Nicotinamide nucleotide transhydrogenase: a model for utilization of substrate binding energy for proton translocation

Abstract

The energy-transducing nicotinamide nucleotide transhydrogenases of mammalian mitochondria and bacteria are structurally related membrane-bound enzymes that catalyze the direct transfer of a hydride ion between NAD(H) and NADP(H) in a reaction that is coupled to transmembrane proton translocation. The protonmotive force alters the affinity of the transhydrogenase for substrates, accelerates the rate of hydride ion transfer from NADH to NADP, and shifts the equilibrium of this reaction toward NADPH formation. Transhydrogenation in the reverse direction from NADPH to NAD is accompanied by outward proton translocation and formation of a protonmotive force. In reverse transhydrogenation, the enzyme utilizes substrate binding energy for proton pumping. Therefore, with regard to the mechanism of energy transduction, the transhydrogenase works according to the same principles as the ATP synthase complex of mitochondria and bacteria, the proton and cation ATPases, and possibly certain redox-linked proton pumps. However, the relatively simple structure of the transhydrogenase recommends it as a model for study of the utilization of binding energy for vectorial translocation of protons and other cations.