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Literature summary for 1.6.1.2 extracted from

  • Yin, F.; Sancheti, H.; Cadenas, E.
    Silencing of nicotinamide nucleotide transhydrogenase impairs cellular redox homeostasis and energy metabolism in PC12 cells (2012), Biochim. Biophys. Acta, 1817, 401-409.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.6.1.2

Activating Compound

Activating Compound Comment Organism Structure
additional information the proton gradient across the mitochondrial inner membrane strongly stimulates the forward reaction, i.e., the generation of NADPH Rattus norvegicus

Protein Variants

Protein Variants Comment Organism
additional information siRNA silencing or knockdown of NNT Rattus norvegicus

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrial inner membrane
-
 Rattus norvegicus 5743
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
NADPH + NAD+ Rattus norvegicus the proton gradient across the mitochondrial inner membrane strongly stimulates the forward reaction, i.e., the generation of NADPH NADP+ + NADH
-
 r

Organism

Organism UniProt Comment Textmining
Rattus norvegicus
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
PC-1 cell
-
 Rattus norvegicus
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pheochromocytoma cell
-
 Rattus norvegicus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
NADPH + NAD+
-
 Rattus norvegicus NADP+ + NADH
-
 r
NADPH + NAD+ the proton gradient across the mitochondrial inner membrane strongly stimulates the forward reaction, i.e., the generation of NADPH Rattus norvegicus NADP+ + NADH
-
 r

Synonyms

Synonyms Comment Organism
nicotinamide nucleotide transhydrogenase
-
 Rattus norvegicus
NNT
-
 Rattus norvegicus

General Information

General Information Comment Organism
malfunction small interfering RNA silencing of the enzyme in PC-12 cells results in decreased cellular NADPH levels, altered redox status of the cell in terms of decreased GSH/GSSG ratios and increased H2O2 levels, thus leading to an increased redox potential (a more oxidized redox state). NNT knockdown results in a decrease of oxidative phosphorylation while anaerobic glycolysis levels remain unchanged. Decreased oxidative phosphorylation was associated with 1. inhibition of mitochondrial pyruvate dehydrogenase and succinyl-CoA:3-oxoacid CoA transferase activity, 2. reduction of NADH availability, 3. decline of mitochondrial membrane potential, and 4. decrease of ATP levels Rattus norvegicus
physiological function crucial role of the enzyme in the maintenance of the redox environment. The proton gradient across the mitochondrial inner membrane strongly stimulates the forward reaction, i.e., the generation of NADPH. Under anaerobic and energy-deficient conditions, the reverse reaction catalyzed by NNT, i.e., the generation of NADH, also has transient effects on maintaining mitochondrial membrane potential through NADPH hydrolysis and H+ pumping, but the contribution of the backward reaction to the proton gradient is probably of little significance under physiological conditions. Oxidized cellular redox state is linked to a decline in cellular bioenergetics, overview Rattus norvegicus