Coproporphyrin formation

For porphyrins of C4 symmetry, e.g. coproporphyrin I12 and etioporphyrin I,13 cyclotetrameriza-tion of a-(functionalized methyl)pyrrole is suitable, though the pyrrole synthesis is not always facile (Scheme 2). Drastic conditions or prolonged reaction occasionally cause isomeric by-product formation.2... 

Porphyrias are inherited or acquired disorders caused by a deficiency of enzymes in the heme biosynthetic pathway. Porphyrin is synthesized in both the erythroblasts and the liver, and either one may be the site of a disorder. Congenital erythropoietic pOTjdtyria, for example, prematurely destroys eythrocytes. This disease results from insufficient cosynthase. In this porphyria, the synthesis of the required amount of uroporphyrinogen III is accompanied by the formation of very large quantities of uroporphyrinogen I, the useless symmetric isomer. Uroporphyrin I, coproporphyrin I, and other symmetric derivatives also accumulate. The urine of... 

In Rhodopseudomonas spheroides [Lascelles and Hatch, 106] there is some evidence (Section Vlll) that heme represses ALA-synthetase formation. In mutants that could not make heme, more ALA-synthetase was found to accumulate than in wild type. On low iron, less heme was formed and more coproporphyrin accumulated, a result suggesting that, because heme was lacking, more ALA-synthetase was formed the latter action could be explained on the basis of either inhibition or repression of the enzyme by heme. 

Methionine deficiency leads to coproporphyrin accumulation. Lascelles and Hatch [145] suggested that heme formation may be inhibited under these conditions, perhaps at the iron insertion step because methionine is required for the synthesis of phosphatidyl choline and the latter appears to be needed for ferrochelatase activity. Tait [147a] reported that under anaerobic conditions the conversion of coproporphyrinogen to protoporphyrinogen required methionine, ATP, and ferrous ions. 

Lead interferes with the normal formation of haemoglobin, causing anaemia, but the diagnosis of excessive absorption should be made before anaemia appears. The same interfering mechanism causes abnormal products to appear in the urine, e.g. amino laevulinic acid (ALA) and coproporphyrin. These products are useful indicators of excessive lead absorption or poisoning. 

Accumulation of urinary coproporphyrin has also been reported, principally in highly exposed children and lead workers and mainly in the older literature (Chisolm and Harrison, 1956 Haeger-Aronsen, 1960). CP accumulation, from inhibition by lead of coproporphyrin utilization in subsequent formation of protoporphyrin, is a relatively late responder to Pb exposure in both children and workers, and the association of urinary CP with PbB principally is seen at PbB values 40 pg/dl. It has rarely been used in recent... 

The decarboxylation of uroporphyrin to coproporphyrin is also compatible with chemical knowledge, since the heating of uroporphyrin results in the formation of coproporphyrin. ... 

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