NAD Biosynthesis II (from tryptophan) (Bos taurus)

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spontaneousCarbon dioxideL-Glutamic acidPyrophosphateTDO2N'-FormylkynurenineNADPPhosphoribosylpyrophosphateAdenosinetriphosphateQuinolinic acidAFMIDL-AlanineWaterAdenosinemonophosphateL-KynurenineNMNAT1NADPHAdenosinetriphosphate2-Amino-3-carboxymuconicacid semialdehydeL-3-HydroxykynureninePyrophosphateL-GlutamineHydrogen IonOxygenNicotinic acidadenine dinucleotideNicotinic acidmononucleotideNADSYN1Formic acidL-TryptophanWaterKYNUWaterQPRTNADHAAOKMOpyrophosphate3-Hydroxyanthranilic acidHydrogen 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 [Krehl45]. Other studies established tryptophan as a precursor of NAD in many animal and plant systems [Foster80a]. 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 [Lingens64].

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 [Kurnasov03].

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 [Panozzo02].

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 [Katoh06] [Katoh04].


GenMAPP notes
This pathway was inferred from Homo sapiens pathway WP2485(70025) with a 100.0% conversion rate.

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106000view11:52, 16 August 2019MaintBotHMDB identifier normalization
80832view15:27, 30 June 2015MkutmonNew pathway

External references


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NameTypeDatabase referenceComment
2-Amino-3-carboxymuconic acid semialdehydeMetaboliteHMDB01330 (HMDB)
3-Hydroxyanthranilic acidMetaboliteHMDB01476 (HMDB)
AFMIDGeneProductENSBTAG00000007125 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000183077
Adenosine monophosphateMetaboliteHMDB00045 (HMDB)
Adenosine triphosphateMetaboliteHMDB00538 (HMDB)
Carbon dioxideMetaboliteHMDB01967 (HMDB)
Formic acidMetaboliteHMDB00142 (HMDB)
HAAOGeneProductENSBTAG00000004674 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000162882
Hydrogen IonMetaboliteHMDB59597 (HMDB)
KMOGeneProductENSBTAG00000014439 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000117009
KYNUGeneProductENSBTAG00000032277 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000115919
L-3-HydroxykynurenineMetaboliteHMDB11631 (HMDB)
L-AlanineMetaboliteHMDB00161 (HMDB)
L-Glutamic acidMetaboliteHMDB00148 (HMDB)
L-GlutamineMetaboliteHMDB00641 (HMDB)
L-KynurenineMetaboliteHMDB00684 (HMDB)
L-TryptophanMetaboliteHMDB00929 (HMDB)
N'-FormylkynurenineMetaboliteHMDB01200 (HMDB)
NADMetaboliteHMDB00902 (HMDB)
NADPHMetaboliteHMDB00221 (HMDB)
NADPMetaboliteHMDB00217 (HMDB)
NADSYN1GeneProductENSBTAG00000016470 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000172890
NMNAT1GeneProductENSBTAG00000001361 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000173614
Nicotinic acid adenine dinucleotideMetaboliteHMDB01179 (HMDB)
Nicotinic acid mononucleotideMetaboliteHMDB01132 (HMDB)
OxygenMetaboliteHMDB01377 (HMDB)
Phosphoribosyl pyrophosphateMetaboliteHMDB00280 (HMDB)
PyrophosphateMetaboliteHMDB00250 (HMDB)
QPRTGeneProductENSBTAG00000018082 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000103485
Quinolinic acidMetaboliteHMDB00232 (HMDB)
TDO2GeneProductENSBTAG00000011062 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000151790
WaterMetaboliteHMDB02111 (HMDB)
pyrophosphateMetabolite2466-09-3 (CAS)

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