Alcohol and porphyrin metabolism.
Alcohol is a porphyrinogenic agent which may cause disturbances in porphyrin metabolism in healthy persons as well as biochemical and clinical manifestations of acute and chronic hepatic porphyrias. After excessive consumption of alcohol, a temporary, clinically asymptomatic secondary hepatic coproporphyrinuria is observable, which can become persistent in cases of alcohol-induced liver damage. Nowadays, the alcohol-liver-porphyrinuria syndrome is the first to be mentioned in secondary hepatic disturbances of porphyrin metabolism. Acute hepatic porphyrias (acute intermittent porphyria, variegate porphyria and hereditary coproporphyria) are considered to be molecular regulatory diseases, in contrast to non-acute, chronic hepatic porphyria, clinically appearing as porphyria cutanea tarda (PCT). Porphyrins do not accumulate in the liver in acute porphyrias, whereas in chronic hepatic porphyrias they do. Thus, chronic hepatic porphyria is a porphyrin-accumulation disease, whereas acute hepatic porphyrias are haem-pathway-dysregulation diseases, characterized in general by induction of delta-aminolevulinic acid synthase in the liver and excessive stimulation of the pathway without storage of porphyrins in the liver. The clinical expression of acute hepatic porphyrias can be triggered by alcohol, because alcohol augments the inducibility of delta-aminolevulinic acid synthase. In chronic hepatic porphyrias, however, which are already associated with liver damage, alcohol potentiates the disturbance of the decarboxylation of uro- and heptacarboxyporphyrinogen, which is followed by a hepatic accumulation of uro- and heptacarboxyporphyrin and their sometimes extreme urinary excretion. Especially in persons with a genetic deficiency of uroporphyrinogen decarboxylase, but also in patients with the so-called sporadic variety of PCT, alcohol is able to transform an asymptomatic coproporphyrinuria into PCT. Alcohol has many biochemical and clinical effects on porphyrin and haem synthesis both in humans and laboratory animals. Ethanol suppresses the activity of porphobilinogen synthase (synonym: delta-aminolevulinic acid dehydratase), uroporphyrinogen decarboxylase, coproporphyrinogen oxidase and ferrochelatase, whereas it induces the first and rate-limiting enzyme in the pathway, delta-aminolevulinic acid synthase and also porphobilinogen deaminase. Therefore, teetotalism is a therapeutically and prophylactically important measure in all types of hepatic porphyrias.
Doss
M O
MO
Division of Clinical Biochemistry, Faculty of Medicine of the Philipps University, D-35037 Marburg, Germany.
Kühnel
A
A
Gross
U
U
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D003304:Coproporphyrinogen Oxidase / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D018450:Disease Progression; D000431:Ethanol / Q000009:adverse effects*; D005294:Ferrochelatase / Q000378:metabolism; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000378:metabolism; D000623:Porphobilinogen Synthase / Q000378:metabolism; D011164:Porphyrias / Q000145:classification / Q000175:diagnosis / Q000235:genetics; D011166:Porphyrins / Q000378:metabolism*
D018076:DNA, Complementary; D011166:Porphyrins; D000431:Ethanol; D003304:Coproporphyrinogen Oxidase; D011163:Hydroxymethylbilane Synthase; D000623:Porphobilinogen Synthase; D005294:Ferrochelatase