Mechanisms of thiamin deficiency in chronic alcoholism.
In the United States and other developed countries thiamin deficiency is often related to chronic alcoholism. A number of mechanisms may be involved in the pathogenesis of thiamin deficiency in the alcoholic population. An important cause is inadequate intake of thiamin. Moreover, there may be decreased converstion of thiamin to the active coenzyme, reduced hepatic storage of the vitamin in patients with fatty metamorphosis, ethanol inhibition of intestinal thiamin transport, and impaired thiamin absorption secondary to other states of nutritional deficiency. The present discussion focuses on the mechanism of ethanol-related thiamin malabsorption. Under normal conditions thiamin transport in animals and humans is biphasic. At low or physiological thiamin concentrations, transport is a saturable, carrier-mediated, active process; but at higher concentrations, the transport of thiamin is predominantly passive. Ethanol reduces the rate of intestinal absorption and the net transmural flux of thiamin. Furthermore, ethanol inhibits only the active and not the passive component of thiamin transport by impeding the cellular exit of thiamin across the basolateral or serosal membrane. The impairment of thiamin movement out of the enterocyte correlates with a fall in the activity of Na-K ATPase. Bound to the basolateral membrane, Na-K ATPase is believed to be involved in the kinetics of active transport. Ethanol also increases the fluidity of enterocyte brush border and basolateral membranes. Since ethanol increases membrane fluidity it is possible that tahe impairment of thiamin transport and the diminution of Na-K ATPase activity may be related, at least partly, to a physical perturbation of the enterocyte membrane.
D000437:Alcoholism / Q000150:complications* / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D007421:Intestine, Small / Q000503:physiopathology; D008099:Liver / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects; D008954:Models, Biological; D009748:Nutrition Disorders / Q000150:complications; D012704:Serous Membrane / Q000503:physiopathology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013831:Thiamine / Q000378:metabolism; D013832:Thiamine Deficiency / Q000209:etiology*; D013835:Thiamine Pyrophosphate / Q000096:biosynthesis
D000431:Ethanol; D000254:Sodium-Potassium-Exchanging ATPase; D013835:Thiamine Pyrophosphate; D013831:Thiamine