Porphyrinogens which are intermediates in the heme biosynthesis. They have four methyl and four propionic acid side chains attached to the pyrrole rings. Coproporphyrinogens I and III are formed in the presence of uroporphyrinogen decarboxylase from the corresponding uroporphyrinogen. They can yield coproporphyrins by autooxidation or protoporphyrin by oxidative decarboxylation.
Transcriptional control of Bacillus subtilis hemN and hemZ. (1/25)Previous characterization of Bacillus subtilis hemN, encoding a protein involved in oxygen-independent coproporphyrinogen III decarboxylation, indicated the presence of a second hemN-like gene (B. Hippler, G. Homuth, T. Hoffmann, C. Hungerer, W. Schumann, and D. Jahn, J. Bacteriol. 179:7181-7185, 1997). The corresponding hemZ gene was found to be split into the two potential open reading frames yhaV and yhaW by a sequencing error of the genome sequencing project. The hemZ gene, encoding a 501-amino-acid protein with a calculated molecular mass of 57,533 Da, complemented a Salmonella typhimurium hemF hemN double mutant under aerobic and anaerobic growth conditions. A B. subtilis hemZ mutant accumulated coproporphyrinogen III under anaerobic growth conditions. A hemN hemZ double mutant exhibited normal aerobic and anaerobic growth, indicating the presence of a third alternative oxygen-independent enzymatic system for coproporphyrinogen III oxidation. The hemY gene, encoding oxygen-dependent protoporphyrinogen IX oxidase with coproporphyrinogen III oxidase side activity, did not significantly contribute to this newly identified system. Growth behavior of hemY mutants revealed the presence of an oxygen-independent protoporphyrinogen IX oxidase in B. subtilis. A monocistronic hemZ mRNA, starting 31 bp upstream of the translational start codon, was detected. Reporter gene fusions of hemZ and hemN demonstrated a fivefold anaerobic induction of both genes under nitrate ammonifying growth conditions. No anaerobic induction was observed for fermentatively growing B. subtilis. The B. subtilis redox regulatory systems encoded by resDE, fnr, and ywiD were indispensable for the observed transcriptional induction. A redox regulation cascade proceeding from an unknown sensor via resDE, through fnr and ywiD to hemN/hemZ, is suggested for the observed coregulation of heme biosynthesis and the anaerobic respiratory energy metabolism. Finally, only hemZ was found to be fivefold induced by the presence of H(2)O(2), indicating further coregulation of heme biosynthesis with the formation of the tetrapyrrole enzyme catalase. (+info)
Porphyria variegata and porphyria cutanea tarda in siblings: chemical and genetic aspects. (2/25)A woman aged 54 was studied because of a severe acute porphyric (neurologic) relapse with clinical and chemical findings characteristic of porphyria variegata. During a family survey, her brother, aged 59, was found to have chemical abnormalities typical of porphyria cutanea tarda, without suggestion of neurologic manifestations. He had mild skin changes compatible with either of these forms of porphyria. The sister exhibited the protocoproporphyria of porphyria variegata, together with a large amount of fecal "x" porphyrin fraction, without demonstrable isocoproporphyrins. The brother had a uro-isocopro-type of porphyria in accord with the diagnosis of porphyria cutanea tarda, and quite at variance with the sister's findings. This occurrence of porphyria variegata and porphyria cutanea tarda in siblings is thus far unique. Certain hypotheses are considered in respect to genetic aspects of the differing prophyrias in this sibling pair. (+info)
A mouse model of familial porphyria cutanea tarda. (3/25)Approximately one-third of patients with porphyria cutanea tarda (PCT), the most common porphyria in humans, inherit a single mutant allele of the uroporphyrinogen decarboxylase (URO-D) gene. PCT associated with URO-D mutations is designated familial PCT. The phenotype is characterized by a photosensitive dermatosis with hepatic accumulation and urinary excretion of uroporphyrin and hepta-carboxylic porphyrins. Most heterozygotes for URO-D mutations do not express a porphyric phenotype unless hepatic siderosis is present. Hemochromatosis gene (HFE) mutations are frequently found when the phenotype is expressed. We used homologous recombination to disrupt one allele of murine URO-D. URO-D(+/-) mice had half-wild type (wt) URO-D protein and enzymatic activity in all tissues but did not accumulate hepatic porphyrins, indicating that half-normal URO-D activity is not rate limiting. When URO-D(+/-) mice were injected with iron-dextran and given drinking water containing delta-aminolevulinic acid for 21 days, hepatic porphyrins accumulated, and hepatic URO-D activity was reduced to 20% of wt. We bred mice homozygous for an HFE gene disruption (HFE(-/-)) to URO-D(+/-) mice, generating mice with the URO-D(+/-)/HFE(-/-) genotype. These animals developed a porphyric phenotype by 14 weeks of age without ALA supplementation, and URO-D activity was reduced to 14% of wt. These data indicate that iron overload alone is sufficient to reduce URO-D activity to rate-limiting levels in URO-D(+/-) mice. The URO-D(+/-) mouse serves as an excellent model of familial PCT and affords the opportunity to define the mechanism by which iron influences URO-D activity. (+info)
Kinetic studies of novel di- and tri-propionate substrates for the chicken red blood cell enzyme coproporphyrinogen oxidase. (4/25)Coproporphyrinogen oxidase is an important enzyme in heme biosynthesis and catalyses the sequential oxidative decarboxylation of propionates on the A and B rings of the porphyrinogen ring. The effects of substituents on the C and D rings have not been systematically evaluated for their effects on the kinetic constants, K(m) and V(max). A series of synthetic porphyrinogens have been tested for their ability to affect these kinetic constants for the chicken enzyme. The enzyme exhibited the largest V(max) when incubated with the authentic substrate and was clearly able to distinguish between various substituents on the C and D rings of the macrocycle. When co-incubated with substrate, the authentic product, protoporphyrinogen-IX, appears to inhibit coproporphyrinogen oxidase and this may have an important role in the regulation of this enzyme. Thus the model for the active site of this enzyme should be modified to take these factors into account. (+info)
The genes required for heme synthesis in Salmonella typhimurium include those encoding alternative functions for aerobic and anaerobic coproporphyrinogen oxidation. (5/25)Insertion mutagenesis has been used to isolate Salmonella typhimurium strains that are blocked in the conversion of 5-aminolevulinic acid (ALA) to heme. These mutants define the steps of the heme biosynthetic pathway after ALA. Insertions were recovered at five unlinked loci: hemB, hemCD, and hemE, which have been mapped previously in S. typhimurium, and hemG and hemH, which have been described only for Escherichia coli. No other simple hem mutants were found. However, double mutants are described that are auxotrophic for heme during aerobic growth and fail to convert coproporphyrinogen III to protoporphyrinogen IX. These mutant strains are defective in two genes, hemN and hemF. Single mutants defective only in hemN require heme for anaerobic growth on glycerol plus nitrate but not for aerobic growth on glycerol. Mutants defective only in hemF have no apparent growth defect. We suggest that these two genes encode alternative forms of coproporphyrinogen oxidase. Anaerobic heme synthesis requires hemN function, while either hemN or hemF is sufficient for aerobic heme synthesis. These phenotypes are consistent with the requirement of a well-characterized class of coproporphyrinogen oxidase for molecular oxygen. (+info)
Crystal structure of the oxygen-dependant coproporphyrinogen oxidase (Hem13p) of Saccharomyces cerevisiae. (6/25)Coproporphyrinogen oxidase (CPO) is an essential enzyme that catalyzes the sixth step of the heme biosynthetic pathway. Unusually for heme biosynthetic enzymes, CPO exists in two evolutionarily and mechanistically distinct families, with eukaryotes and some prokaryotes employing members of the highly conserved oxygen-dependent CPO family. Here, we report the crystal structure of the oxygen-dependent CPO from Saccharomyces cerevisiae (Hem13p), which was determined by optimized sulfur anomalous scattering and refined to a resolution of 2.0 A. The protein adopts a novel structure that is quite different from predicted models and features a central flat seven-stranded anti-parallel sheet that is flanked by helices. The dimeric assembly, which is seen in different crystal forms, is formed by packing of helices and a short isolated strand that forms a beta-ladder with its counterpart in the partner subunit. The deep active-site cleft is lined by conserved residues and has been captured in open and closed conformations in two different crystal forms. A substratesized cavity is completely buried in the closed conformation by the approximately 8-A movement of a helix that forms a lid over the active site. The structure therefore suggests residues that likely play critical roles in catalysis and explains the deleterious effect of many of the mutations associated with the disease hereditary coproporphyria. (+info)
Role of aspartate 400, arginine 262, and arginine 401 in the catalytic mechanism of human coproporphyrinogen oxidase. (7/25)Coproporphyrinogen oxidase (CPO) is the sixth enzyme in the heme biosynthetic pathway, catalyzing two sequential oxidative decarboxylations of propionate moieties on coproporphyrinogen-III forming protoporphyrinogen-IX through a monovinyl intermediate, harderoporphyrinogen. Site-directed mutagenesis studies were carried out on three invariant amino acids, aspartate 400, arginine 262, and arginine 401, to determine residue contribution to substrate binding and/or catalysis by human recombinant CPO. Kinetic analyses were performed on mutant enzymes incubated with three substrates, coproporphyrinogen-III, harderoporphyrinogen, or mesoporphyrinogen-VI, in order to determine catalytic ability to perform the first and/or second oxidative decarboxylation. When Asp400 was mutated to alanine no divinyl product was detected, but the production of a small amount of monovinyl product suggested the K(m) value for coproporphyrinogen-III did not change significantly compared to the wild-type enzyme. Upon mutation of Arg262 to alanine, CPO was again a poor catalyst for the production of a divinyl product, with a catalytic efficiency <0.01% compared to wild-type, including a 15-fold higher K(m) for coproporphyrinogen-III. The efficiency of divinyl product formation for mutant enzyme Arg401Ala was approximately 3% compared to wild-type CPO, with a threefold increase in the K(m) value for coproporphyrinogen-III. These data suggest Asp400, Arg262, and Arg401 are active site amino acids critical for substrate binding and/or catalysis. Possible roles for arginine 262 and 401 include coordination of carboxylate groups of coproporphyrinogen-III, while aspartate 400 may initiate deprotonation of substrate, resulting in an oxidative decarboxylation. (+info)
Identification of tetrapyrrole compounds excreted by Rhodobacter sphaeroides and sources of the methyl hydrogens of bacteriochlorophyll a biosynthesized by R. sphaeroides, based on 13C-NMR spectral analysis of coproporphyrin III tetramethyl ester. (8/25)Red-fluorescent tetrapyrrole compounds excreted by Rhodobacter sphaeroides into the culture broth were concluded to be coproporphyrinogen (Copro'gen) III and uroporphyrinogen (Uro'gen) I, based on the (13)C-NMR spectral identification of coproporphyrin (Copro) III tetramethyl ester and uroproporphyrin (Uro) I octamethyl ester. The sources of the methyl hydrogens of bacteriochlorophyll a were established by analysis of the (13)C-NMR spectra of (2)H,(13)C-Copro III tetramethyl ester chemically derived from (2)H,(13)C-Copro'gen III biosynthesized through the feeding of delta-amino[2-(13)C]levulinic acid (ALA) to R. sphaeroides in medium containing 50% (2)H(2)O. We confirmed the previous finding that one of the methyl hydrogens was derived from water in the medium during decarboxylation of four acetyl side chains of Uro'gen III to generate Copro'gen III. It was further shown that the other hydrogen atoms, previously reported to be derived from methylene hydrogens at C-2 of ALA, had been exchanged with hydrogen of water in the medium in the biosynthetic pathways leading from ALA to Copro'gen III. (+info)
hemN - Oxygen-independent coproporphyrinogen III oxidase - Thermosynechococcus vulcanus - hemN gene & protein
Involved in the heme and chlorophyll biosynthesis. Catalyzes the anaerobic oxidative decarboxylation of propionate groups of rings A and B of coproporphyrinogen III to yield the vinyl groups in protoporphyrinogen IX.
Characterization of coproporphyrinogen III oxidase in Plasmodium falciparum cytosol - [email protected]
A unique hybrid pathway has been proposed for de novo heme biosynthesis in Plasmodium falciparum involving three different compartments of the parasite, namely mitochondrion, apicoplast and cytosol. While parasite mitochondrion and apicoplast have been shown to harbor key enzymes of the pathway, there has been no experimental evidence for the involvement of parasite cytosol in heme biosynthesis. In this study, a recombinant P. falciparum coproporphyrinogen III oxidase (rPfCPO) was produced in E. coli and confirmed to be active under aerobic conditions. rPfCPO behaved as a monomer of 61 kDa molecular mass in gel filtration analysis. Immunofluorescence studies using antibodies to rPfCPO suggested that the enzyme was present in the parasite cytosol. These results were confirmed by detection of enzyme activity only in the parasite soluble fraction. Western blot analysis with anti-rPfCPO antibodies also revealed a 58 kDa protein only in this fraction and not in the membrane fraction. The cytosolic ...
SA RS08910 - AureoWiki
MetabolismBiosynthesis of cofactors, prosthetic groups, and carriersHeme, porphyrin, and cobalaminputative oxygen-independent coproporphyrinogen III oxidase (TIGR00539; EC 188.8.131.52; HMM-score: 12.3) ...
Oxygen-dependent coproporphyrinogen III oxidase superfamily (IPR036406) | InterPro | EMBL-EBI
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
RCSB PDB - 1R3Y: Uroporphyrinogen Decarboxylase in complex with coproporphyrinogen-III
As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Lenti-CMV-CPOX, LH856224 | Vigene Biosciences
Lentivirus with CMV promoter-driven expression of coproporphyrinogen oxidase (CPOX) in pLenti vector with puromycin selection and C-terminal Myc and FLAG tags.
Uroporphyrinogen Decarboxylase Activity of Human Tissues | Biochemical Society Transactions
Thank you for your interest in spreading the word about Biochemical Society Transactions.. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.. ...
Porphyrin metabolism | LAMP
Porphyrins are organic aromatic compounds composed of four pyrrole rings interconnected to each other and to the Fe2+ ion. Porphyrins are essential cofactors of many proteins including cytochrome proteins and haemoglobin and myoglobin in humans. The first step in the production of porphyrin in animals is the mitochondrial formation of delta-aminolevulinate from glycine and succinyl-CoA. In humans, this aminolevulinate is then transported to cytosol where the 4-step conversion into Coproporphyrinogen III occurs. The remaining processing of this intermediate to protoporphyrin IX and then to heme takes place in mitochondrion.. The cytochrome proteins in Plasmodium and Coccidian species such as Toxoplasma and Neospora require de novo synthesis of porphyrin. Although P. falciparum obtains heme from host haemoglobin digestion, it cannot utilise them for biosynthesis of its own porphyrin-containing proteins  and converts them to hemozoin . The enzymes of de novo heme biosynthesis in P. falciparum ...
UROPORPHYRINOGEN DECARBOXYLASE (Upg D), ERYTHROCYTES
Draw a full, green-top (heparin) tube and place on wet ice immediately. Specimen must arrive at Legacy Central Laboratory before 12 noon. Friday draws are not accepted ...
Perch Blog Example Archive Page
Following the highly anticipated Season 7 premier of Game of Thrones we found ourselves asking how did they get social media so right?. Industry Insights Read more ...
Uroporphyrinogen Decarboxylase, Washed Erythrocytes - Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog
The porphyrias are a group of inherited disorders resulting from enzyme defects in the heme biosynthetic pathway. Porphyria cutanea tarda (PCT) is the most common porphyria resulting from a partial deficiency of hepatocyte or erythrocyte uroporphyrinogen decarboxylase (UROD; see The Heme Biosynthetic Pathway in Special Instructions). PCT is classified into 3 subtypes. The most frequently encountered is type I, a sporadic or acquired form, typically associated with concomitant disease or other precipitating factors. Patients exhibit normal UROD activity in erythrocytes but decreased hepatic activity. This differs from type II PCT in which patients exhibit approximately 50% activity in both erythrocytes and hepatocytes. Type II accounts for about 20% of cases and is inherited in an autosomal dominant manner with low penetrance. Type III is a rare familial form seen in less than 5% of PCT cases. As in type I, patients with type III PCT have normal UROD activity in erythrocytes with decreased ...
Showing results for tags CBS. - ACN Latitudes Forums
Every time I try to discuss methylation with my DDs LLMD, he tells me not to worry about it b/c treating her lyme is the big focus. My gut tells me that I need to consider and address her methylation results, especially as we continue to detox during her lyme treatment. My DD is constantly in an emotionally restless state (we never know when were going to have a good or bad day). Her tics, rages, and ability to be and feel calm and present wax and wane with her medical treatment. Here are my concerns re: her 23 and me results: Detoxification: CPOX4- GT (1/2) CYP1A1- CT (1/2) CYPD2D ...
List of MeSH codes (D03)
... coproporphyrinogens MeSH D03.549.909.500.700.900 - uroporphyrinogens MeSH D03.549.909.500.725 - protoporphyrins MeSH D03.549. ... coproporphyrinogens MeSH D03.383.129.578.840.500.700.900 - uroporphyrinogens MeSH D03.383.129.578.840.500.725 - protoporphyrins ...
The coproporphyrinogens have the outermost hydrogen atoms of the core replaced by four methyl groups −CH 3 (M) and four ...
List of MeSH codes (D23)
... coproporphyrinogens MeSH D23.767.727.700.900 - uroporphyrinogens MeSH D23.767.727.725 - protoporphyrins MeSH D23.767.727.880 - ...
List of MeSH codes (D04)
... coproporphyrinogens MeSH D04.345.783.500.700.900 - uroporphyrinogens MeSH D04.345.783.500.725 - protoporphyrins MeSH D04.345. ...
... at the US National Library of Medicine Medical Subject Headings (MeSH) PubChem - Coproporphyrinogen III v t ... Coproporphyrinogens are tetrapyrroles with four propionic acid groups and an equal number of substituted methyls. ...
Coproporphyrinogens - Wikipedia
List of MeSH codes (D03) - Wikipedia
Human Metabolome Database: Showing metabocard for Uroporphyrin III (HMDB0000916)
Article abstract | Medical Science Monitor
Category:Pages using duplicate arguments in template calls - wikidoc
Shopping Page. Buy or upgrade website. - Healthmatics | Page 8
Rate limiting step porphyrin synthesis ppt: Enumeration
MH DELETED MN ADDED MN
No data available that match "coproporphyrinogens"
- Coproporphyrinogens are tetrapyrroles with four propionic acid groups and an equal number of substituted methyls. (wikipedia.org)
- The resultant products have methyl groups in place of acetate and are known as coproporphyrinogens, with coproporphyrinogen III being the important normal intermediate in heme synthesis. (reath.me)