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Nicotinamide adenine dinucleotide (NAD+/NADH)

Nicotinamide adenine dinucleotide (NAD+) definition

Nicotinamide adenine dinucleotide or NAD+ is the cofactor or coenzyme for most dehydrogenases. NAD+ is the oxidised form of NADH and vice versa, NADH id the reduced form of NAD+. NAD+ is a source for NADP+ biosynthesis by NAD+-kinase with subsequent energy transduction from ATP.

Nicotinamide adenine dinucleotide (NAD+) basic

  • Molecular formula: C21H27N7O14P2
  • Molecular weight: 663.425 Da
  • IUPAC name 1: [(2R,3R,4S)-5-(6-aminopurin-9-yl)-3,4-dihydroxy-oxolan-2-yl]methoxy-[[(3R,4S)-4-(5-carbamoylpyridin-1-yl)-3,4-dihydroxy-oxolan-2-yl]methoxy-oxido-phosphoryl]oxy-phosphinic acid
  • IUPAC name 2: [[(2R,3S,4R,5R)-5-(5-aminocarbonylpyridin-1-yl)-3,4-dihydroxy-oxolan-2-yl]methoxy-oxido-phosphoryl]oxy-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxy-oxolan-2-yl]methoxy]phosphinic acid
  • Appearance: White crystalline solid

Nicotinamide adenine dinucleotide (NAD+) structure

Nicotinamide adenine dinucleotide Nicotinamide adenine dinucleotide stick model Nicotinamide adenine dinucleotide space filling model Nicotinamide adenine dinucleotide VDW model Nicotinamide adenine dinucleotide solvent accesible surface

Different representation of the Nicotinamide adenine dinucleotide (NAD+) structure. All structures were derived from the NAD+ coordinates from the structure of Aldehyde Dehydrogenase from Bovine mitochondria complex with NAD and Samarium (1A4Z.pdb). Click preview to see full resolution stereo picture.

Nicotinamide adenine dinucleotide (NAD+) synthesis pathway

In living organisms NAD+ can be synthesized by two different pathways. These pathways are merged by formation of nicotinate D-ribonucleotide. First pathway, also called kynurenine pathway is started from essential amino acid Tryptophan. Lack of Tryptophan on the diet can cause the Nicotinamide deficiently disease pellagra. Second pathway is started from Vitamin B3 (niacin, nicotinic acid). This vitamin is also essential.

Tryptophan pathway


L-Tryptophan to N-Formyl-L-kynurenine by tryptophan 2,3-dioxygenase, EC 1.13.11.11 L-Tryptophan -> N-Formyl-L-kynurenine catalyzed by tryptophan 2,3-dioxygenase, EC 1.13.11.11 (other names tryptophanase, indoleamine 2,3-dioxygenase)
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N-Formyl-L-kynurenine to L-kynurenine by Kynurenine formylase, EC 3.5.1.9 N-Formyl-L-kynurenine to L-kynurenine catalyzed by Kynurenine formylase, EC 3.5.1.9
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Conversion of L-Kynurenine to 3-Hydroxyanthranilic acid can be done by two different ways:
via 3-Hydroxykynurenine
from L-Kynurenine to 3-Hydroxykynurenine by Kynurenine 3-hydroxylase, EC 1.14.13.9 L-Kynurenine -> 3-Hydroxykynurenine catalyzed by Kynurenine 3-hydroxylase, EC 1.14.13.9
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from 3-Hydroxykynurenine to 3-Hydroxyanthranilic acid by Kynureninase, EC 3.7.1.3 3-Hydroxykynurenine -> 3-Hydroxyanthranilic acid catalyzed by Kynureninase, EC 3.7.1.3
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and via Anthranilic acid
from L-Kynurenine to Anthranilic acid by Kynureninase, EC 3.7.1.3 L-Kynurenine -> Anthranilic acid catalyzed by Kynureninase, EC 3.7.1.3
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from Anthranilic acid to 3-Hydroxyanthranilic acid by 3-hydroxyanthranilate oxygenase EC 1.13.1.6 Anthranilic acid -> 3-Hydroxyanthranilic acid catalyzed by 3-hydroxyanthranilate oxygenase, EC 1.13.1.6
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After this small difference in the pathway, the last steps are common:
from 3-Hydroxyanthranilic acid to 2-amino-3-carboxymuconate semialdehyde by 3-Hydroxyanthranilic acid oxidase, EC 1.13.11.6 3-Hydroxyanthranilic acid -> 2-amino-3-carboxymuconate semialdehyde catalyzed by 3-Hydroxyanthranilic acid oxidase, EC 1.13.11.6
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from 2-amino-3-carboxymuconate semialdehyde to Quinolinic acid 2-amino-3-carboxymuconate semialdehyde -> Quinolinic acid, This is a non-enzymatic spontaneous step of catalysis
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from pyridine-2,3-dicarboxylate + 5-phospho-alpha-D-ribose 1-diphosphate to nicotinate D-ribonucleotide + diphosphate + CO2 by cotinate-nucleotide diphosphorylase, EC 2.4.2.19 pyridine-2,3-dicarboxylate (Quinolinic acid) + 5-phospho-alpha-D-ribose 1-diphosphate -> nicotinate D-ribonucleotide + diphosphate + CO2, catalyzed by nicotinate-nucleotide diphosphorylase (nicotinate-nucleotide:diphosphate phospho-alpha-D-ribosyltransferase), EC 2.4.2.19
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Vitamin B3 (niacin, nicotinic acid) pathway

This pathway is started from Vitamin B3 (nicotinate).
from nicotinate + 5-phosphoribosyl-1-pyrophosphate to nicotinate D-ribonucleotide + diphosphate Nicotinate (Vitabin B3) + 5-phosphoribosyl-1-pyrophosphate -> nicotinate D-ribonucleotide + diphosphate, catalyzed by nicotinate phosphoribosyltransferase (icotinate-nucleotide:diphosphate phospho-alpha-D-ribosyltransferase), EC 2.4.2.11
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Common steps of NAD+ biosynthesis

.
from Nicotinate D-ribonucleotide to deamido-NAD+ by nicotinate-nucleotide adenylyltransferase EC 2.7.7.18 Nicotinate D-ribonucleotide + ATP -> deamido-NAD+ + diphosphate, catalyzed by nicotinate-nucleotide adenylyltransferase (ATP:nicotinate-ribonucleotide adenylyltransferase), EC 2.7.7.18
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from deamido-NAD+ to NAD+ by EC 6.3.5.1 or by EC 6.3.1.5 deamido-NAD+ -> NAD+
This reaction can be catalysed by two different enzymes :
  1. deamido-NAD+:L-glutamine amido-ligase (AMP-forming) EC 6.3.5.1 or NAD+ synthase (glutamine-hydrolysing) via reaction:
    ATP + deamido-NAD+ + L-glutamine + H2O => AMP + diphosphate + NAD+ + L-glutamate
  2. deamido-NAD+:ammonia ligase (AMP-forming) EC 6.3.1.5 or NAD+ synthase via reaction:
    ATP + deamido-NAD+ + NH3 => AMP + diphosphate + NAD+
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NAD+ and NADH


Difference between NAD+ and NADH Structural formula of NAD+ and NADH. The difference in hydrogen atoms in the Nicotinamide moiety is shown.
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The overall involvement of Nicotinamide adenine dinucleotide phosphate into the living cell processes is illustrated on Nicotinamide nucleotides in catabolism and biosynthesis scheme.

The reaction of NADH oxidation to NAD+ mainly presents in the electron-transport chain pathways:
The first reaction in the electron-transport chain is reaction NADH + H+ + ubiquinone => NAD+ + ubiquinol catalyzed by NADH:ubiquinone oxidoreductase EC 1.6.5.3 (other names: NADH2 dehydrogenase (ubiquinone); NADH-Q6 oxidoreductase; electron transfer complex I; NADH:ubiquinone oxidoreductase complex; NADH-ubiquinone-1 reductase; reduced nicotinamide adenine dinucleotide-coenzyme Q reductase; NADH-ubiquinone reductase; NADH-ubiquinone oxidoreductase; NADH-CoQ oxidoreductase; NADH-coenzyme Q reductase; NADH-CoQ reductase; NADH coenzyme Q1 reductase; NADH-coenzyme Q oxidoreductase; mitochondrial electron transport complex I; mitochondrial electron transport complex 1; DPNH-ubiquinone reductase; DPNH-coenzyme Q reductase; dihydronicotinamide adenine dinucleotide-coenzyme Q reductase; complex I (NADH:Q1 oxidoreductase); ubiquinone reductase; type 1 dehydrogenase; complex 1 dehydrogenase; coenzyme Q reductase; complex I (electron transport chain); complex I (mitochondrial electron transport); NADH dehydrogenase (ubiquinone)).

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