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Literature summary for 1.6.1.2 extracted from

  • Gameiro, P.A.; Laviolette, L.A.; Kelleher, J.K.; Iliopoulos, O.; Stephanopoulos, G.
    Cofactor balance by nicotinamide nucleotide transhydrogenase (NNT) coordinates reductive carboxylation and glucose catabolism in the tricarboxylic acid (TCA) cycle (2013), J. Biol. Chem., 288, 12967-12977.
    View publication on PubMedView publication on EuropePMC

Protein Variants

Protein Variants Comment Organism
additional information overexpression and knockdown of the enzyme in carcinoma cells, phenotypes, overview Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrial inner membrane
-
Mus musculus 5743
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
NADPH + NAD+ Mus musculus
-
NADP+ + NADH
-
r
NADPH + NAD+ Mus musculus C57/BL6J
-
NADP+ + NADH
-
r

Organism

Organism UniProt Comment Textmining
Mus musculus
-
-
-
Mus musculus C57/BL6J
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
melanoma cell
-
Mus musculus
-
RCC 786-O cell
-
Mus musculus
-
renal carcinoma cell
-
Mus musculus
-
SK-MEL-5 cell
-
Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
NADPH + NAD+
-
Mus musculus NADP+ + NADH
-
r
NADPH + NAD+
-
Mus musculus C57/BL6J NADP+ + NADH
-
r

Synonyms

Synonyms Comment Organism
nicotinamide nucleotide transhydrogenase
-
Mus musculus
NNT
-
Mus musculus

General Information

General Information Comment Organism
malfunction knockdown of the enzyme inhibits the contribution of glutamine to the tricarbonic acid cycle and activates glucose catabolism in SkMel5 melanoma cells. The increase in glucose oxidation partially occurs through pyruvate carboxylase and renders NNT knockdown cells more sensitive to glucose deprivation. Importantly, knocking down NNT inhibits reductive carboxylation in SkMel5 and 786-O renal carcinoma cells. Overexpression of NNT is sufficient to stimulate glutamine oxidation and reductive carboxylation, whereas it inhibits glucose catabolism in the TCA cycle, with impairment of the NAD(P)H/NAD(P)+ ratios Mus musculus
physiological function nicotinamide nucleotide transhydrogenase is a mitochondrial enzyme that transfers reducing equivalents from NADH to NADPH Mus musculus