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.
Pharmaceutical Sciences Institute, Aston University, Birmingham, U.K.
P J
PJ
Thornalley
N I
NI
Hooper
P E
PE
Jennings
C M
CM
Florkowski
A F
AF
Jones
J
J
Lunec
A H
AH
Barnett
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