NAD Biosynthesis II (from tryptophan) (Homo sapiens)

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spontaneousNADSYN1L-Glutamic acidL-GlutamineHAAOFormic acidWaterNicotinic acidadenine dinucleotidePyrophosphatepyrophosphatePhosphoribosylpyrophosphateNicotinic acidmononucleotideL-AlanineL-3-HydroxykynurenineNMNAT1N'-FormylkynurenineNADWaterKYNUOxygenPyrophosphateAdenosinetriphosphateHydrogen Ion2-Amino-3-carboxymuconicacid semialdehydeAdenosinemonophosphateWater3-Hydroxyanthranilic acidL-TryptophanNADPKMOAdenosinetriphosphateQuinolinic acidQPRTTDO2Carbon dioxideL-KynurenineAFMIDNADPHHydrogen IonWaterHydrogen IonHydrogen IonHydrogen IonHydrogen IonOxygenHydrogen IonWaterHydrogen IonHydrogen IonHydrogen IonOxygenHydrogen IonHydrogen Ion


As a general rule, most prokaryotes utilize the aspartate de novo pathway, in which the nicotinate moiety of NAD is synthesized from aspartate (see NAD biosynthesis I (from aspartate)). In eukaryotes, the de novo pathway starts with tryptophan (this pathway).

The role of tryptophan as a precursor in eukaryotic NAD biosynthesis was first suggested by nutritional studies in which humans stricken with pellagra, a nicotinamide (niacine) deficiency disease, recovered after the addition of tryptophan or niacin to their diets (Krehl et al). Other studies established tryptophan as a precursor of NAD in many animal and plant systems (Foster et al). This pathway is closely related to the catabolic pathway of tryptophan (tryptophan degradation I (via anthranilate)), suggesting an evolutionary link between the two.

Though rare, the synthesis of NAD from tryptophan in prokaryotes has been observed in several organisms. Wilson and Henderson reported that Xanthomonas arboricola pv. pruni requires niacin for growth and can use tryptophan or 3-hydroxyanthranilic acid as a substitute [Wilson63]. Some members of the Actinomycete group were also reported to utilize tryptophan for NAD biosynthesis (Lingens et al).

Recent studies based on comparative genome analysis have identified the five genes involved in the "eukaryotic" pathway in several bacterial strains, confirming that some bacteria may indeed utilize this pathway rather than the aspartate pathway (Kurnasov et al).

In yeast, the de novo pathway consists of six enzymatic steps (catalyzed by the products of the BNA genes) and one non-enzymatic reaction. After the last enzymatic reaction (catalyzed by Bna6p), the de novo pathway converges with the salvage pathway (Panozzo et al).

In plants:

In plants current evidence strongly supports the NAD biosynthetic route from L-aspartate (NAD biosynthesis I (from aspartate)). However, the finding of gene homologs encoding enzymes of the early steps in the kynurenine pathway (this pathway) in the genome sequence of rice (Oryza sativa) does not rule out this pathway in monocotyledones and remains to be further investigated (Katoh et al).

Adapted from BioCyc.

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108352view09:25, 11 December 2019L DupuisConnected unconnected lines
106715view13:15, 17 September 2019MaintBotHMDB identifier normalization
102307view21:04, 17 December 2018KhanspersModified description
102306view21:01, 17 December 2018Khanspersremoved GenMAPP comment
70025view01:53, 12 July 2013AlexanderPicoModified title
69051view17:55, 8 July 2013EgonwMarked 'pyrophosphate' with a CAS number as metabolite.
62867view10:33, 3 May 2013CizarModified description
62270view22:24, 26 April 2013AlexanderPicoOntology Term : 'NAD biosynthetic pathway' added !
62269view22:24, 26 April 2013AlexanderPicoModified categories
61951view07:29, 22 April 2013CizarGrouped metabolites and aligned them
61804view10:55, 19 April 2013CizarModified description
61794view09:50, 19 April 2013CizarNew pathway

External references


View all...
NameTypeDatabase referenceComment
2-Amino-3-carboxymuconic acid semialdehydeMetaboliteHMDB0001330 (HMDB)
3-Hydroxyanthranilic acidMetaboliteHMDB0001476 (HMDB)
AFMIDGeneProductENSG00000183077 (Ensembl)
Adenosine monophosphateMetaboliteHMDB0000045 (HMDB)
Adenosine triphosphateMetaboliteHMDB0000538 (HMDB)
Carbon dioxideMetaboliteHMDB0001967 (HMDB)
Formic acidMetaboliteHMDB0000142 (HMDB)
HAAOGeneProductENSG00000162882 (Ensembl)
Hydrogen IonMetaboliteHMDB0059597 (HMDB)
KMOGeneProductENSG00000117009 (Ensembl)
KYNUGeneProductENSG00000115919 (Ensembl)
L-3-HydroxykynurenineMetaboliteHMDB0011631 (HMDB)
L-AlanineMetaboliteHMDB0000161 (HMDB)
L-Glutamic acidMetaboliteHMDB0000148 (HMDB)
L-GlutamineMetaboliteHMDB0000641 (HMDB)
L-KynurenineMetaboliteHMDB0000684 (HMDB)
L-TryptophanMetaboliteHMDB0000929 (HMDB)
N'-FormylkynurenineMetaboliteHMDB0001200 (HMDB)
NADMetaboliteHMDB0000902 (HMDB)
NADPHMetaboliteHMDB0000221 (HMDB)
NADPMetaboliteHMDB0000217 (HMDB)
NADSYN1GeneProductENSG00000172890 (Ensembl)
NMNAT1GeneProductENSG00000173614 (Ensembl)
Nicotinic acid adenine dinucleotideMetaboliteHMDB0001179 (HMDB)
Nicotinic acid mononucleotideMetaboliteHMDB0001132 (HMDB)
OxygenMetaboliteHMDB0001377 (HMDB)
Phosphoribosyl pyrophosphateMetaboliteHMDB0000280 (HMDB)
PyrophosphateMetaboliteHMDB0000250 (HMDB)
QPRTGeneProductENSG00000103485 (Ensembl)
Quinolinic acidMetaboliteHMDB0000232 (HMDB)
TDO2GeneProductENSG00000151790 (Ensembl)
WaterMetaboliteHMDB0002111 (HMDB)
pyrophosphateMetabolite2466-09-3 (CAS)

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