Abnormal haem biosynthesis in chronic alcoholics

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Abstract
The activities of 6 enzymes of heme biosynthesis were examined in 11 chronic alcoholics admitted to a hospital for alcohol withdrawal. The mitochondrial enzymes .delta. aminolevulinic acid (ALA) synthase, coproporphyrinogen oxidase and ferrochelatase were monitored in peripheral leukocytes and the cytosolic enzymes ALA dehydratase, uroporphyrinogen-1-synthase and uroporphyrinogen decarboxylase in peripheral erythrocytes. Compared with controls the activity of the initial and rate controlling enzyme of the pathway, ALA synthase, was increased (P < 0.01) and the activities of ALA dehydratase and uroporphyrinogen decarboxylase depressed (P < 0.01, P < 0.02, respectively) 1 day after admission but all returned to normal by the 10th-20th days after alcohol withdrawal. This stimulation of ALA synthase and inhibition of uroporphyrinogen decarboxylase explained the mechnism by which chronic alcohol ingestion may precipitate cutaneous hepatic porphyria. Two alcoholics were anemic without evidence of hematinic deficiency and this was associated with depressed ferrochelatase activity and Fe and porphyrin accumulation. The anemia and related biochemical abnormalities in these 2 subjects were corrected with alcohol withdrawal. Inhibition of ferrochelatase activity was the biochemical basis of alcohol related sideroblastic anemia.