Processing of protein glycation, oxidation and nitrosation adducts in the liver and the effect of cirrhosis.
OBJECTIVE
Plasma proteins are modified non-enzymatically in vivo by glycation, oxidation and nitrosation processes. Hepatic extraction of albumin glycated in vitro was reported but it is not clear if plasma proteins glycated in vivo also undergo hepatic extraction. We investigated the hepatic extraction of glycated, oxidised and nitrosated proteins in vivo.


METHODS
Protein glycation, oxidation and nitrosation marker residues and free adducts were determined in portal, hepatic and peripheral venous blood plasma of cirrhotic patients and hepatic and peripheral venous blood plasma (as a surrogate of portal venous blood) of control subjects by liquid chromatography-mass spectrometry.


RESULTS
There was no evidence for extraction of glycated, oxidised or nitrosated proteins or related free adducts by the liver in control subjects. There was limited extraction of methylglyoxal-modified proteins in cirrhotic patients and twofold increases in the concentrations of fructosyl-lysine and advanced glycation endproduct residues of plasma protein, with respect to controls. Remarkably, glyoxal-derived hydroimidazolone free adduct was increased 14-16-fold probably as a consequence of hepatic lipid peroxidation.


CONCLUSIONS
We found no evidence for hepatic extraction of glycated, oxidised and nitrosated proteins or related free adducts in subjects with normal liver function and limited extraction of methylglyoxal-modified protein in cirrhotic subjects.
Ahmed
Naila
N
Department of Biological Sciences, University of Essex, Wivenhoe Park, Central Campus, Colchester, Essex CO4 3SQ, UK.
Thornalley
Paul J
PJ
Lüthen
Reinhard
R
Häussinger
Dieter
D
Sebekova
Katarina
K
Schinzel
Reinhard
R
Voelker
Wolfram
W
Heidland
August
A
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood; D006031:Glycosylation; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000097:blood / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D015538:Nitrosation; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D011765:Pyruvaldehyde / Q000378:metabolism
D015415:Biomarkers; D001798:Blood Proteins; D017127:Glycation End Products, Advanced; C033186:fructosyl-lysine; D011765:Pyruvaldehyde; D008239:Lysine