Glycoprotein glycosyltransferase activities in serum in alcohol-abusing patients and healthy controls.
The activities of glycoprotein sialyl-, galactosyl- and N-acetylglucosaminyl-transferase in serum were examined in 14 alcoholic patients with a median BAC of 65 mmol/l and in 14 healthy age- and sex-matched controls. The median alcohol intake of the patients was 250 g/day for 1-3 weeks. All had elevated levels of carbohydrate-deficient transferrin in serum and normal or near normal liver function tests. The activities of galactosyl- and N-acetylglucosaminyl-transferase at subsaturated substrate concentration were significantly reduced in the patients. Vmax for all three enzymes was 35-55% lower in the patients than in the controls. Ethanol up to 500 mmol/l had no effect on these enzymes in serum. Acetaldehyde up to 200 mumol/l produced a significant dose-dependent inhibition of all three glycosyltransferases ranging from 19 to 44% at 200 mumol/l. Pyridoxal-5'-phosphate had a similar inhibitory effect on all enzyme activities suggesting the presence of lysine in the substrate or acceptor sites, or in the glycoprotein acceptors. The latter finding provides a possible molecular basis for acetaldehyde to modify glycosyl transfer. The results indicate that in man, alcohol abuse is connected with reduced activities of several glycosyltransferases in serum, which may reflect an important mechanism behind the carbohydrate deficiencies in secretory as well as membrane-bound glyconjugates in alcoholic patients.
Stibler
H
H
Department of Neurology, Karolinska Hospital, Stockholm, Sweden.
Borg
S
S
D000079:Acetaldehyde / Q000494:pharmacology; D000328:Adult; D000437:Alcoholism / Q000201:enzymology*; D005700:Galactosyltransferases / Q000097:blood; D005964:Glucosyltransferases / Q000097:blood; D006602:Hexosyltransferases / Q000037:antagonists & inhibitors / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases; D011732:Pyridoxal Phosphate / Q000494:pharmacology; D012799:Sialyltransferases / Q000097:blood; D014168:Transferrin / Q000031:analogs & derivatives / Q000378:metabolism; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D014168:Transferrin; C056759:carbohydrate-deficient transferrin; D011732:Pyridoxal Phosphate; D005700:Galactosyltransferases; D005964:Glucosyltransferases; D006602:Hexosyltransferases; D017351:N-Acetylglucosaminyltransferases; C020823:glycoprotein glycosyltransferase; C037649:N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase; D012799:Sialyltransferases; D000079:Acetaldehyde; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase