A B S T R A C T Individuals with chronic alcohol abuse frequently exhibit lowered plasma levels of pyridoxal 5'-phosphate, the coenzyme form of vitamin Be. Because the liver is the primary source of this coenzyme in plasma and also the principal organ that oxidizes ethanol, the effect of ethanol on hepatic pyridoxal phosphate metabolism was studied in the rat. The chronic feeding of ethanol (36% of the total dietary calories) for 6 wk significantly decreased the hepatic pyridoxal phosphate content both in animals given a sufficient amount of vitamin Be in their diet and in those rendered vitamin Be deficient. In isolated perfused livers, the addition of 18 mM ethanol lowered the pyridoxal phosphate content of livers from vitamin B.-sufficient animals and decreased the net synthesis of pyridoxal phosphate from pyridoxine by the livers of vitamin Be-deficient animals. Ethanol also diminished the rate of release of pyridoxal phosphate into the perfusate by the livers of vitamin Be-deficient rats. These effects of ethanol, in vitro, were abolished by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase. Thus the derangement of pyridoxal phosphate metabolism produced by ethanol is dependent upon its oxidation. These data support previous findings which indicate that acetaldehyde is the responsible agent which acts by accelerating the degradation of intracellular pyridoxal phosphate.This work was presented at the Annual Meeting of the Central Society for Clinical Research, Chicago, Ill. (1974 Since the liver is the principal organ responsible for the oxidation of ethanol, the nature of the derangement in PLP metabolism can be most directly elucidated by studies with hepatic tissue. The liver also plays a central role in the metabolism of vitamin Be: a major portion of the pyridoxine absorbed by the intestine is accumulated by liver (3) and PLP in plasma is derived principally from the liver (4). In this communication, we report both the effect of chronic ethanol administration upon the hepatic PLP content of rats and the acute effect of ethanol oxidation upon PLP metabolism in isolated perfused rat livers.Isolated perfused livers have not been previously employed to study PLP metabolism. In the course of 'Abbreviation used in this paper: PLP, pyridoxal 5'-phos- METHODSExperimental animals. All animals were male SpragueDawley rats (Laboratory Supply Co., Indianapolis, Ind.), housed in wire-bottomed cages and in a controlled temperature environment with fixed day-night cycles. To study the chronic effect of ethanol on hepatic PLP content in vivo, rats were pair-fed the liquid diets as described by Lieber and DeCarli (5). The alcohol diet contained 18% of the calories as protein, 35% as fat, 11% as carbohydrate, and 36% as ethanol. The control diet was identical except that ethanol was isocalorically replaced with dextrin-maltose. Both diets contained 0.725 ,ug pyridoxine-HCl/ml. Rats weighing 150-170 g were pair-fed these diets for 52+3 days and were considered to be vitamin B. sufficient. Another group of rats was ...

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