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 | Comment | Organism |
---|---|---|
additional information | siRNA silencing or knockdown of NNT | Rattus norvegicus |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
mitochondrial inner membrane | - |
Rattus norvegicus | 5743 | - |
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 | UniProt | Comment | Textmining |
---|---|---|---|
Rattus norvegicus | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
PC-1 cell | - |
Rattus norvegicus | - |
pheochromocytoma cell | - |
Rattus norvegicus | - |
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 | Comment | Organism |
---|---|---|
nicotinamide nucleotide transhydrogenase | - |
Rattus norvegicus |
NNT | - |
Rattus norvegicus |
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 |