The effect of phenazine methosulphate on intermediary pathways of glucose metabolism in the lens at different glycaemic levels.
In this study changes in alternative pathways of glucose metabolism are examined in the rat lens using radiolabelled glucose in a 1 hr in vitro incubation of 50 mM or 10 mM glucose with or without 0.1 mM phenazine methosulphate (PMS). PMS which reoxidizes NADPH ensures that the pentose phosphate pathway (PPP) is not limited by the supply of NADP+. The data shows that maximal activation of the PPP (with PMS) is 40% greater at high glucose concentrations than normal glucose. This difference in maximal stimulation may be explained by the increase glucose uptake in the hyperglycaemic incubation. In the high-glucose incubation with PMS, hexokinase activity and the glucose 6-phosphate pool is not limiting for the PPP. Under these conditions, PMS alter the NAD+/NADH and NADP+/NADPH ratio. The change in the redox state alters the flux through the polyol pathway, the glycerol 3-phosphate shuttle and the glycolytic control sites, glyceraldehyde 3-phosphate, pyruvate and lactate dehydrogenases. These results are discussed in relation to hyperglycaemia-induced oxidative stress.
Muirhead
R P
RP
Department of Biochemistry and Molecular Biology, University College London, U.K.
Hothersall
J S
JS
D000818:Animals; D003958:Diamide / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006943:Hyperglycemia / Q000378:metabolism; D007908:Lens, Crystalline / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008773:Methylphenazonium Methosulfate / Q000494:pharmacology*; D009249:NADP / Q000378:metabolism*; D010427:Pentose Phosphate Pathway / Q000187:drug effects*; D010545:Peroxides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020122:tert-Butylhydroperoxide
D010545:Peroxides; D003958:Diamide; D008773:Methylphenazonium Methosulfate; D009249:NADP; D020122:tert-Butylhydroperoxide; D005947:Glucose