NNT dimer transfers proton from NADPH to NAD+

Stable Identifier
R-HSA-450971
Type
Reaction [transition]
Species
Homo sapiens
Compartment
mitochondrion
Synonyms
H(+)(in) + NAD(+) + NADPH = H(+)(out) + NADH + NADP(+)
ReviewStatus
5/5
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NNT dimer transfers proton from NADPH to NAD+
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NNT (nicotinamide nucleotide transhydrogenase) associated with the inner mitochondrial membrane catalyzes the reaction of mitochondrial NADPH and NAD+ to form NADP+ and NADH. The reaction is coupled to the translocation of a proton across the inner mitochondrial membrane into the mitochondrial matrix (Arkblad et al., 1996; White et al., 2000). The active form of NNT is inferred to be a homodimer based on the known structure of its bovine homolog (Yamaguchi & Hatefi, 1991) and the structure of the ovine homolog (Kampjut & Sazanow, 2019). Mutations in NNT can lead to glucocorticoid deficiency (GCCD4; MIM:614736; reviewed in Francisco et al., 2021).
Literature References
PubMed ID Title Journal Year
8616157 The cDNA sequence of proton-pumping nicotinamide nucleotide transhydrogenase from man and mouse

Arkblad, EL, Betsholtz, C, Rydström, J

Biochim Biophys Acta 1996
2005110 Mitochondrial energy-linked nicotinamide nucleotide transhydrogenase. Membrane topography of the bovine enzyme

Yamaguchi, M, Hatefi, Y

J Biol Chem 1991
34155914 Mitochondrial NAD(P)+ Transhydrogenase: From Molecular Features to Physiology and Disease

Francisco, A, Figueira, TR, Castilho, RF

Antioxid Redox Signal 2022
10673423 The high-resolution structure of the NADP(H)-binding component (dIII) of proton-translocating transhydrogenase from human heart mitochondria

White, SA, Peake, SJ, McSweeney, S, Leonard, G, Cotton, NP, Jackson, JB

Structure 2000
31462775 Structure and mechanism of mitochondrial proton-translocating transhydrogenase

Kampjut, D, Sazanov, LA

Nature 2019
Participants
Input
Output
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as an event of
Catalyst Activity

NAD(P)+ transhydrogenase (Si-specific) activity of NNT dimer [mitochondrial inner membrane]

Physical Entity
NNT dimer [mitochondrial inner membrane] (Homo sapiens)
Activity
NAD(P)+ transhydrogenase (Si-specific) activity (GO:0003957)
Orthologous Events
NNT dimer transfers proton from NADPH to NAD+ (Bos taurus)
NNT dimer transfers proton from NADPH to NAD+ (Caenorhabditis elegans)
NNT dimer transfers proton from NADPH to NAD+ (Canis familiaris)
NNT dimer transfers proton from NADPH to NAD+ (Danio rerio)
NNT dimer transfers proton from NADPH to NAD+ (Dictyostelium discoideum)
NNT dimer transfers proton from NADPH to NAD+ (Gallus gallus)
NNT dimer transfers proton from NADPH to NAD+ (Mus musculus)
NNT dimer transfers proton from NADPH to NAD+ (Plasmodium falciparum)
NNT dimer transfers proton from NADPH to NAD+ (Rattus norvegicus)
NNT dimer transfers proton from NADPH to NAD+ (Xenopus tropicalis)
Cross References
RHEA
Authored
D'Eustachio, P  (2009-12-26)
Reviewed
Hill, DP  (2024-02-15)
Created
D'Eustachio, P  (2009-12-25)
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