Serum carbohydrate-deficient transferrin: Mechanism of increase after chronic alcohol intake

Abstract

Carbohydrate-deficient transferrin (CDT) is now considered to be the most sensitive and specific biological marker of alcohol abuse. However, the mechanism by which chronic alcohol consumption causes an elevation of CDT levels in serum is still not understood. Therefore, we fed eight pairs of male rats a nutritionally adequate liquid diet containing either alcohol (36% of energy) or isocaloric dextrose (control) for 4 weeks, after which blood and liver samples were obtained. Serum CDT content in alcohol-treated rats increased by 45% ( P < .05) as assessed with an isoelectric focusing/Western blot method (IEF/WB) thereby mimicking the clinical condition. In particulate fractions (plasma membranes) prepared from the liver samples, the activity of sialidase was increased 1.62-fold ( P < .05) in ethanol-fed animals compared with their corresponding controls. In contrast, in rats fed ethanol, the activities of sialyltransferase (ST), galactosyltransferase (GT), and N-acetylglucosamine transferase ( N-AGT), which are glycosyltransferases involved in transferrin carbohydrate side chain synthesis, were diminished by 24% and 40% ( P < .05), 23% and 51% ( P < .05, .001), and 20% and 26% ( P < .05) in total liver homogenates and Golgi fraction (GF) 1, respectively, when expressed as units/100 g body weight. These enzymes were also significantly less active in hepatic GFs 2 and 3. The depression of the transferase activities in ethanol-fed rats appeared to be due, at least in part, to enzyme inactivation by acetaldehyde, whereas ethanol itself was without effect. Similar results were obtained in humans: five alcohol abusers were found to exhibit a 23% decrease in hepatic sialyltransferase and a 41% increase in sialidase activities, respectively, when compared with three nondrinking subjects. In conclusion, the increased activity of sialidase in liver particulate fractions, combined with the decrease in transferrin glycosyltransferases in GFs, mediated by ethanol (or acetaldehyde derived from ethanol) most likely accounts for the enhanced serum CDT in response to chronic ethanol consumption in rats as well as in humans.