Mechanism of transfer of reduced nicotinamide adenine dinucleotide among dehydrogenases

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Abstract
The pathway for the transfer of NADH from one dehydrogenase (E1) to another dehydrogenase (E2) was investigated by studying the E2-catalyzed reduction of S2 by NADH. The experimental conditions are that the concentration of E1 exceeds that of NADH, which in turn is very much greater than E2; hence, the concentration of free (aqueous) NADH is exceedingly low. The rate of reduction of S2 will hence be very slow if unliganded aqueous NADH is required for the E2-catalyzed reaction. The results with 8 dehydrogenases [malate dehydrogenase, alanine dehydrogenase, sorbitol dehydrogenase, glutathione dehydrogenase, glyceraldehyde-3-phospate dehydrogenase, lactate dehydrogenase, liver alcohol dehydrogenase, .alpha.-glycerolphosphate dehydrogenase] are entirely consistent with the direct transfer of NADH between E1 and E2 whenever the 2 enzymes transfer H via opposite faces(A and B) of the nicotinamide ring. Whenever the 2 enzymes are both A or both B, NADH transfer occurs only via the aqueous solvent. Some mechanistic inferences and their possible physiological significance are discussed.