Porphyrins, Chemistry Biosynthesis

Detailed reviews of porphyrin, chlorophyll and corrinoid biosynthesis have been written (e.g. B-79MI10404, B-76MI10403). The reader is referred in particular to the earlier account by Akhtar and Jordan in the companion series Comprehensive Organic Chemistry (B-79MI10406). 

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. 

Cancer, Topics in Chemical Biology Photosynthesis, Electron Transfer Chemistry in Porphyrin and Corrin Biosynthesis... 

Because of its immense scope, a detailed description of corrins (and vitamin B12) will not be presented here. The reader is instead referred to reviews of B12 chemistry and its biosynthesis that have appeared recently. Further, because they are more directly related to the corrins than are the corroles, the chemistry of the dehydrocorrins will not be discussed here. Also not included in this review are the so-called artificial porphyrins of Floriani, et al. (e.g., 2.5), since it is deemed by these authors in their review that these macrocycles are more dehydrocorrin-like than corrole-like in their nature. Other systems omitted here include the spiro porphyrins of Battersby and coworkers, the tetraphosphole macrocycles of Mathey and coworkers and the tetrapyrrolic systems of Bartczak and Smith and co-workers. Thus, the emphasis will be on those contracted porphyrins that are most removed, in structural and chemical terms, from the macrocyclic unit found in coenzyme B12 and its analogs. 

Akhtar, M., Jordan, P. M. Porphyrin, chlorophyll and corrin biosynthesis. In Comprehensive Organic Chemistry, Vol. 5, Biological Compounds, pp. 1121-1166. Pergamon Press, Oxford 1979... 

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

The biosynthesis and degradation of haem has been reviewed, " and also the pathobiochemistry of the porphyrias, whilst high-performance liquid chromatography (h.p.l.c.) has been used to differentiate between the various types of porphyria (abnormalities of porphyrin biosynthesis). Stereochemical aspects of metalloporphyrin chemistry have been discussed reviews on the organisation of chlorophyll in vivo and its role in photosynthesis have also appeared. Accounts of the structure and function of the vitamin B12 coenzyme and its mode of action, as well as its synthesis and biosynthesis, have been presented, and revised... 

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