Biosynthesis of porphyrin

The recent review on vitamin Bi2 in this series (G18) provides an excellent survey. In current research emphasis is placed on the biosynthesis and the coenzyme forms of vitamin Bi2 (R2). Similarity between biosynthesis of porphyrin and vitamin Bi2 was shown by the incorporation of 6 -aminolevulic acid into the vitamin by a microorganism (S4). The l-amino-2-propanol moiety of vitamin Bj2 may be formed by decarboxylation of threonine (K10). Nothing is yet known about the nature of the precursors of the dimethylbenzimidazole portion of vitamin Bi2. 

Orotic acid added to rat diet also provokes an. excessive biosynthesis of porphyrins in liver, erythrocytes and bone marrow. Administration of adenine monophosphate (AMP) counteracted this effect of orotic acid intoxication [165]. Haemorrhagic renal necrosis in rats, caused by choline deficiency, can be relieved by orotic acid [166], Simultaneous supplementation of the diet with adenine does not influence the protective effect of orotic acid. It has been suggested that orotic acid may lower the body requirement for choline through a metabolic interaction—orotic acid may stimulate the cytidine phosphate choline pathway of lecthin biosynthesis [166]. 

Under acidic conditions, porphobilinogen undergoes self-condensation to give a mixture of four isomeric cyclic tetrapyrroles, uroporphyrinogens I (68), II (69), III (70) and IV (71) in the ratio 1 1 4 2. Uroporphyrinogens II and IV are not known to occur naturally and uroporphyrinogen I has only been detected in vivo under exceptional conditions. Uroporphyrinogen III is the only isomer which acts as an intermediate in the biosynthesis of porphyrins and corrinoids. 

Figure 24-21 Biosynthesis of porphyrins, chlorins, and related compounds.

Primary amine catalysis (usually involving a lysine residue) has been recognised to play an important role in various enzyme-catalysed reactions. Examples are the conversion of acetoacetate to acetone catalysed by acetoacetate decarboxylase, the condensation of two molecules of S-aminolevulinic acid catalysed by -aminolevulinic deshydratase during the biosynthesis of porphyrins, and the reversible aldol condensation of dihydroxy-acetone phosphate with glyceraldehyde which in the presence of aldolase yields fructose-1-phosphate (64) (For reviews see, for example, Snell and Di Mari,... 

The catabolism of haemoglobin yields haem, which is subsequently converted to bilirubin in a two-step process that takes place in the hepatocyte. First, the microsomal enzyme haem oxygenase cleaves the porphyrin ring of haem, generating biliverdin in an energy-utilising reaction. Following this, biliverdin is converted to bilirubin by the cytosolic enzyme biliverdin reductase. As the liver is the active site for biosynthesis of porphyrin and haem, deficiencies in some enzymes of the porphyrin pathway may lead to insufficient haem production and an increase in porphyrin levels, which causes acute porphyria attacks. 

D. Shemin. 1989. An illustration of the use of isotopes The biosynthesis of porphyrins Bioessays 10 30-35. (PubMed) Books... 

Figure 1. Biosynthesis of porphyrins by purple nonsulfur bacteria.

Jackson AH, Sancovich HA, Ferramola AM, Evans N, Games DE, Matlin SA, et al. Macrocyclic intermediates in the biosynthesis of porphyrins. Phil Trans Roy Soc 1976 273 191-206. 

Battersby AR, McDonald E (1975) Biosynthesis of porphyrins, chlorins and corrins. In Smith KM (ed) Porphyrins and metalloporphyrins. Elsevier, Amsterdam, p 61... 

This highly distinctive labeling pattern led Shemin to propose that a heme Pi ecursor is formed by the condensation of glycine with an activated succinyl compound. In fact, the first step in the biosynthesis of porphyrins in mammah 15 the condensation of glycine and. succinyl CoA to form 8-aminolevulinate. 

The first steps in the biosynthesis of porphyrins from porphobilinogen (PBG)... 

The biosynthesis of porphyrin involves the formation of porphobilinogen from two molecules of S-aminolevulinic acid. The precise mechanism for this biosynthesis is as yet unknown. A possible mechanism starts with the formation of an imine between the enzyme that catalyzes the reaction and one of the molecules of S-aminolevulinic acid. An aldol-type condensation occurs between the imine and a free molecule of d-aminolevulinic acid. Nucleophilic attack by the amino group on the imine closes the ring. The enzyme is then eliminated, and removal of a proton creates the aromatic ring. 

E. Ivanov, M. Pisanets (1982). Studies on the biosynthesis of porphyrins in erythrocytes after incubation with -aminolevulinic acid An attempt to investigate the pathogenesis of nephrogenic anemia. Acta Biol. Med. Germ., 41, 307-313. 

These results agree, in the literature review performed, with the studies published by numerous authors and refered in the Doctoral Thesis of Gonzalez-Lopez (1992) and others (Sakai, 2000 Gurer-Orhan et al., 2004). All of them showed the influence of Pb on the heme biosynthesis pathway and the effects produced in some of the enzymes which take part in the biosynthesis of porphyrins, phenomena demonstrated in clinical research, in vitro studies and in experiments on animals. 

R is the 5,22-dihydro- porphyrin skeleton isomeric to chlorin in which the conjugation is interrupted it plays a role in the biosynthesis of porphyrin and the total synthesis of chlorophyll. Close relatives of P. are the porphomethenes in which the conjugation is also interrupted and which represent to the bacteriochlo-rins and isobacteriochlorins isomeric tetrahydropor-... 

An example of a carbohydrate auxiliary being used for chromatographic enantioseparation is the derivatization of 434 with 3,4-0-benzylidene-D-ribonic acid 5-lactone. These diastereomeric products could then be separated by HPLC. The enantiopure 434 (containing a chiral quaternary centre) was used to prepare 435, believed to be involved in the biosynthesis of porphyrins. ... 

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