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Abnormal haem biosynthesis in chronic alcoholics
Author(s) -
McCOLL KENNETH E. L.,
MOORE MICHAEL R.,
THOMPSON GEORGE G.,
GOLDBERG ABRAHAM
Publication year - 1981
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1981.tb02014.x
Subject(s) - ferrochelatase , uroporphyrinogen iii decarboxylase , endocrinology , medicine , dehydratase , porphyria , enzyme , heme , biochemistry , chemistry , biology
. The activities of six of the enzymes of haem biosynthesis have been examined in eleven chronic alcoholics admitted to hospital for alcohol withdrawal. The mitochondrial enzymes delta‐aminolae‐vulinic acid (ALA) synthase, coproporphyrinogen oxidase and ferrochelatase were monitored in peripheral leucocytes and the cytosolic enzymes ALA dehydratase, uroporphyrinogen‐1 ‐synthase and uro‐porphyrinogen decarboxylase in peripheral erythro‐cytes. Compared with control subjects 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) on the day after admission but all returned to normal by the tenth to twentieth days after alcohol withdrawal. This stimulation of ALA synthase and inhibition of uroporphyrinogen decarboxylase explains the mechanism by which chronic alcohol ingestion may precipitate cutaneous hepatic porphyria. Two of the alcoholics were anaemic without evidence of haematinic deficiency and this was associated with depressed ferrochelatase activity and iron and porphyrin accumulation. The anaemia and related biochemical abnormalities in these two subjects were all corrected with alcohol withdrawal. It is proposed that inhibition of ferrochelatase activity is the biochemical basis of alcohol related sideroblastic anaemia.