Coproporphyrinogen III

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). 

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. 

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. 

Uroporphyrinogen decarboxylase 1 Coproporphyrinogen III Porphyria cutanea tarda (AD,1q34) J... 

Side chains don t quite alternate as you d deduced—you d deduced Next all acetates are decarboxylated— oxylated Coproporphyrinogen III is produced. 

Here we limit ourselves to an example of a 4Fe-4S center from the radical 5 -adenosyl-L-methioiiine (SAM) enzyme oxygen-independent coproporphyrinogen III oxidase HemN. This enzyme catalyzes the oxidative decarboxylation of coproporphyrinogen III to protoporphyrinogen IX dming bacterial heme biosynthesis. The crystal structure of Escherichia coli HemN revealed the presence of an unusually coordinated iron-sulfur cluster and two molecules of SAM. 

Mammalian heme biosynthesis traverses eight enzymatic steps and requires shuttling of the first intermediate, 5-aminolevulinic acid from the mitochondrion into the cytosol, and later transferring coproporphyrinogen III back into the mitochondrion for the three final biosynthetic steps (2). 

Hydroxymethylbilane Synthase (EC 2.5.1.61), HMBS HMBS (also known as porphobilinogen [PEG] deaminase) is a cytoplasmic enzyme that catalyzes the formation of one molecule of the linear tetrapyrrole 1-hydroxymethylbilane (HMB also known as preuroporphyrinogen) from four molecules of PEG with the release of four molecules of ammonia. The former enzyme committee designation for HMBS was EC 4.3.1.8, but in 2003 the enzyme was redesignated as EC 2.5.1.61. The enzyme has two molecules of its own substrate PEG, attached covalently to the apoenzyme as a prosthetic group. The enzyme is susceptible to allosteric inhibition by intermediates further down the heme biosynthetic pathway, notably coproporphyrinogen-III and protoporphyrinogen-IX. 

Formation of coproporphyrinogen III from uroporphyrinogen III. Acetic acid side chains (Ac) are decarboxylated to methyl groups (M), sequentially, starting clockwise from ring D. P, -CH2CH2COOH. 

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

Figure 12 Structure and enzymatic reaction of UROD. (a) Crystai structure of human UROD in compiex with the reaction product coproporphyrinogen iii. Each subunit of the dimeric protein consists of a /3a)s barrei. (b) During the UROD reaction the acetate side chains of uroporphyrinogen iii are decarboxyiated to yieid the corresponding methyi groups. The decarboxyiations proceed in an ordered manner beginning with ring D foiiowed by rings A, B, and finaiiy C.

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