Modification of the glyoxalase system during the functional activation of human neutrophils.
The glyoxalase system catalyses the metabolism of methylglyoxal to D-lactic acid, via the intermediate S-D-lactoylglutathione. It is present in human neutrophils and undergoes a significant modification during functional activation--induction of chemotaxis, phagocytosis and degranulation. During the activation of neutrophils with serum-opsonised zymosan and the tumour-promoting phorbol diester 12-O-tetradecanoylphorbol 13-acetate, the activity of glyoxalase I increases and the activity of glyoxalase II decreases by 20-40% of their activities in resting cells, in the initial 10 min of the activation period. Determination of the Michaelis constant, Km, and the apparent maximum velocity, Vmax, for these enzymatic reactions indicates that the change in activity is due to a non-competitive activation and inhibition of glyoxalase I and glyoxalase II, respectively. This is consistent with a modification of the glyoxalase enzyme protein during the activation response. This modification occurs under aerobic and anaerobic incubation conditions. The concentration of S-D-lactoylglutathione increases approx. 100% of the resting cell concentration during the initial 10 min of the activation period. The presence of S-D-lactoylglutathione in neutrophils may be related to its ability to stimulate microtubule assembly.
Thornalley
P J
PJ
Department of Pharmaceutical Sciences, Aston University, Birmingham, U.K.
Bellavite
P
P
D002462:Cell Membrane / Q000201:enzymology; D005978:Glutathione / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D007791:Lactoylglutathione Lyase / Q000097:blood*; D008190:Lyases / Q000097:blood*; D009247:NADH, NADPH Oxidoreductases / Q000097:blood; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013869:Thiolester Hydrolases / Q000097:blood*; D015054:Zymosan / Q000494:pharmacology*; D000099301:Hydroxyacylglutathione Hydrolase
D005978:Glutathione; D007791:Lactoylglutathione Lyase; D008190:Lyases; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate; D013869:Thiolester Hydrolases; D015054:Zymosan; D000099301:Hydroxyacylglutathione Hydrolase