Porphyrin Metabolism Heme biosynthesis

Within the past few years, there has been considerable progress in understanding the role played by the mitochondria in the cellular homeostasis of iron. Thus, erythroid cells devoid of mitochondria do not accumulate iron (7, 8), and inhibitors of the mitochondrial respiratory chain completely inhibit iron uptake (8) and heme biosynthesis (9) by reticulocytes. Furthermore, the enzyme ferrochelatase (protoheme ferro-lyase, EC 4.99.1.1) which catalyzes the insertion of Fe(II) into porphyrins, appears to be mainly a mitochondrial enzyme (10,11,12,13, 14) confined to the inner membrane (15, 16, 17). Finally, the importance of mitochondria in the intracellular metabolism of iron is also evident from the fact that in disorders with deranged heme biosynthesis, the mitochondria are heavily loaded with iron (see Mitochondrial Iron Pool, below). It would therefore be expected that mitochondria, of all mammalian cells, should be able to accumulate iron from the cytosol. From the permeability characteristics of the mitochondrial inner membrane (18) a specialized transport system analogous to that of the other multivalent cations (for review, see Ref. 19) may be expected. The relatively slow development of this field of study, however, mainly reflects the difficulties in studying the chemistry of iron. 

The next step in heme biosynthesis, is the condensation of two molecules of ALA, via the enzyme ALA dehydratase, to give the pyrrole called porphobilinogen or PBG. This compound was first identified in the urine of patients suffering from one of a family of diseases of porphyrin metabolism, called porphyrias. Labelled PBG has been efficiently incorporated into heme using chicken blood as the biosynthetic model system. What is interesting about the biosynthesis of PBG is that it is very similar... 

Porphyrin Metabolism and Porphyria 201 Chemistry of Porphyrins Biosynthesis of Porphyrins Heme Synthesis... 

A major metabolic fate of glycine is the biosynthesis of tetrapyrroles, compounds which contain four linked pyrrole rings. Four classes of these compounds include 1) Heme (an iron porphyrin) 2) Chlorophylls 3) Phycobilins (photosynthetic pigments of algae and 4) Cobalamins (Vitamin B12 and derivatives). 

---