Nicotinamide Nucleotide Transhydrogenase

Abstract

Membrane-bound nicotinamide nucleotide transhydrogenase is located in the bacterial plasma membrane and mitochondrial inner membrane and catalyzes the reversible reduction of NADP+ by NADH. The reaction is linked to the electrochemical proton gradient across the membrane, generating NADPH essential for, for example, detoxification of peroxides. In its isolated form, the enzyme is a proton pump where proton translocation is driven by the catalytic reaction, mediated by conformational changes. Extensive investigations of the structure–function relationships, especially of the substrate-binding domains, have established their structures and roles. The membrane domain, in which the proton channel resides, has been structurally predicted, but remains to be determined structurally at the atomic level. Models for the molecular proton translocation mechanism are therefore beginning to emerge.