Doss M O, Kühnel A, Gross U
Division of Clinical Biochemistry, Faculty of Medicine of the Philipps University, D-35037 Marburg, Germany.
Alcohol Alcohol. 2000 Mar-Apr;35(2):109-25. doi: 10.1093/alcalc/35.2.109.
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.
酒精是一种可致卟啉生成的物质，可在健康人身上引起卟啉代谢紊乱，以及急性和慢性肝卟啉病的生化和临床表现。过量饮酒后，可观察到一种暂时的、临床上无症状的继发性肝粪卟啉尿症，在酒精性肝损伤的情况下可能会持续存在。如今，酒精-肝-卟啉尿症综合征是继发性肝卟啉代谢紊乱中首先被提及的病症。与非急性、慢性肝卟啉病（临床上表现为迟发性皮肤卟啉病，PCT）不同，急性肝卟啉病（急性间歇性卟啉病、混合型卟啉病和遗传性粪卟啉病）被认为是分子调节疾病。在急性卟啉病中，卟啉不会在肝脏中蓄积，而在慢性肝卟啉病中则会蓄积。因此，慢性肝卟啉病是一种卟啉蓄积性疾病，而急性肝卟啉病是血红素途径调节异常疾病，其一般特征是肝脏中δ-氨基-γ-酮戊酸合酶的诱导以及该途径的过度刺激，且卟啉不在肝脏中储存。急性肝卟啉病的临床症状可由酒精引发，因为酒精会增强δ-氨基-γ-酮戊酸合酶的诱导作用。然而，在已经伴有肝损伤的慢性肝卟啉病中，酒精会增强尿卟啉原和七羧基卟啉原脱羧作用的紊乱，随后尿卟啉和七羧基卟啉在肝脏中蓄积，并有时会出现极高的尿排泄量。特别是在尿卟啉原脱羧酶基因缺陷的人群中，以及在所谓散发性PCT患者中，酒精能够将无症状的粪卟啉尿症转变为PCT。酒精对人和实验动物的卟啉和血红素合成具有多种生化和临床作用。乙醇会抑制胆色素原合酶（同义词：δ-氨基-γ-酮戊酸脱水酶）、尿卟啉原脱羧酶、粪卟啉原氧化酶和亚铁螯合酶的活性，而它会诱导该途径中的第一种且是限速酶，即δ-氨基-γ-酮戊酸合酶以及胆色素原脱氨酶。因此，在所有类型的肝卟啉病中，戒酒都是一项在治疗和预防方面都很重要的措施。
