The human red blood cell glyoxalase system in diabetes mellitus.
Methylglyoxal and other alpha-oxoaldehydes are formed from glycolytic intermediates and may be involved in the development of diabetic microangiopathy. Glyoxalase I and glyoxalase II metabolise methylglyoxal to D-lactic acid, via the intermediate S-D-lactoylglutathione. The activities of the glyoxalase enzymes and the concentrations of methylglyoxal and S-D-lactoylglutathione were measured in erythrocytes of 45 control and 85 diabetic subjects (41 with retinopathy and 44 uncomplicated). The concentration of S-D-lactoylglutathione was increased in diabetic patients vs. controls (21.4 +/- 9.3 vs. 12.4 +/- 4.8 mumol/l, P less than 0.001), as was methylglyoxal (3.6 +/- 2.3 vs. 1.4 +/- 0.2 mumol/l, P less than 0.001). There were no significant differences in the activities of glyoxalase I and glyoxalase II between diabetic patients and controls. For insulin-dependent patients only, those without retinopathy had a higher activity of glyoxalase II than those with retinopathy (P less than 0.05). A group of age- and duration-matched insulin-dependent diabetic patients with retinopathy also had a higher activity of glyoxalase I compared with a group of diabetic patients without retinopathy (P less than 0.025). This study provides evidence for elevated concentrations of oxoaldehydes in diabetes mellitus which might have pathogenic significance.
Thornalley
P J
PJ
Pharmaceutical Sciences Institute, Aston University, Birmingham, U.K.
Hooper
N I
NI
Jennings
P E
PE
Florkowski
C M
CM
Jones
A F
AF
Lunec
J
J
Barnett
A H
AH
D000328:Adult; D003920:Diabetes Mellitus / Q000201:enzymology*; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology; D004912:Erythrocytes / Q000201:enzymology*; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000097:blood*; D008190:Lyases / Q000097:blood*; D008875:Middle Aged; D012016:Reference Values; D013869:Thiolester Hydrolases / Q000097:blood*; D000099301:Hydroxyacylglutathione Hydrolase
D007791:Lactoylglutathione Lyase; D008190:Lyases; D013869:Thiolester Hydrolases; D000099301:Hydroxyacylglutathione Hydrolase