Biosynthesis of porphobilinogen. ALA synthase occurs in the mitochondria,whereas ALA dehydratase is present in the cytosol.The substrates are succinyl-CoA and glycineThe product is delta-aminolevulinic acid (ALA).An essential cofactor is pyridoxal phosphate (vit B-6).This is the rate-limiting reaction of heme synthesis in alltissues, and it is therefore tightly regulated.
The substrates are two molecules of ALA.The product is porphobilinogen, the first pyrrole.ALA dehydratase is a -SH containing enzyme.• It is very susceptible to inhibition by lead.
Conversion of porphobilinogen to uroporphyrinogens.Uroporphyrinogen synthase I is alsocalled porphobilinogen (PBG) deaminase or hydroxymethylbilane(HMB) synthase.
Decarboxylates the acetic acid groups, converting them tomethyl groups.
Catalyzes the conversion of two propionic acid groups to vinylGroupsProtoporphyrinogen IX oxidase converts the methylenebridges between the pyrrole rings to methenyl bridges.Ferrochelatase adds Fe++ to protoporphyrin IX, formingheme.• The enzyme requires Fe++, ascorbic acid and cysteine(reducing agents).• Ferrochelatase is inhibited by lead.
•Reactions of Heme synthesis
Formation of Porphobillinogen
Formation of Hydroxymrthylbilane
Formation of Uroporphyrinogen
Synthesis of Coproporphyrinogen
Synthesis of Protoporphyrinogen
Generation of Protoporphyrin
Generation of Heme