Accepted name: proton-translocating NAD(P)+ transhydrogenase
Reaction: NADPH + NAD+ + H+[side 1] = NADP+ + NADH + H+[side 2]
Other name(s): pntA (gene name); pntB (gene name); NNT (gene name)
Systematic name: NADPH:NAD+ oxidoreductase (H+-transporting)
Comments: The enzyme is a membrane bound proton-translocating pyridine nucleotide transhydrogenase that couples the reversible reduction of NADP by NADH to an inward proton translocation across the membrane. In the bacterium Escherichia coli the enzyme provides a major source of cytosolic NADPH. Detoxification of reactive oxygen species in mitochondria by glutathione peroxidases depends on NADPH produced by this enzyme.
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2.  Clarke, D.M. and Bragg, P.D. Purification and properties of reconstitutively active nicotinamide nucleotide transhydrogenase of Escherichia coli. Eur. J. Biochem. 149 (1985) 517–523. [PMID: 3891338]
3.  Glavas, N.A., Hou, C. and Bragg, P.D. Involvement of histidine-91 of the β subunit in proton translocation by the pyridine nucleotide transhydrogenase of Escherichia coli. Biochemistry 34 (1995) 7694–7702. [PMID: 7779816]
4.  Sauer, U., Canonaco, F., Heri, S., Perrenoud, A. and Fischer, E. The soluble and membrane-bound transhydrogenases UdhA and PntAB have divergent functions in NADPH metabolism of Escherichia coli. J. Biol. Chem. 279 (2004) 6613–6619. [PMID: 14660605]
5.  Bizouarn, T., Fjellstrom, O., Meuller, J., Axelsson, M., Bergkvist, A., Johansson, C., Goran Karlsson, B. and Rydstrom, J. Proton translocating nicotinamide nucleotide transhydrogenase from E. coli. Mechanism of action deduced from its structural and catalytic properties. Biochim. Biophys. Acta 1457 (2000) 211–228. [PMID: 10773166]
6.  White, S.A., Peake, S.J., McSweeney, S., Leonard, G., Cotton, N.P. and Jackson, J.B. The high-resolution structure of the NADP(H)-binding component (dIII) of proton-translocating transhydrogenase from human heart mitochondria. Structure 8 (2000) 1–12. [PMID: 10673423]
7.  Johansson, T., Oswald, C., Pedersen, A., Tornroth, S., Okvist, M., Karlsson, B.G., Rydstrom, J. and Krengel, U. X-ray structure of domain I of the proton-pumping membrane protein transhydrogenase from Escherichia coli. J. Mol. Biol. 352 (2005) 299–312. [PMID: 16083909]
8.  Meimaridou, E., Kowalczyk, J., Guasti, L., Hughes, C.R., Wagner, F., Frommolt, P., Nurnberg, P., Mann, N.P., Banerjee, R., Saka, H.N., Chapple, J.P., King, P.J., Clark, A.J. and Metherell, L.A. Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. Nat. Genet. 44 (2012) 740–742. [PMID: 22634753]
[EC created 2015 as EC, transferred 2018 to EC]