Possible Interaction: NAD and Alpha-Ketoglutarate

“Covalent adducts of NAD+ with pyruvate and 2-oxoglutarate have been reported to inhibit differentially the activities of bovine glutamate dehydrogenase (GDH) towards these two oxoacid substrates, implying separate active sites.”

“ NAD caused the rise in oxidation intensity of isocitrate, cis-aconitate, oxalacetate, alpha-ketoglutarate , malate, fumarate and pyruvate while NADP--of isocitrate and citrate.”

“Binding of phosphate to the enzyme with a Kd of about 20 mM or binding of pyrophosphate or tripolyphosphate with a Dd of about 2.5 mM enhances the binding of spin-labelled NAD+ in the presence of 2-oxoglutarate.”

“All compounds inhibited nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate and alpha-ketoglutarate selectively, whereas NAD-independent oxidation of succinate remained unaltered.”

“Paired combinations of glutarate or 2-oxoglutarate and NAD+ gave slightly better protection than the separate components, but the most effective combination was 40 mM 2-oxoglutarate with 1 mM NADH (85% activity at equilibrium).”

“State 3 malate and 2-oxoglutarate oxidation rates with turnip mitochondria were stimulated 25 to 40% by external NAD.”

“With purified beetroot mitochondria, state 3 malate and 2-oxoglutarate oxidation rates were only marginally increased (10-15%) by the addition of NAD but after NAD-depletion treatments this stimulation increased to 55%.”

“The most marked decrease in the rate of inactivation (about 10-fold) is provided by the combined addition of NAD+ and 2-oxoglutarate , suggesting that modification takes place in the region of the active site.”

“In the direction of reductive condensation of alpha-ketoglutarate and lysine, saccharopine dehydrogenase (N6-(glutar-2-yl)-L-lysine NAD oxidoreductase (lysine-forming) is inhibited by high concentrations of alpha-ketoglutarate and lysine, but not by NADH.”