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The effects of acute ethanol ingestion on the activities of the enzymes of haem biosynthesis in peripheral blood cells have been monitored in eight healthy subjects. The mitochondrial enzymes delta-aminolaevulinic acid (ALA) synthase, coproporphyrinogen oxidase and ferrochelatase were measured in leucocytes and the cytosolic enzymes ALA dehydratase, porphobilinogen (PBG) deaminase and uroporphyrinogen decarboxylase in erythrocytes. Ingestion of 1 . 316 mol ethanol resulted in increased activity of the rate-controlling enzymes ALA synthase and PBG deaminase and decreased activity of the other four enzymes. There was also increased urinary excretion of coproporphyrin. These observations may be relevant to the biochemical mechanisms involved in the ethanol-related conditions, sideroblastic anaemia, cutaneous hepatic porphyria and hepatic siderosis.

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-aminolaevulinic acid (ALA) synthase, coproporphyrinogen oxidase and ferrochelatase were monitored in peripheral leucocytes and the cytosolic enzymes ALA dehydratase, uroporphyrinogen-1-synthase and uroporphyrinogen decarboxylase in peripheral erythrocytes. Compared with control subjects the activity of the initial and rate controlling enzyme of the pathway, ALA synthase, was increased (P less than 0.01) and the activities of ALA dehydratase and uroporphyrinogen decarboxylase depressed (P less than 0.01, P less than 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.

Protoporphyrinogen oxidase activity and ferrochelatase activity were measured in leucocytes from patients with porphyria variegata. The mean activity of protoporphyrinogen oxidase (PPO) in porphyria variegata (PV) was about 50% of normal (P less than 0.05). The mean activity of ferrochelatase with 59Fe2+ sulphate and protoporphyrin as substrates (in the presence of ascorbic acid) was reduced by 40% (P less than 0.009). The mean activity of ferrochelatase with 59Fe3+ chloride and protoporphyrin as substrates (in the presence of reduced glutathione) was increased by 65% (P less than 0.005). Both are statistically highly significant. The findings are interpreted as follows: (a) The occurrence of a low level of protoporphyrinogen oxidase in PV is confirmed. (b) The findings indicate a concurrent structural change in ferrochelatase (this may be structurally related to (a) but no evidence of this is at present available).