. Thus, the cobalt-carbon bond ruptures homolytically in the isomerases, whereas it is cleaved heterolytically in the methyltransferases. The reaction mechanism of the dehalogenases, the most recently discovered class of B12 enzymes, is poorly understood. Over the past decade our understanding of the reaction mechanisms of B12 enzymes has been greatly enhanced by the availability of large amounts of enzyme that have afforded detailed structure-function studies, and these recent advances are the subject of this review.

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Microbial production of vitamin B 12

2002-03-01

Martin J. Warren

COBALAMIN (COENZYME B12): Synthesis and Biological Significance

1996-10-01

JR Roth , JG Lawrence , TA Bobik

This review examines deoxyadenosylcobalamin (Ado-B 12 ) biosynthesis, transport, use, and uneven distribution among living forms. We describe how genetic analysis of enteric bacteria has contributed to these issues. Two … This review examines deoxyadenosylcobalamin (Ado-B 12 ) biosynthesis, transport, use, and uneven distribution among living forms. We describe how genetic analysis of enteric bacteria has contributed to these issues. Two pathways for corrin ring formation have been found–an aerobic pathway (in P. denitrificans) and an anaerobic pathway (in P. shermanii and S. typhimurium)–that differ in the point of cobalt insertion. Analysis of B 12 transport in E. coli reveals two systems: one (with two proteins) for the outer membrane, and one (with three proteins) for the inner membrane. To account for the uneven distribution of B 12 in living forms, we suggest that the B 12 synthetic pathway may have evolved to allow anaerobic fermentation of small molecules in the absence of an external electron acceptor. Later, evolution of the pathway produced siroheme, (allowing use of inorganic electron acceptors), chlorophyll (O 2 production), and heme (aerobic respiration). As oxygen became a larger part of the atmosphere, many organisms lost fermentative functions and retained dependence on newer, B 12 functions that did not involve fermentation. Paradoxically, Salmonella spp. synthesize B 12 only anaerobically but can use B 12 (for degradation of ethanolamine and propanediol) only with oxygen. Genetic analysis of the operons for these degradative functions indicate that anaerobic degradation is important. Recent results suggest that B 12 can be synthesized and used during anaerobic respiration using tetrathionate (but not nitrate or fumarate) as an electron acceptor. The branch of enteric taxa from which Salmonella spp. and E. coli evolved appears to have lost the ability to synthesize B 12 and the ability to use it in propanediol and glycerol degradation. Salmonella spp., but not E. coli, have acquired by horizontal transfer the ability to synthesize B 12 and degrade propanediol. The acquired ability to degrade propanediol provides the selective force that maintains B 12 synthesis in this group.

Energy conservation via electron bifurcating ferredoxin reduction and proton/Na+ translocating ferredoxin oxidation

2012-07-16

Wolfgang Buckel , Rudolf K. Thauer

Heme Enzyme Structure and Function

2014-01-08

T.L. Poulos

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTHeme Enzyme Structure and FunctionThomas L. Poulos*View Author Information Departments of Molecular Biology & Biochemistry, Pharmaceutical Sciences, and Chemistry, University of California, Irvine, Irvine, California 92697-3900*E-mail: [email … ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTHeme Enzyme Structure and FunctionThomas L. Poulos*View Author Information Departments of Molecular Biology & Biochemistry, Pharmaceutical Sciences, and Chemistry, University of California, Irvine, Irvine, California 92697-3900*E-mail: [email protected]. Phone: 949-824-7020.Cite this: Chem. Rev. 2014, 114, 7, 3919–3962Publication Date (Web):January 8, 2014Publication History Received30 July 2013Published online8 January 2014Published inissue 9 April 2014https://pubs.acs.org/doi/10.1021/cr400415khttps://doi.org/10.1021/cr400415kreview-articleACS PublicationsCopyright © 2014 American Chemical SocietyRequest reuse permissionsArticle Views21754Altmetric-Citations1023LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Bioinorganic chemistry,Charge transfer,Crystal structure,Peptides and proteins,Redox reactions Get e-Alerts

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ISOLATION AND CHARACTERIZATION OF RIBOSOMAL RIBONUCLEIC ACID

1965-07-01

K.S. Kirby

1. Ribosomal RNA has been prepared by extracting tissues with a phenol-cresol mixture, and ribosomal RNA can be selectively precipitated with m-cresol. No rapidly labelled RNA was associated with this … 1. Ribosomal RNA has been prepared by extracting tissues with a phenol-cresol mixture, and ribosomal RNA can be selectively precipitated with m-cresol. No rapidly labelled RNA was associated with this material. 2. However, if RNA and DNA are extracted with 4-aminosalicylate and phenol-cresol mixture and the nucleic acids precipitated, DNA, glycogen and s-RNA (transfer RNA) can be extracted with 3m-sodium acetate and in this case rapidly labelled RNA remains associated with the ribosomal RNA. 3. The ribosomal RNA is stable in the presence of concentrated salt solution and, although the secondary structure is lost by heating at 70 degrees in 10mm-sodium acetate, it can be re-formed in the presence of 200mm-sodium acetate. 4. The 28s and 18s components have been separated and their base compositions determined.

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�ber das Vitamin B12-Bed�rfnis phototropher Schwefelbakterien

1966-01-01

Norbert Pfennig , Klaus Dieter Lippert

Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria

2020-06-10

Manisha Balwani , Eliane Sardh , Paolo Ventura +7 more

Up-regulation of hepatic delta-aminolevulinic acid synthase 1 (ALAS1), with resultant accumulation of delta-aminolevulinic acid (ALA) and porphobilinogen, is central to the pathogenesis of acute attacks and chronic symptoms in acute … Up-regulation of hepatic delta-aminolevulinic acid synthase 1 (ALAS1), with resultant accumulation of delta-aminolevulinic acid (ALA) and porphobilinogen, is central to the pathogenesis of acute attacks and chronic symptoms in acute hepatic porphyria. Givosiran, an RNA interference therapy, inhibits ALAS1 expression.In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned symptomatic patients with acute hepatic porphyria to receive either subcutaneous givosiran (2.5 mg per kilogram of body weight) or placebo monthly for 6 months. The primary end point was the annualized rate of composite porphyria attacks among patients with acute intermittent porphyria, the most common subtype of acute hepatic porphyria. (Composite porphyria attacks resulted in hospitalization, an urgent health care visit, or intravenous administration of hemin at home.) Key secondary end points were levels of ALA and porphobilinogen and the annualized attack rate among patients with acute hepatic porphyria, along with hemin use and daily worst pain scores in patients with acute intermittent porphyria.A total of 94 patients underwent randomization (48 in the givosiran group and 46 in the placebo group). Among the 89 patients with acute intermittent porphyria, the mean annualized attack rate was 3.2 in the givosiran group and 12.5 in the placebo group, representing a 74% lower rate in the givosiran group (P<0.001); the results were similar among the 94 patients with acute hepatic porphyria. Among the patients with acute intermittent porphyria, givosiran led to lower levels of urinary ALA and porphobilinogen, fewer days of hemin use, and better daily scores for pain than placebo. Key adverse events that were observed more frequently in the givosiran group were elevations in serum aminotransferase levels, changes in serum creatinine levels and the estimated glomerular filtration rate, and injection-site reactions.Among patients with acute intermittent porphyria, those who received givosiran had a significantly lower rate of porphyria attacks and better results for multiple other disease manifestations than those who received placebo. The increased efficacy was accompanied by a higher frequency of hepatic and renal adverse events. (Funded by Alnylam Pharmaceuticals; ENVISION ClinicalTrials.gov number, NCT03338816.).

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How a Protein Binds B 12 : A 3.0 Å X-Ray Structure of B 12 -Binding Domains of Methionine Synthase

1994-12-09

Catherine L. Drennan , Sha Huang , James T. Drummond +2 more

The crystal structure of a 27-kilodalton methylcobalamin-containing fragment of methionine synthase from Escherichia coli was determined at 3.0 Å resolution. This structure depicts cobalamin-protein interactions and reveals that the corrin … The crystal structure of a 27-kilodalton methylcobalamin-containing fragment of methionine synthase from Escherichia coli was determined at 3.0 Å resolution. This structure depicts cobalamin-protein interactions and reveals that the corrin macrocycle lies between a helical amino-terminal domain and an α/β carboxyl-terminal domain that is a variant of the Rossmann fold. Methylcobalamin undergoes a conformational change on binding the protein; the dimethylbenzimidazole group, which is coordinated to the cobalt in the free cofactor, moves away from the corrin and is replaced by a histidine contributed by the protein. The sequence Asp-X-His-X-X-Gly, which contains this histidine ligand, is conserved in the adenosylcobalamin-dependent enzymes methylmalonyl-coenzyme A mutase and glutamate mutase, suggesting that displacement of the dimethylbenzimidazole will be a feature common to many cobalamin-binding proteins. Thus the cobalt ligand, His 759 , and the neighboring residues Asp 757 and Ser 810 , may form a catalytic quartet, Co-His-Asp-Ser, that modulates the reactivity of the B 12 prosthetic group in methionine synthase.

Porphyrias

2010-03-01

Hervé Puy , Laurent Gouya , Jean‐Charles Deybach

THE JOURNAL OF BIOLOGICAL CHEMISTRY.

1905-11-25

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Multienzyme complexes

1974-02-01

Lester J. Reed

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMultienzyme complexesLester J. ReedCite this: Acc. Chem. Res. 1974, 7, 2, 40–46Publication Date (Print):February 1, 1974Publication History Published online1 May 2002Published inissue 1 February 1974https://doi.org/10.1021/ar50074a002RIGHTS & PERMISSIONSArticle … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMultienzyme complexesLester J. ReedCite this: Acc. Chem. Res. 1974, 7, 2, 40–46Publication Date (Print):February 1, 1974Publication History Published online1 May 2002Published inissue 1 February 1974https://doi.org/10.1021/ar50074a002RIGHTS & PERMISSIONSArticle Views996Altmetric-Citations641LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-Alerts Get e-Alerts

Enzymic determination of <scp>d</scp>(−)-β-hydroxybutyric acid and acetoacetic acid in blood

1962-01-01

D H Williamson , John Mellanby , HA Krebs

Research Article| January 01 1962 Enzymic determination of d(−)-β-hydroxybutyric acid and acetoacetic acid in blood DH WILLIAMSON; DH WILLIAMSON Search for other works by this author on: This Site PubMed … Research Article| January 01 1962 Enzymic determination of d(−)-β-hydroxybutyric acid and acetoacetic acid in blood DH WILLIAMSON; DH WILLIAMSON Search for other works by this author on: This Site PubMed Google Scholar J MELLANBY; J MELLANBY Search for other works by this author on: This Site PubMed Google Scholar HA KREBS HA KREBS Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1962) 82 (1): 90–96. https://doi.org/10.1042/bj0820090 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation DH WILLIAMSON, J MELLANBY, HA KREBS; Enzymic determination of d(−)-β-hydroxybutyric acid and acetoacetic acid in blood. Biochem J 1 January 1962; 82 (1): 90–96. doi: https://doi.org/10.1042/bj0820090 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1962 The Biochemical Society1962 Article PDF first page preview Close Modal You do not currently have access to this content.

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Homogeneous Catalysis with Metal Phosphine Complexes

1983-01-01

L. H. Pignolet

The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. 1893.

1991-01-01

WILLIAM B. COLEY

William Bradley Coley (Fig. I) stemmed from old New England stock. After graduating from Yale in 1884. Coley spent two years in Portland, Oregon, teaching Latin and Greek before entering … William Bradley Coley (Fig. I) stemmed from old New England stock. After graduating from Yale in 1884. Coley spent two years in Portland, Oregon, teaching Latin and Greek before entering Harvard Medical School. After completing a competitive examination, he became an intern at the New York Hospital

Sunscreen and Photoprotection Habits for Patients With Porphyria and Non‐Porphyric Photosensitivity Conditions

2025-06-23

David Bajek , R.S. Dawe , Ewan Eadie +2 more | Photodermatology Photoimmunology & Photomedicine

ABSTRACT Background/Objectives Individuals with photosensitivity diseases, including porphyria, face significant challenges in managing their condition due to heightened sensitivity to ultraviolet (UV) and visible light. Comprehensive photoprotection strategies are essential … ABSTRACT Background/Objectives Individuals with photosensitivity diseases, including porphyria, face significant challenges in managing their condition due to heightened sensitivity to ultraviolet (UV) and visible light. Comprehensive photoprotection strategies are essential and prioritize environmental modifications, behavioral adjustments, protective clothing, and hats. Sunscreens serve as a supplementary measure, particularly for exposed skin areas not otherwise protected. However, the extensive variety of available sunscreen products and limited guidance on their efficacy complicate the selection process. This study evaluates sunscreen use among photosensitive individuals and gathers feedback to inform future service development and research. Methods A questionnaire was completed by 32 individuals with porphyria (mostly with porphyrias causing skin photosensitivity) and 50 individuals with non‐porphyric photosensitivity conditions, totaling 82 participants. The survey assessed preferences and experiences with sunscreens, focusing on criteria such as protection efficacy, cost, availability, and ease of use. Responses were analyzed to identify trends and challenges in integrating sunscreens into broader photoprotection strategies. Results Protection efficacy was the primary factor influencing sunscreen choice among photosensitive patients, highlighting its importance alongside other photoprotection measures. The survey revealed considerable variation in sunscreen use. La Roche‐Posay was the most favored brand. While 56% of porphyria patients used sunscreens explicitly labelled for visible light protection, only 11% of non‐porphyric patients did so. Overall, 40% of participants reported issues with sunscreens, and approximately half expressed dissatisfaction with certain products, emphasizing the need for more effective and user‐friendly options. Conclusions Sunscreens are a critical adjunct to broader photoprotection strategies for photosensitive patients but are not a standalone solution. Particularly for those with porphyrias, effectiveness was regarded as especially important. The variability in product preferences and the frequent difficulties reported highlight the need for improved guidance and accessibility of sunscreens tailored to diverse photosensitivity needs. Future research should focus on developing clear recommendations and expanding options to ensure effective and personalized photoprotection.

Comparative effectiveness of human hematin and heme arginate in the management of porphyria attacks: an observational study across three hospitals in Colombia

2025-06-22

Enyd-E Rave-B , N.A. Rojas-Henao , Andrés Felipe Valencia Quintero +1 more | Hospital Practice

Porphyria is an orphan disease classified as a genetic disorder caused by a partial or high-grade deficiency of enzymes involved in the synthesis of heme, an essential component of hemoglobin. … Porphyria is an orphan disease classified as a genetic disorder caused by a partial or high-grade deficiency of enzymes involved in the synthesis of heme, an essential component of hemoglobin. This deficiency results in the accumulation of porphyrins (ALAS1 and PBG), intermediates in the heme metabolic pathway. This accumulation triggers porphyria attacks. In Colombia the Heme Arginate and Human Hematin are the therapeutics alternatives for the management of porphyria Attacks. To evaluate the comparative effectiveness of heme arginate versus human hemin for treating porphyria attacks in hospitalized patients across three institutions in Medellin, Colombia. An observational and analytical study was conducted to compare the outcomes of treatment with human hematin versus heme arginate in clinical episodes of patients diagnosed with porphyria between 2015-2021. In episodes treated with heme arginate (ArgH), 75% achieved pain control or reduction, 41.6% showed a reduction in opioid dosage, and 88.8% achieved resolution of the Porphyria attack. For episodes treated with human hematin (HH), 85.3% achieved pain control or reduction, 53.6% showed a reduction in opioid dosage, and 90.2% achieved resolution of the attack. When evaluating the effectiveness of both treatments, no statistically significant differences were observed across the three predefined effectiveness outcomes of the study. This study provides a comparative evaluation of heme arginate (ArgH) and human hematin (HH) in the management of Porphyria attacks, demonstrating that both treatments are similarly effective in achieving pain control, reducing opioid use, and resolving clinical attacks.

Atypical Presentation of Homozygous UROD Mutation: Porphyria Cutanea Tarda or Mild Hepatoerythropoietic Porphyria?

2025-06-19

Pedro Gabriel Dotto , Mônica Ribeiro de Azevedo Vasconccellos , José Francisco da Silva Franco +2 more | PubMed

We report a patient homozygous for the UROD c.185C>T (p.P62L) variant who presents with clinical features resembling familial porphyria cutanea tarda (PCT). This case highlights the limitations of rigid UROD-related … We report a patient homozygous for the UROD c.185C>T (p.P62L) variant who presents with clinical features resembling familial porphyria cutanea tarda (PCT). This case highlights the limitations of rigid UROD-related porphyria classifications and supports the existence of a phenotypic continuum modulated by genetic, epigenetic, and environmental factors.

Eruption of Petechiae in Liver Failure in an 80-Year-Old Patient: A Case Report

2025-06-14

Abiola Z Odeyinka , Selene M Kizy , Liana N Ly +1 more | Cureus

The single-particle structures of a Bacterial Cyanide Dihydratase and a Fungal Cyanide Hydratase

2025-06-12

Santiago Justo Arévalo , Valeria Valle-Riestra-Felice , Maria José Barahona +4 more | bioRxiv (Cold Spring Harbor Laboratory)

Abstract Cyanide is widely used in industries due to its strong affinity for metals, a property that also underlies its potent toxicity. Industries therefore must reduce cyanide concentration in wastewater … Abstract Cyanide is widely used in industries due to its strong affinity for metals, a property that also underlies its potent toxicity. Industries therefore must reduce cyanide concentration in wastewater final disposal. Physical, chemical, and biological methods have been developed for this purpose; however, knowledge about the structure of enzymes involved in cyanide degradation remains limited. Structural characterization of these proteins could facilitate the development of more efficient enzymes with enhanced bioremediation potential. Here, we present the single-particle cryo-electron microscopy structures of a cyanide dihydratase from Bacillus safensis and a cyanide hydratase from Gloeocercospora sorghi at 2.2 Å and 2.0 Å resolution, respectively. We provide a comprehensive description and comparative analysis of these structures alongside all previously experimentally determined nitrilase structures. Importantly, our full-length structures reveal new structural features in the C-terminal as well as specific intermolecular interactions between protomer interfaces and within the helix lumen. Finally, our findings offer insights into the possible reaction mechanisms of these two enzymes.

Managing Psychosis in Acute Intermittent Porphyria: A Case Report on Olanzapine Use

2025-06-11

Cinly Ooi , Chao Tian Tang , Saskia Ting +2 more | Cureus

Porfiria cutánea tarda: manejo exitoso asociado a omisión de suplementación de hierro.

2025-06-09

Sofía Isea López , Ana María Sáenz , Elízabeth Ball | Dermatología Venezolana

La porfiria cutánea tarda (PCT) es una enfermedad ampollar que ocurre en áreas fotoexpuestas por deficiencia en la actividad de la enzima uroporfirinógeno descarboxilasa (UROD). El exceso de hierro es … La porfiria cutánea tarda (PCT) es una enfermedad ampollar que ocurre en áreas fotoexpuestas por deficiencia en la actividad de la enzima uroporfirinógeno descarboxilasa (UROD). El exceso de hierro es factor desencadenante en pacientes predispuestos. Se presenta el caso clínico de un paciente masculino de 62 años, con ampollas en dorso de manos, quien recibía tratamiento con hierro por antecedente de anemia hemolítica autoinmune. Discusión: La acumulación de hierro hepático puede llevar a la inhibición de la actividad de la UROD, provocando la acumulación de porfirinas en la piel y otros tejidos produciendo fotosensibilidad y síntomas característicos de la enfermedad. Conclusión: Los suplementos de hierro, mutaciones asociadas al gen del hierro y hemocromatosis son desencadenantes de PCT. El manejo multidisciplinario es esencial para optimizar la conducta y prevenir complicaciones a largo plazo.

Clinical Features and Outcomes of Acute Intermittent Porphyria Presenting With Acute Quadriparesis: A Case Series and Follow‐Up Study

2025-06-01

Reem Alhammad , Rema A Almutawa , Abdulrahman Ali +7 more | European Journal of Neurology

A retrospective case series of acute intermittent porphyria (AIP) presenting with acute quadriparesis is described with a focus on patterns of neuropathy and nerve conduction study findings. Six patients with … A retrospective case series of acute intermittent porphyria (AIP) presenting with acute quadriparesis is described with a focus on patterns of neuropathy and nerve conduction study findings. Six patients with acute polyneuropathy were diagnosed with AIP on the basis of characteristic clinical findings, urine porphobilinogen levels, and pathogenic variants in the hydroxymethylbilane synthase gene. Vital function impairment, neuropathic patterns, serial changes in nerve conduction studies (NCS), and laboratory findings are reviewed. A total of six patients with acute porphyric neuropathy were included. Patterns of weakness varied between upper and lower extremities. Three patients exhibited allodynia with preservation of large fiber sensory modalities in the acute polyneuropathy phase. Initial NCS revealed motor axonal polyneuropathy in four patients with sparing of motor conduction velocities and latencies. Relative sparing of tibial compound muscle action potential amplitudes is seen in two patients. Serial NCS revealed interval reduction of compound muscle action potential amplitudes in the upper extremity only in one patient and selective reduction of sensory nerve action potential amplitudes of the lower extremity in another patient. There were substantial delays in diagnoses, with all but one patient misdiagnosed as GBS. All but two patients required ambulation aids at last follow-up assessment. The findings in this series show variability in neuropathic patterns and NCS changes over time in AIP presenting with acute polyneuropathy. Small fiber neuropathy and allodynia with sparing of large fiber sensory modalities may serve as a diagnostic clue guiding early recognition of AIP in patients presenting with acute polyneuropathy.

Efavirenz-induced heme protein induction and coproporphyrin levels: Insights from in vitro experiments and in vivo studies

2025-06-01

Leila Potzel , Jonny Kinzi , Isabell Seibert +3 more | Drug Metabolism and Pharmacokinetics

Dark ocean archaeal and bacterial chemoautotrophs drive vitamin B1 production in oxygen minimum zones

2025-05-31

Kristin Bergauer , Christopher P. Suffridge , Fabian Wittmers +3 more | ISME Communications

Structural Study of Enzymes Involved in Porphyrin Metabolism

2025-05-31

Masakazu Sugishima | Nihon Kessho Gakkaishi

Myopathy, lactic acidosis and sideroblastic anemia syndrome 1 (MLASA1) : clinical hallmarks in a large pedigree with a novel PUS1 R144Q mutation, remarkable response to somatropin, and review of the literature

2025-05-29

Lucia Parisi , Robert Escher | Haematologica

Not available. Not available.

Comparison of Pyrazinamide with Isoniazid for Their Effects on the Heme Biosynthetic Pathway in Mouse Liver

2025-05-28

Fu‐Ying Qin , Ruizhi Gu , Jiaojiao Zhang +4 more | Metabolites

Background/Objectives: Isoniazid (INH) and pyrazinamide (PZA) are first-line drugs used to treat tuberculosis (TB), but their use is generally contraindicated in patients with porphyria, a group of metabolic disorders caused … Background/Objectives: Isoniazid (INH) and pyrazinamide (PZA) are first-line drugs used to treat tuberculosis (TB), but their use is generally contraindicated in patients with porphyria, a group of metabolic disorders caused by defects in the heme biosynthetic pathway. To investigate the basis for these contraindications, we compared the effects of INH and PZA on the heme biosynthetic pathway in mouse liver. Method: We investigated the hepatic expression and activity of the key enzymes involved in the heme biosynthetic pathway, including aminolevulinic acid synthase 1 (Alas1) and ferrochelatase (Fech). Additionally, we employed a metabolomic approach to analyze liver and fecal samples from the mice treated with INH or PZA. Result: We found that INH, but not PZA, significantly upregulated the expression and activity of Alas1, the rate-limiting enzyme in heme biosynthesis, while concurrently downregulating Fech, which converts protoporphyrin IX (PPIX) to heme. These changes resulted in the accumulation of the toxic intermediate aminolevulinic acid (ALA) and PPIX in the liver of INH-treated mice. In contrast, PZA had no measurable effect on the expression or function of Alas1 or Fech. Conclusions: These findings provide mechanistic insight into INH-induced porphyria exacerbation and suggest that PZA may not carry the same risk, challenging its current contraindication.

Construction and Modification of an Efficient Whole-Cell Catalyst for 5-Aminolevulinic Acid Using Induced Protoporphyrin IX as a Marker

2025-05-27

Hongfei Su , Shijing Chen , Xiaolin Chen +3 more

5-Aminolevulinic acid (5-ALA) is a high-value and high-demand functional amino acid. The exploration of engineering approaches for biosynthesis using whole-cell catalysts as a promising production strategy is often limited by … 5-Aminolevulinic acid (5-ALA) is a high-value and high-demand functional amino acid. The exploration of engineering approaches for biosynthesis using whole-cell catalysts as a promising production strategy is often limited by the lack of high-throughput evaluation platforms. Therefore, this study explored the correlative relationship between the fluorescence properties of 5-ALA-induced protoporphyrin IX (PpIX) and 5-ALA production in Escherichia coli (E. coli). Then, as a high-throughput screening platform, the expression of key genes hemAC5 and hemL was balanced, and the favorable mutation strategy of the key enzyme GluTR was explored. In addition, the efficiency of 5-ALA synthesis was improved by "transferring" and "throttling" of downstream metabolism. Finally, the engineered strain MGRΔBGTG yielded 1.494 g/L in a 5 L fermenter. This work provided a new indirect evaluation method for constructing the 5-ALA whole-cell catalyst capacity and a mining model for engineering approaches.

OATP1B1/1B3 deficiency exacerbates hyperbilirubinemia in erythropoietic protoporphyria

2025-05-27

Ruizhi Gu , Fu‐Ying Qin , Luxuan Wang +7 more

Erythropoietic protoporphyria (EPP) is caused by loss-of-function mutations in ferrochelatase (FECH), leading to the accumulation of its substrate, protoporphyrin IX (PPIX). PPIX is primarily produced in the bone marrow and … Erythropoietic protoporphyria (EPP) is caused by loss-of-function mutations in ferrochelatase (FECH), leading to the accumulation of its substrate, protoporphyrin IX (PPIX). PPIX is primarily produced in the bone marrow and transported to the liver for excretion. Because PPIX is hydrophobic, its elevated levels can cause bile duct blockage, cholestatic liver injury, and even liver failure. However, the specific transporter responsible for PPIX uptake into hepatocytes remains unclear. The OATP1B1/1B3 transporters, which are expressed in hepatocytes, facilitate the uptake of coproporphyrin III, a structural analog of PPIX. Additionally, OATP1B1/1B3 mediates the uptake of bilirubin, a biomarker of liver injury, from plasma into the liver for excretion. Therefore, we aimed to determine the role of OATP1B1/1B3 in regulating PPIX and bilirubin homeostasis under EPP conditions. A mouse strain carrying a Fech mutation was used as an EPP model. Building on this, we generated a new EPP mouse model with Oatp1a/1b deficiency. Using these EPP mouse models, along with OATP1B1/1B3-overexpressing cells, our study revealed that PPIX is not a substrate of OATP1B1/1B3. Notably, our work found that genetic deficiency or pharmacologic suppression of Oatp1a/1b exacerbates hyperbilirubinemia in EPP mice without worsening liver injury. Mechanistically, Oatp1a/1b deficiency impairs bilirubin uptake from plasma, while Fech deficiency leads to PPIX-mediated bile duct blockage and reduced bilirubin excretion, synergistically exacerbating hyperbilirubinemia. In summary, our work demonstrated that deficiency or suppression of Oatp1a/1b exacerbates hyperbilirubinemia in EPP mouse models, suggesting that assessment of OATP1B1/1B3 function is crucial in EPP patients with EPP with hyperbilirubinemia. SIGNIFICANCE STATEMENT: This work revealed that serum bilirubin levels are not paralleled with liver damage in the erythropoietic protoporphyria mouse models with Oatp1a/1b deficiency. Our findings suggest that assessment of OATP1B1/1B3 function is crucial in patients with erythropoietic protoporphyria with hyperbilirubinemia.

Sporadic Porphyria Cutanea Tarda, Cutaneous Sarcoidosis, and Compound Heterozygosity of HFE Mutations Cys282Tyr and His63Asp—A Case Report

2025-05-27

Jowon L. Kim , Richard I. Crawford , Ian Marie Lano +1 more

ABSTRACT Porphyria cutanea tarda (PCT) is caused by inherited or acquired defects of uroporphyrinogen decarboxylase (UROD) in the heme biosynthetic pathway. Altered iron homeostasis via hemochromatosis gene (HFE) mutations is … ABSTRACT Porphyria cutanea tarda (PCT) is caused by inherited or acquired defects of uroporphyrinogen decarboxylase (UROD) in the heme biosynthetic pathway. Altered iron homeostasis via hemochromatosis gene (HFE) mutations is one of many susceptibility factors associated with the sporadic form of PCT. Though sarcoidosis is not commonly associated with PCT, prior reports of hepatic sarcoidosis postulated that hepatic granulomas affect UROD activity by direct interference or immunological mechanisms. Here we describe a case of acquired PCT in the setting of (HFE):c.845G>A (p.Cys282Tyr) and (HFE):c.187C>G (p.His63Asp) compound heterozygosity, hepatic steatosis, and cutaneous sarcoidosis.

A Rare Case of Progressive Bulbar Palsy of Childhood

2025-05-26

B. Sudhakara Reddy , N. Veena , Naveen Kumar +1 more

Compartmentalization of heme biosynthetic pathways into yeast mitochondria enhances heme production

2025-05-22

Jae Yoon Won , Hyun-Jae Lee , Eun Yoon +2 more

Saccharomyces cerevisiae is a generally recognized as safe (GRAS) workhorse strain widely used in the food industry for the cost-effective production of food ingredients. However, the heme production yield in … Saccharomyces cerevisiae is a generally recognized as safe (GRAS) workhorse strain widely used in the food industry for the cost-effective production of food ingredients. However, the heme production yield in yeast is significantly lower than in bacteria for two main reasons: (1) the heme biosynthetic pathway is bifurcated into the cytosol and mitochondria, and (2) yeast's heme biosynthetic protoporphyrin-dependent (PPD) pathway is thermodynamically unfavorable compared with bacteria's coproporphyrin-dependent (CPD) pathway. To overcome these limitations, the PPD and CPD pathways were compartmentalized into the mitochondria by attaching mitochondria-targeting sequences (MTSs) to the N-terminus of the enzymes. All the enzyme activities required for the CPD pathway are present in S. cerevisiae, except for copro-heme decarboxylase (HemQ); therefore, bacterial HemQ with the N-terminal MTS was introduced to complete the CPD pathway. The resulting S. cerevisiae H4+MTS9HemQCg strain with mitochondrial PPD and CPD pathways showed 65% higher heme concentration than the engineered strain with only the mitochondrial PPD pathway. Furthermore, the functional expression level of HemQ from Corynebacterium glutamicum was significantly enhanced in vitro and in vivo by the co-expression of Group-I HSP60 chaperonins (GroEL and GroES) derived from Escherichia coli. The engineered S. cerevisiae H4+MTS9HemQCg+GroELS strain containing the mitochondrial PPD and CPD pathways and the Group-I HSP60 chaperonins produced the highest heme concentration (4.6 mg/L), which was 17% higher than that produced by the H4+MTS9HemQCg strain.

A Triple Threat: Acute Intermittent Porphyria Presenting with SIADH and Hypertensive Encephalopathy in a Child: A Case Report

2025-05-19

Muhammad Ilyas Khan

X‐Linked Sideroblastic Anaemia Caused by Intronic ALAS2 Variant Resulting in Highly Variable Expressive Phenotype in Male Siblings, a Case Report

2025-05-19

James A. O’Connor , Niall Mannion , Caoimhe McKenna +2 more

ABSTRACT X‐linked sideroblastic anaemia (XLSA) is a rare hereditary disorder caused by mutations in the ALAS2 gene, essential for haem biosynthesis. We report two male siblings, the first of whom … ABSTRACT X‐linked sideroblastic anaemia (XLSA) is a rare hereditary disorder caused by mutations in the ALAS2 gene, essential for haem biosynthesis. We report two male siblings, the first of whom developed severe microcytic hypochromic anaemia requiring regular transfusions, iron chelation and an allogeneic bone marrow transplant, while his brother displayed only mild microcytic hypochromic indices without anaemia. Initial genetic screening did not identify a pathogenic variant. However, duo exome sequencing later revealed an intronic ALAS2 mutation, initially categorised as of uncertain significance and subsequently reclassified as pathogenic. This case underscores the diagnostic challenges posed by intronic mutations and the highly variable expressivity of XLSA, even among siblings. Trial Registration : The authors have confirmed clinical trial registration is not needed for this submission.

Prévalence de la porphyrie hépatique aiguë en population française : premiers résultats de l’étude prospective PrevPHA

2025-05-16

R. Jaussaud , P. Mercié , Laurent Alric +7 more

Porphyria Cutanea Tarda: A Phenotypic Expression of Several Genes

2025-05-12

Sebastián J Vázquez-Folch , Gabriel A Jiménez-Berríos , Natalio Izquierdo +1 more

Aminolevulinic-acid

2025-05-09

A case with porphyria presenting with episodic hypertension and tachycardia mimicking pheochromocytoma

2025-05-09

Haşlak Gokce Velioğlu , Ayşe Ağbaş , Yavuz Karabağ +6 more

Acute Hepatic Porphyria vs. Guillain-Barré Syndrome: Response to “Axonal Neuropathy in Hepatic Porphyria Should Not be Confused With Guillain-Barre Syndrome”

2025-05-08

Ashok Kumar Pannu

Vitamin B12-Functionalized NiMn2O4 Spinel: A Promising Bioinspired Electrocatalyst for Dechlorination in the Aqueous Phase

2025-05-07

Jun Duan , Yaqi Yang , Shiying Fan +2 more

Efficacy and safety of givosiran in Japanese patients with acute hepatic porphyria: clinical findings from an expanded access study

2025-05-02

Nobuaki Ozaki , Yoshie Goto , Norihisa Fujii +4 more

Acute hepatic porphyria (AHP), a rare genetic disorder, causes life-threatening porphyria attacks and chronic pain and impairs daily functioning and quality of life. Recently, a new siRNA therapy, givosiran, became … Acute hepatic porphyria (AHP), a rare genetic disorder, causes life-threatening porphyria attacks and chronic pain and impairs daily functioning and quality of life. Recently, a new siRNA therapy, givosiran, became available for AHP. This open-label, multicenter, single-arm study expanded access to givosiran and further explored its safety and efficacy in 10 Japanese patients with AHP. Participants received monthly subcutaneous injections of givosiran (2.5 mg/kg). Three patients were continued from the phase III ENVISION study of givosiran, and seven were newly recruited. Assessments comprised clinical AHP features, urinary aminolevulinic acid (ALA) and porphobilinogen (PBG) levels, use of hemin to treat attacks, and the Givosiran Patient Experience Questionnaire (GPEQ). Urinary ALA and PBG levels remained at or below upper limits of normal levels throughout the study. The GPEQ showed symptomatic improvement in eight participants. Of the eight adverse events, five were deemed by the investigator to be related to givosiran. One patient experienced two attacks, which required urgent healthcare visits but no hemin use. Generally, the safety profile was consistent with that previously observed. All adverse events were nonserious, and no deaths occurred. The study indicates that monthly givosiran administration is safe and clinically useful in Japanese patients with AHP.

Biological Variation of Erythrocyte Total, Metal-Free, and Zinc Protoporphyrin IX in Patients with Erythropoietic Protoporphyria and Healthy Subjects: Implications for Clinical Interpretation and Monitoring

2025-05-02

Paul Kjetel Soldal Lillemoen , Pernille Kjeilen Fauskanger , Sverre Sandberg +1 more

Abstract Background There is a lack of robust biological variation (BV) data for porphyria-related biomarkers. Our study aimed to estimate BV of erythrocyte total, metal-free, and zinc protoporphyrin IX in … Abstract Background There is a lack of robust biological variation (BV) data for porphyria-related biomarkers. Our study aimed to estimate BV of erythrocyte total, metal-free, and zinc protoporphyrin IX in patients with erythropoietic protoporphyria (EPP) and healthy subjects and to explore the clinical implications of these data. Methods Fourteen patients with EPP and 15 healthy subjects were sampled quarterly for 2 years, and erythrocyte protoporphyrin analyses were performed in duplicate in all samples. A Bayesian method was used to estimate the within-subject (CVI) and personal (CVP(i)) BV. Results Based on clinical and laboratory assessments, EPP patients were stable during the study, with only 2 data points excluded. CVI in the EPP cohort was estimated as 9.8% (95% credible interval 8.5%–11.5%) for erythrocyte total protoporphyrin, 10.5% (9.0%–12.3%) for metal-free protoporphyrin, and 5.9% (4.3%–8.0%) for zinc protoporphyrin. Baseline metal-free protoporphyrin ranged from 6.9 to 139.8 µmol/L, but the CVP(i)s derived for each patient were similar (20th and 80th percentile of predicted distribution 9.5%–11.5%), and data were homogeneously distributed. Metal-free protoporphyrin was not measurable in the healthy cohort. Data for zinc protoporphyrin were heterogeneously distributed in both study cohorts. Conclusions The EPP patients had different set points for metal-free protoporphyrin, but the CVP(i) was similar, supporting the use of the same treatment goals when monitoring. This study is the first to use Bayesian analysis to demonstrate that personal BV is similar in patients with stable, chronic disease and different set points.

A Case with Bilateral C-shaped Autofluorescence in Retinal Degeneration

2025-05-01

Hueih‐Shing Hsu , Chunya Kang , Eugene Yu‐Chuan Kang +1 more

Unique Dermatological and Systemic Manifestations in a Classic Pediatric Case of Kindler Syndrome: A Case Report and Literature Review

2025-05-01

Muhammad Salman Aamir , Fahad Faizullah , Malik Waleed Zeb Khan +2 more | Clinical Medicine Insights Case Reports

Kindler Syndrome (KS) is a rare, autosomal recessive genodermatosis caused by mutations in the FERMT1 gene, leading to skin fragility, blistering, photosensitivity, and progressive poikiloderma. We present a unique case … Kindler Syndrome (KS) is a rare, autosomal recessive genodermatosis caused by mutations in the FERMT1 gene, leading to skin fragility, blistering, photosensitivity, and progressive poikiloderma. We present a unique case of KS in a 6-year-old boy born to consanguineous parents, exhibiting uncommon dermatological, and systemic features. The patient developed multiple erythematous plaques, hemorrhagic crusting, and purulent discharge after birth, with a family history suggesting genetic predisposition. Uniquely, the patient presented with well-demarcated hyperpigmented macules on the abdomen, a feature rarely seen in KS, which adds to the phenotypic diversity of the condition. Additionally, the patient had extensive lanugo hair growth, nail dystrophy, and gingivitis, typical of KS, but without urinary or mucosal involvement, a departure from more classic presentations. The patient also presented with glucose intolerance, indicated by elevated glucose levels of 222 mg/dL, likely due to infection-induced metabolic dysregulation, which normalized after treatment. The differential diagnosis initially considered porphyria cutanea tarda (PCT) due to overlapping features like photosensitivity and skin fragility. However, laboratory findings, including normal liver function and the absence of specific PCT markers, effectively excluded PCT. Microbiological swabs from purulent discharge identified Staphylococcus aureus, which was sensitive to the prescribed antibiotics. Management focused on symptomatic relief with antibiotics, supportive care, and iron supplementation to address anemia caused by chronic skin erosions. The case highlights diagnostic challenges in resource-limited settings where genetic testing was unavailable. It underscores the need for heightened awareness of atypical KS manifestations, the importance of clinical evaluation and genetic counseling, and contributes to the expanding knowledge of KS, particularly in populations with consanguineous marriages.

Unexpected presentation of a first episode of acute hepatic porphyria (AHP) presenting with severe hyponatremia, seizure, severe rhabdomyolysis, arterial hypertension and posterior reversible encephalopathy syndrome (PRES) in a female adolescent

2025-05-01

S. Welcker , F Quittek , A Hellenschmidt +6 more

Abstract 1496 Functional Characterization of a Diiron Protein: Unraveling its Role in Methanogen Oxidative Stress Response

2025-05-01

Amit Rai , Neelima Bhatt , Jin Xiong +6 more | Journal of Biological Chemistry

Abstract 1764 Uncovering the role of protein structure and dynamics in the regulation of heme biosynthesis

2025-05-01

Bethany Brown | Journal of Biological Chemistry

Abstract 1089 Pseudomonas aeruginosa PA1790 is a novel heme-degrading ferritin family hydroxylase

2025-05-01

Erin Higgins , Sampriti Mukherjee | Journal of Biological Chemistry

Abstract 3036 The terminal heme synthetic enzyme, Coproheme Decarboxylase, coordinates Mycobacterial heme synthesis and scavenging

2025-05-01

Amit R. Reddi , Yibo Fu , Rebecca K. Donegan | Journal of Biological Chemistry

Abstract 1172 Insights into heme binding and transport in bacterial cytochrome c biogenesis

2025-05-01

Molly C. Sutherland , Alicia N. Kreiman , Tania Yeasmin | Journal of Biological Chemistry

Cimetidine (H2 histamine antagonist), Fexofenadine (H1 histamine antagonist), and Zinc sulphate in the treatment of erythropoietic protoporphyria

2025-05-01

Hans Christian Wulf , Peter A. Philipsen , Catharina M. Lerche

Erythropoietic protoporphyria (EPP) patients are deficient in the ferrochelatase enzyme which converts protoporphyrin IX (PpIX) into heme, causing PpIX to accumulate in mature erythrocytes and skin. When skin is exposed … Erythropoietic protoporphyria (EPP) patients are deficient in the ferrochelatase enzyme which converts protoporphyrin IX (PpIX) into heme, causing PpIX to accumulate in mature erythrocytes and skin. When skin is exposed to visible light, a phototoxic reaction occurs with clinical symptoms of erythema, pain, and edema. Cimetidine (H2 histamine antagonist) may inhibit the δ-aminolevulinic acid synthase, reducing the build-up of PpIX. Fexofenadine (H1 histamine antagonist) may reduce histamine release and associated phototoxicity symptoms. Zinc sulphate, by inhibiting the formation of reactive oxygen species, may lessen exposure-related pain. Thirty-two EPP patients were treated for 68 summer seasons with Cimetidine, Fexofenadine, or Zinc sulphate. Primary outcome was the effect on PpIX levels. Treatment effects were registered in a quality-of-life questionnaire, including hours spent outdoors, time to sun induced skin pain, and maximal seasonal pain compared to a control year without treatment. Sun protection habits were also investigated. Our EPP patients had significant clinical improvement on Cimetidine or Zinc sulphate monotherapy. Fexofenadine had no significant effect. Combining Cimetidine with Zinc sulphate lowered PpIX levels by 5.7%, and 94% of patients taking Cimetidine and Zinc sulphate reported an 80% increase in time spent outdoors. Time to symptom onset was prolonged by 92%, maximal pain intensity was reduced by 29%, and quality of life improved by 36%. Combination therapy with Cimetidine and Zinc sulphate is a safe, well tolerated, effective, low-cost treatment for EPP patients. Quality of life is improved, time to sun induced symptoms is prolonged, and pain is reduced.