The transhydrogenation between NADH and NADP is coupled to respiration and ATP hydrolysis and functions as a proton pump across the membrane. May play a role in reactive oxygen species (ROS) detoxification in the adrenal gland.
Using targeted exome sequencing, we identified mutations in NNT, an antioxidant defense gene, in individuals with familial glucocorticoid deficiency. In mice with Nnt loss, higher levels of adrenocortical cell apoptosis and impaired glucocorticoid production were observed. NNT knockdown in a human adrenocortical cell line resulted in impaired redox potential and increased reactive oxygen species (ROS) levels. Our results suggest that NNT may have a role in ROS detoxification in human adrenal glands.
Interacting selectively and non-covalently with nicotinamide adenine dinucleotide, a coenzyme involved in many redox and biosynthetic reactions; binding may be to either the oxidized form, NAD+, or the reduced form, NADH.
BACKGROUND: Transhydrogenase, located in the inner membranes of animal mitochondria and the cytoplasmic membranes of bacteria, couples the transfer of reducing equivalents between NAD(H) and NADP(H) to proton pumping. The protein comprises three subunits termed dI, dII and dIII. The dII component spans the membrane. The dI component, which contains the binding site for NAD(+)/NADH, and the dIII component, which has the binding site for NADP(+)/NADPH, protrude from the membrane. Proton pumping is probably coupled to changes in the binding affinities of dIII for NADP(+) and NADPH. RESULTS: The first X-ray structure of the NADP(H)-binding component, dIII, of human heart transhydrogenase is described here at 2.0 A resolution. It comprises a single domain resembling the classical Rossmann fold, but NADP(+) binds to dIII with a reversed orientation. The first betaalphabetaalphabeta motif of dIII contains a Gly-X-Gly-X-X-Ala/Val 'fingerprint', but it has a different function to that in the classical Rossmann structure. The nicotinamide ring of NADP(+) is located on a ridge where it is exposed to interaction with NADH on the dI subunit. Two distinctive features of the dIII structure are helix D/loop D, which projects from the beta sheet, and loop E, which forms a 'lid' over the bound NADP(+). CONCLUSIONS: Helix D/loop D interacts with the bound nucleotide and loop E, and probably interacts with the membrane-spanning dII. Changes in ionisation and conformation in helix D/loop D, resulting from proton translocation through dII, are thought to be responsible for the changes in affinity of dIII for NADP(+) and NADPH that drive the reaction.
Catalysis of the reaction: NADPH + H+ + NAD+ = NADP+ + NADH + H+. The reaction is A-specific (i.e. the pro-R hydrogen is transferred from the 4-position of reduced nicotinamide cofactor) with respect to NAD+ and B-specific (i.e. the pro-S hydrogen is transferred) with respect to NADP+.
Catalysis of the reaction: NADPH + H+ + NAD+ = NADP+ + NADH + H+, driving the transfer of a solute or solutes from one side of a membrane to the other. In the course of the reaction (left to right) one H atom is transferred from inside the cell to outside. The reaction is B-specific (i.e. the pro-S hydrogen is transferred from the 4-position of reduced nicotinamide cofactor) with respect to both NAD+ and NADP+.
Pyridine nucleotide transhydrogenases (E.C.1.6.1.1) are integral proteins of the inner mitochondrial membrane. These enzymes are part of the energy-transfer system of the respiratory chain and specifically catalyze the transfer of a hydride ion between nicotinamide adenine dinucleotide, NAD(H), and oxidized nicotinamide dinucleotide phosphate, NADP(H). Here we report the sequence of full-length cDNA clone containing the coding sequence for human mitochondrial nicotinamide nucleotide transhydrogenase. The characterized cDNA contains an insert of 4,232 base pairs with a 91% sequence identity to a previously characterized bovine transhydrogenase cDNA. The deduced human polypeptide sequence displays a high degree of sequence similarity, 97%, to the bovine polypeptide and a comparison of the two sequences is presented.
Interacting selectively and non-covalently with nicotinamide-adenine dinucleotide phosphate, a coenzyme involved in many redox and biosynthetic reactions; binding may be to either the oxidized form, NADP+, or the reduced form, NADPH.
BACKGROUND: Transhydrogenase, located in the inner membranes of animal mitochondria and the cytoplasmic membranes of bacteria, couples the transfer of reducing equivalents between NAD(H) and NADP(H) to proton pumping. The protein comprises three subunits termed dI, dII and dIII. The dII component spans the membrane. The dI component, which contains the binding site for NAD(+)/NADH, and the dIII component, which has the binding site for NADP(+)/NADPH, protrude from the membrane. Proton pumping is probably coupled to changes in the binding affinities of dIII for NADP(+) and NADPH. RESULTS: The first X-ray structure of the NADP(H)-binding component, dIII, of human heart transhydrogenase is described here at 2.0 A resolution. It comprises a single domain resembling the classical Rossmann fold, but NADP(+) binds to dIII with a reversed orientation. The first betaalphabetaalphabeta motif of dIII contains a Gly-X-Gly-X-X-Ala/Val 'fingerprint', but it has a different function to that in the classical Rossmann structure. The nicotinamide ring of NADP(+) is located on a ridge where it is exposed to interaction with NADH on the dI subunit. Two distinctive features of the dIII structure are helix D/loop D, which projects from the beta sheet, and loop E, which forms a 'lid' over the bound NADP(+). CONCLUSIONS: Helix D/loop D interacts with the bound nucleotide and loop E, and probably interacts with the membrane-spanning dII. Changes in ionisation and conformation in helix D/loop D, resulting from proton translocation through dII, are thought to be responsible for the changes in affinity of dIII for NADP(+) and NADPH that drive the reaction.
A metabolic process that results in the removal or addition of one or more electrons to or from a substance, with or without the concomitant removal or addition of a proton or protons.
BACKGROUND: Transhydrogenase, located in the inner membranes of animal mitochondria and the cytoplasmic membranes of bacteria, couples the transfer of reducing equivalents between NAD(H) and NADP(H) to proton pumping. The protein comprises three subunits termed dI, dII and dIII. The dII component spans the membrane. The dI component, which contains the binding site for NAD(+)/NADH, and the dIII component, which has the binding site for NADP(+)/NADPH, protrude from the membrane. Proton pumping is probably coupled to changes in the binding affinities of dIII for NADP(+) and NADPH. RESULTS: The first X-ray structure of the NADP(H)-binding component, dIII, of human heart transhydrogenase is described here at 2.0 A resolution. It comprises a single domain resembling the classical Rossmann fold, but NADP(+) binds to dIII with a reversed orientation. The first betaalphabetaalphabeta motif of dIII contains a Gly-X-Gly-X-X-Ala/Val 'fingerprint', but it has a different function to that in the classical Rossmann structure. The nicotinamide ring of NADP(+) is located on a ridge where it is exposed to interaction with NADH on the dI subunit. Two distinctive features of the dIII structure are helix D/loop D, which projects from the beta sheet, and loop E, which forms a 'lid' over the bound NADP(+). CONCLUSIONS: Helix D/loop D interacts with the bound nucleotide and loop E, and probably interacts with the membrane-spanning dII. Changes in ionisation and conformation in helix D/loop D, resulting from proton translocation through dII, are thought to be responsible for the changes in affinity of dIII for NADP(+) and NADPH that drive the reaction.
The directed movement of protons (hydrogen ions) into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
BACKGROUND: Transhydrogenase, located in the inner membranes of animal mitochondria and the cytoplasmic membranes of bacteria, couples the transfer of reducing equivalents between NAD(H) and NADP(H) to proton pumping. The protein comprises three subunits termed dI, dII and dIII. The dII component spans the membrane. The dI component, which contains the binding site for NAD(+)/NADH, and the dIII component, which has the binding site for NADP(+)/NADPH, protrude from the membrane. Proton pumping is probably coupled to changes in the binding affinities of dIII for NADP(+) and NADPH. RESULTS: The first X-ray structure of the NADP(H)-binding component, dIII, of human heart transhydrogenase is described here at 2.0 A resolution. It comprises a single domain resembling the classical Rossmann fold, but NADP(+) binds to dIII with a reversed orientation. The first betaalphabetaalphabeta motif of dIII contains a Gly-X-Gly-X-X-Ala/Val 'fingerprint', but it has a different function to that in the classical Rossmann structure. The nicotinamide ring of NADP(+) is located on a ridge where it is exposed to interaction with NADH on the dI subunit. Two distinctive features of the dIII structure are helix D/loop D, which projects from the beta sheet, and loop E, which forms a 'lid' over the bound NADP(+). CONCLUSIONS: Helix D/loop D interacts with the bound nucleotide and loop E, and probably interacts with the membrane-spanning dII. Changes in ionisation and conformation in helix D/loop D, resulting from proton translocation through dII, are thought to be responsible for the changes in affinity of dIII for NADP(+) and NADPH that drive the reaction.
The chemical reactions and pathways involving a reactive oxygen species, any molecules or ions formed by the incomplete one-electron reduction of oxygen. They contribute to the microbicidal activity of phagocytes, regulation of signal transduction and gene expression, and the oxidative damage to biopolymers.
Evidence
1:
Inferred from Mutant PhenotypeUniProtKB
Using targeted exome sequencing, we identified mutations in NNT, an antioxidant defense gene, in individuals with familial glucocorticoid deficiency. In mice with Nnt loss, higher levels of adrenocortical cell apoptosis and impaired glucocorticoid production were observed. NNT knockdown in a human adrenocortical cell line resulted in impaired redox potential and increased reactive oxygen species (ROS) levels. Our results suggest that NNT may have a role in ROS detoxification in human adrenal glands.
A nearly universal metabolic pathway in which the acetyl group of acetyl coenzyme A is effectively oxidized to two CO2 and four pairs of electrons are transferred to coenzymes. The acetyl group combines with oxaloacetate to form citrate, which undergoes successive transformations to isocitrate, 2-oxoglutarate, succinyl-CoA, succinate, fumarate, malate, and oxaloacetate again, thus completing the cycle. In eukaryotes the tricarboxylic acid is confined to the mitochondria. See also glyoxylate cycle.
BACKGROUND: Transhydrogenase, located in the inner membranes of animal mitochondria and the cytoplasmic membranes of bacteria, couples the transfer of reducing equivalents between NAD(H) and NADP(H) to proton pumping. The protein comprises three subunits termed dI, dII and dIII. The dII component spans the membrane. The dI component, which contains the binding site for NAD(+)/NADH, and the dIII component, which has the binding site for NADP(+)/NADPH, protrude from the membrane. Proton pumping is probably coupled to changes in the binding affinities of dIII for NADP(+) and NADPH. RESULTS: The first X-ray structure of the NADP(H)-binding component, dIII, of human heart transhydrogenase is described here at 2.0 A resolution. It comprises a single domain resembling the classical Rossmann fold, but NADP(+) binds to dIII with a reversed orientation. The first betaalphabetaalphabeta motif of dIII contains a Gly-X-Gly-X-X-Ala/Val 'fingerprint', but it has a different function to that in the classical Rossmann structure. The nicotinamide ring of NADP(+) is located on a ridge where it is exposed to interaction with NADH on the dI subunit. Two distinctive features of the dIII structure are helix D/loop D, which projects from the beta sheet, and loop E, which forms a 'lid' over the bound NADP(+). CONCLUSIONS: Helix D/loop D interacts with the bound nucleotide and loop E, and probably interacts with the membrane-spanning dII. Changes in ionisation and conformation in helix D/loop D, resulting from proton translocation through dII, are thought to be responsible for the changes in affinity of dIII for NADP(+) and NADPH that drive the reaction.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
My favorites 
My labels 
Login
