Ethanol consumption decreases alanine uptake by rat basolateral liver plasma membrane vesicles

Abstract

Alterations of amino acid metabolism may play an important role in the pathogenesis of ethanol-induced liver disease. Previous studies indicate that ethanol added in vitro inhibits amino acid uptake by cultured hepatocytes and liver plasma membrane vesicles; however, the effect of chronic ethanol consumption on amino acid uptake by the liver remains unknown. Therefore, the present studies were performed to determine if chronic ethanol consumption impairs alanine uptake by rat basolateral liver plasma membrane vesicles. Male Sprague-Dawley rats were pair-fed for 6 weeks a diet containing 36% of calories as ethanol or a control diet in which ethanol was isocalorically replaced with carbohydrate. Chronic ethanol consumption reduced basolateral liver plasma membrane sodium-dependent alanine transport activity by 36.3% ± 15.9% (p < 0.01). This reduction was caused primarily by impaired activity of amino acid transport system A. The response of system A to glucagon was reduced in the ethanol-fed rats, suggesting that impaired hormonal regulation is at least partially responsible for the lower system-A activity. Kinetic analysis shows that ethanol consumption reduces the Vmax of sodium-dependent alanine transport without affecting the Km. These studies indicate that chronic ethanol consumption reduces alanine uptake by the rat liver. They further show that the reduced uptake is at least partially caused by an intrinsic defect in membrane-transport processes rather than another regulatory mechanism.