Coproporphyrinogen oxidase

Wildlife toxicologists should be attuned to developments in human health mercury, as assays that have been used successfully on humans may be suitable or adaptable for other vertebrate species. Echeverria and co-workers (Echeverria et al. 2005, 2006 Heyer et al. 2006) have characterized a gene encoding coproporphyrinogen oxidase, a gene in the heme biosynthetic pathway. Polymorphism in this gene predicts differential response to elemental mercury exposure in human subjects. Plans to modify this assay for other mercury species in matrices from wildlife are under way. 

Echeverria D, Woods JS, Heyer NJ, Rohhnan D, Farin FM, Li T, Garabedian CE. 2006. The association between a genetic polymorphism of coproporphyrinogen oxidase, dental mercury exposure and neurobehavioral response in humans. Neurotoxicol Teratol 28 39-48. 

HeyerNJ, Bittner Jr AC, Echeverria D, Woods JS. 2006. A cascade analysis of the interaction of mercury and coproporphyrinogen oxidase (CPOX) polymorphism on the heme biosynthetic pathway and porphyrin production. Toxicol Lett 161 159-166. 

MONOPHENOL MONOOXYGENASE NITRITE REDUCTASE PHOTOSYSTEM I QUERCETIN 2,3-DIOXYGENASE SUPEROXIDE DISMUTASES COPROPORPHYRINOGEN OXIDASE... 

Affected enzyme ALA-dehy- dratase Hydroxymethyl-bilane synthase Uroporphyrinogen III synthase Uroporphyrinogen decarboxylase Coproporphyrinogen oxidase Protoporphyrinogen oxidase Ferrochelatase... 

Fig. 7.3.1 The heme synthesis pathway starts in the mitochondrion. The next four steps proceed in the cytosol. Coproporphyrinogen oxidase is in the intermembrane space of the mitochondrion, and the last two enzymes reside at the mitochondral matrix side of the inner membrane. The product heme represses the first and rate-limiting enzyme -aminolevulinic acid (5-ALA) synthase at transcription, during the translation step, and by its transport into the mitochondrion... 

An acute disease caused by a deficiency in coproporphyrinogen oxidase. 

The decarboxylated product, coproporphyrinogen (Fig. 16-5), enters the mitochondria and is acted upon by coproporphyrinogen oxidase, which oxidatively... 

Woods, J.S., Southern, M.R. (1989). Studies on the etiology of trace metal-induced porphyria effects of porphyrinogenic metals on coproporphyrinogen oxidase in rat liver and kidney. Toxicol. Appl. Pharmacol. 91. 183-90. 

Figure 3 The synthesis of heme from glycine and sucdnyl-CoA. The enzymes are ALAS, S-aminolevulinic acid (ALA) synthase ALAD, S-aminolevulinic acid dehydratase PBGD, porphobilinogen deaminase UROIIIS, uroporphyrinogen III synthase UROD, uroporphyrinogen decarboxylase CPO, coproporphyrinogen oxidase PPO, protoporphyrinogen oxidase and FECH, ferrochelatase.

Protoporphyrinogen oxidase converts protoporphyrinogen IX to the fully desaturated porphyrin in a reaction that uses O2 as the terminal electron acceptor (Fig. 3). The crystal structure of the homodimeric enzyme shows it has one FAD per monomer, which presumably mediates the porphyrin oxidation reaction (19). Like the decarboxylation mediated by coproporphyrinogen oxidase, this reaction also occurs in the mitochondrion. Mutations in the protoporphyrinogen oxidase gene are responsible for variegate porphyria (21). Acute attacks of this disease can be effectively treated by intravenous administration of hematin. 

Hereditary coproporphyria HCP Coproporphyrinogen oxidase autosomal dominant... 

Guo R, Lim CK, Peters TJ. Accurate and specific HPLC assay of coproporphyrinogen oxidase activity in human peripheral lymphocytes. Clin Chun Acta 1988 177 245-52. 

Rhodanese (detected in both inner membrane and matrix) Coproporphyrinogen oxidase Protoporphyrinogen oxidase ... 

Mitochondrial coproporphyrinogen oxidase is localized in the intermembrane space and is probably loosely bound to the outer surface of the inner membrane. It catalyzes the successive conversion of propionic acid groups of ring A and ring B to vinyl groups (Figure 29-7). 

Coproporphyrinogen oxidase (CPO) Mitochondrial enzyme that catalyzes specifically the conversion of coproporphyrinogen III to protoporphyrinogen IX. 

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