Green tea catechins: inhibitors of glycerol-3-phosphate dehydrogenase.
Green tea catechins, especially (-)-epigallocatechin-3-gallate (EGCG), are known to regulate obesity and fat accumulation. We performed a kinetic analysis in a cell-free system to determine the mode of inhibition of glycerol-3-phosphate dehydrogenase (GPDH; EC 1.1.1.8) by EGCG. GPDH catalyzes the beta-nicotinamide adenine dinucleotide (NADH)-dependent reduction of dihydroxyacetone phosphate (DHAP) to yield glycerol-3-phosphate, which serves as one of the major precursors of triacylglycerols. We found that EGCG dose-dependently inhibited GPDH activity at a concentration of approximately 20 muM for 50 % inhibition. The IC (50) values of other green tea catechins, such as (-)-epicatechin, (-)-epicatechin-3-gallate, and (-)-epigallocatechin, were all above 100 microM. This suggests a catechin type-dependent effect. Based on double-reciprocal plots of the kinetic data, EGCG was a noncompetitive inhibitor of the GPDH substrates, NADH and DHAP, with respective inhibition constants (Ki) of 18 and 31 microM. Results of this study possibly support previous studies that EGCG mediates fat content.
Kao
Chung-Cheng
CC
Department of Emergency, Armed Forces Taoyuan General Hospital, Taoyuan, Taiwan.
Wu
Bo-Tsung
BT
Tsuei
Yi-Wei
YW
Shih
Li-Jane
LJ
Kuo
Yu-Liang
YL
Kao
Yung-Hsi
YH
D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D050536:Glycerol-3-Phosphate Dehydrogenase (NAD+) / Q000037:antagonists & inhibitors*; D014280:Triglycerides / Q000096:biosynthesis
D014280:Triglycerides; D002392:Catechin; C045651:epigallocatechin gallate; D050536:Glycerol-3-Phosphate Dehydrogenase (NAD+)