TAILIEUCHUNG - Báo cáo khoa học: Glutamine and a-ketoglutarate as glutamate sources for glutathione synthesis in human erythrocytes

Glutathione (GSH) is an intracellular antioxidant synthesized from gluta-mate, cysteine and glycine. The human erythrocyte (red blood cell, RBC) requires a continuous supply of glutamate to prevent the limitation of GSH synthesis in the presence of sufficient cysteine, but the RBC membrane is almost impermeable to glutamate. | IFEBS Journal Glutamine and a-ketoglutarate as glutamate sources for glutathione synthesis in human erythrocytes Stephney Whillier1 Barbara Garcia1 Bogdan E. Chapman2 Philip W. Kuchel2 3 and Julia E. Raftos1 1 Department of BiologicalSciences Macquarie University Australia 2 Schoolof Molecular and MicrobialBiosciences University of Sydney Australia 3 Singapore Bioimaging Consortium A STAR Singapore Keywords erythrocyte glutamate glutamine glutathione a-ketoglutarate Correspondence J. E. Raftos Department of Biological Sciences Macquarie University Sydney NSW 2109 Australia Fax 61 02 9850 8245 Tel 61 02 9850 6275 E-mail Received 19 January 2011 revised 25 May 2011 accepted 21 June 2011 doi Glutathione GSH is an intracellular antioxidant synthesized from glutamate cysteine and glycine. The human erythrocyte red blood cell RBC requires a continuous supply of glutamate to prevent the limitation of GSH synthesis in the presence of sufficient cysteine but the RBC membrane is almost impermeable to glutamate. As optimal GSH synthesis is important in diseases associated with oxidative stress we compared the rate of synthesis using two potential glutamate substrates a-ketoglutarate and glutamine. Both substrates traverse the RBC membrane rapidly relative to many other metabolites. In whole RBCs partially depleted of intracellular GSH and glutamate 10 mM extracellular a-ketoglutarate but not 10 mM glutamine significantly increased the rate of GSH synthesis and ựmol- L RBC -1-mm-1 respectively compared with ựmol- L RBC -1-min-1 for RBCs without an external glutamate source. Mathematical modelling of the situation with mM extracellular glutamine returned a rate of glutamate production of ựmol- L RBC -1-min-1 while the initial rate for mM a-ketoglutarate was ựmol- L RBC _1-min-1. However with normal plasma concentrations the calculated rate of GSH synthesis was higher with .

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