Coproporphyrinogen

Figure 32-7. Decarboxylation of uroporphyrinogens to coproporphyrinogens in cytosol. (A, acetyl M, methyl P, propionyl.)... 

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. 

Although oxygen was found to be the only oxidant for conversion of coproporphyrinogen III to protoporphyrin IX, anaerobic systems must obviously exist for the biosynthesis of the latter molecule (43). Porphine itself has not been found in nature but spectral lines identical to those of bis-pyridylmagnesiumtetrabcnzoporphine have been detected in interstellar space (53). 

Interferes with chlorophyll formation in plants by inhibiting the conversion of coproporphyrinogen to proporphyrinogen by competing with iron... 

Initially, the four acetate residues (Ri) are decarboxylated into methyl groups. The resulting coproporphyrInogen III returns to the mitochondria again. The subsequent steps are catalyzed by enzymes located either on or inside the inner mitochondrial membrane. 

This enzyme [EC 1.3.3.3] (also referred to as copropor-phyrinogenase, coproporphyrinogen-III oxidase, and coprogen oxidase) catalyzes the reaction of coproporphyrinogen-111 with dioxygen to generate protoporphy-rinogen-lX and two carbon dioxide molecules. Iron ions are required as cofactors. 

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... 

The first porphyrin intermediate of the biosynthetic pathway is uroporphyrinogen, which is stepwise decarboxylated by uroporphyrinogen decarboxylase to heptacarboxy-, hexacarboxy-, pentacarboxy-, and coproporphyrinogen. This latter compound proceeds, as indicated in Fig. 7.3.1, to protoporphyrinogen and protoporphyrin. The oxidized uroporphyrin and its decarboxylation products up to coproporphyrin are assayed in urine. Coproporphyrin and the further downstream intermediaries can be recovered from feces as described below. 

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... 

Figure 7.13 The heme biosynthesis pathway. ALA, 5-aminolevulinic acid PBG, porphobilinogen uro gen, uroporphyrinogen copro gen, coproporphyrinogen prot gen, protoporphyrinogen Ac, acetate Pr, propionate vi, vinyl. (Reproduced by permission from Preface. Enzyme 28 91-93, 1982.)...

Uroporphyrin I and coproporphyrin I will be present in the urine. In the absence of uroporphyrinogen cosynthase, hydroxymethyl bilane will spontaneously cyclyze into uroporphyrinogen I. Some of it will be oxidized to uroporphyrin I. Some will be decarboxylated by uroporphyrinogen decarboxylase to coproporphyrinogen I and then oxidized to coproporphyrin I. None of these will be degraded by heme oxidase. 

If coproporphyrinogen III decarboxylase (oxidase) was not functioning normally, there would be a shortage of protoporphyrinogen IX. Hence its oxidation product, protoporphyrin IX, would not be excreted. The four other compounds would be found in abnormal amounts in blood or feces. 

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