Mechanisms
Alcohol abuse alters CETP glycosylation, lowering its surface charge and likely its activity (Alcohol Alcohol 2006)
Original title: Defective glycosylation of cholesteryl ester transfer protein in plasma from alcohol abusers
Because alcohol consumption reduces the carbohydrate content of some glycoproteins and CETP activity is known to be low in alcohol abusers, researchers compared CETP structure in 10 alcohol abusers and 10 controls after partially purifying plasma CETP by FPLC. CETP had a slightly lower molecular weight in alcohol abusers than controls (50.6-84.0 kDa versus 51.3-85.0 kDa) and a higher isoelectric point, indicating reduced negative surface charge; treating control CETP with neuraminidase, which strips sialic acid from glycoproteins, produced a similar shift. The authors conclude CETP from alcohol abusers likely has a glycosylation defect from impaired sialylation caused by alcohol or its metabolite acetaldehyde, and that this altered glycosylation and lipoprotein binding may explain the low CETP activity previously observed in alcoholic subjects.
Original abstract
Aims: Alcohol consumption reduces the carbohydrate content of some glycoproteins, e.g. carbohydrate-deficient transferrin. The aim of this study was to investigate if there is such an alcohol-induced glycosylation defect in plasma cholesteryl ester transfer protein (CETP). A defect in the posttranslational glycosylation of CETP may affect its structure and electrical charge and may therefore affect its function. CETP activity is low in alcohol abusers.
Methods: We studied the effect of alcohol consumption on CETP properties in 10 alcohol abusers and 10 control subjects. CETP was partially purified from lipoprotein-free plasma by FPLC using a Phenyl-Sepharose column. Isoelectric focusing, polyacrylamide gel electrophoresis, and western blotting were performed for partially purified CETP.
Results: CETP had a lower molecular weight in the alcohol abusers than in the controls (range 50.6-84.0 kDa in the alcohol abusers vs 51.3-85.0 kDa in the controls). CETP purified from alcohol abusers had a higher isoelectric point, indicating a lower negative charge on the surface of the protein than in the controls' CETP. A similar effect was observed when control CETP was incubated with neuraminidase, an enzyme which is known to remove sialic acid from glycoproteins.
Conclusions: We conclude that CETP from alcohol abusers may have a glycosylation defect due to defective sialylation caused posttranslationally by alcohol itself or its metabolite acetaldehyde. The defective glycosylation of CETP associated with altered binding to lipoproteins may lead to the low CETP activity observed previously in alcoholic subjects.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.