Proton-translocating Transhydrogenase: An Update of Unsolved and Controversial Issues

J Bioenerg Biomembr. 2008 Oct;40(5):463-73. doi: 10.1007/s10863-008-9170-x. Epub 2008 Oct 30.


Proton-translocating transhydrogenases, reducing NADP(+) by NADH through hydride transfer, are membrane proteins utilizing the electrochemical proton gradient for NADPH generation. The enzymes have important physiological roles in the maintenance of e.g. reduced glutathione, relevant for essentially all cell types. Following X-ray crystallography and structural resolution of the soluble substrate-binding domains, mechanistic aspects of the hydride transfer are beginning to be resolved. However, the structure of the intact enzyme is unknown. Key questions regarding the coupling mechanism, i.e., the mechanism of proton translocation, are addressed using the separately expressed substrate-binding domains. Important aspects are therefore which functions and properties of mainly the soluble NADP(H)-binding domain, but also the NAD(H)-binding domain, are relevant for proton translocation, how the soluble domains communicate with the membrane domain, and the mechanism of proton translocation through the membrane domain.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Catalytic Domain
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • NAD / metabolism
  • NADP / metabolism
  • NADP Transhydrogenases / chemistry*
  • NADP Transhydrogenases / genetics
  • NADP Transhydrogenases / metabolism*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Proton Pumps / chemistry
  • Proton Pumps / metabolism


  • Proton Pumps
  • NAD
  • NADP
  • NADP Transhydrogenases