description
General Background Heme (protoheme, heme b) is an iron-containing porphyrin, that belongs to the family of macrocyclic tetrapyrroles. It has a diverse range of biological functions as a prosthetic group in many enzymes, transporters, and receptors. Heme containing cytochromes are integral components of the respiratory chain that mediate electron transfer. Heme containing proteins such as hemoglobin are involved in diatomic gas transport. As a prosthetic group in several enzymes, heme is also involved in enzyme catalysis . Heme is biosynthesized as : PROTOHEME, and different derivatives of protoheme can be formed that differ in modifications to the porphyrin ring, including how it is bound to the protein. About this Pathway Heme biosynthesis is a vital process for most living organisms and the pathway has been highly conserved through evolution . In eukaryotes, heme is produced in eight steps by eight enzymes divided between the mitochondria and cytoplasm, beginning with the condensation of : GLY and : SUC-COA to yield : 5-AMINO-LEVULINATE in the mitochondria . : SUC-COA "Succinyl CoA" is derived from the TCA cycle. The rate limiting preliminary reaction is catalyzed by : CPLX66-342/: CPLX66-341. : 5-AMINO-LEVULINATE is the sole source of carbon and nitrogen atoms that eventually get incorporated into heme. Two : 5-AMINO-LEVULINATE condense to form the pyrrole : PORPHOBILINOGEN . Four : PORPHOBILINOGEN oligomerize to yield the first linear tetrapyrrole intermediate : HYDROXYMETHYLBILANE . Ring closure gives rise to the first tetrapyrrole : UROPORPHYRINOGEN-III . The intermediate reactions of the pathway occur in the cytosol, with the initial and terminal three steps of heme biosynthesis occurring within the mitochondria. The enzymes for the mitochondrial reactions are located in the inner mitochondrial membrane . Two of the last three steps in the pathway require the presence of molecular oxygen. The heme biosynthetic pathway occurs in all cells types as heme is required as a cofactor for the respiratory cytochromes and for the terminal stages of red cell differentiation in erythropoiesis. In humans, defects in any of the enzymes of the pathway lead to a group of inherited disorders called porphyrias

external resources
NCBI:545289
BIOCYC:HUMAN_PWY-5920
PUBMED:6769048
PUBMED:7592564
PUBMED:3816774
PUBMED:20506125
PUBMED:23471474
PUBMED:9564029
PUBMED:7592562
PUBMED:3346226

genes
ALAD , ALAS1 , ALAS2 , CPOX , FECH , HMBS , PPOX , UROS ,