Comparative studies of glutathione reductase and lipoamide dehydrogenase.
1. Glutathione reductase and lipoamide dehydrogenase are structurally and mechanistically related flavoenzymes catalyzing various one and two electron transfer reactions between NAD(P)H and substrates with different structures. 2. The two enzymes differ in their coenzyme and functional specificities. Lipoamide dehydrogenase shows higher coenzyme preference while glutathione reductase displays greater functional specificity. 3. Binding preference of the two flavoenzymes for nicotinamide coenzymes is demonstrated by 31P-NMR spectroscopy. 4. The presence of arginines in glutathione reductase which is inactivated by phenyl glyoxal, is likely to be responsible for the NADPH-activity of glutathione reductase. 5. The substrate binding sites of the two enzymes are similar, though their functional details differ. 6. The active-site histidine of glutathione reductase functions primarily as the proton donor during catalysis. While the active-site histidine of lipoamide dehydrogenase stabilizes the thiolate anion intermediate and relays a proton in the catalytic process.
D000818:Animals; D008058:Dihydrolipoamide Dehydrogenase / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D009206:Myocardium / Q000201:enzymology; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013053:Spectrophotometry; D013552:Swine
D008058:Dihydrolipoamide Dehydrogenase; D005980:Glutathione Reductase