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.