NAD biosynthesis II (from tryptophan) (WP2485)

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 [http://biocyc.org/META/new-image?type=PATHWAY&object=NADSYN-PWY&detail-level=3&ENZORG=TAX-9606 BioCyc].
last edited

Authors

Cizar, AlexanderPico, Egonw, Khanspers, MaintBot, L Dupuis, and Eweitz

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: nicotinamide adenine dinucleotide biosynthetic pathway

Participants

Label Type Compact Identifier
QPRT GeneProduct ensembl:ENSG00000103485
Formic acid Metabolite hmdb:HMDB0000142
KYNU GeneProduct ensembl:ENSG00000115919
Oxygen Metabolite hmdb:HMDB0001377
Hydrogen Ion Metabolite hmdb:HMDB0059597
L-Alanine Metabolite hmdb:HMDB0000161
Nicotinic acidadenine dinucleotide Metabolite hmdb:HMDB0001179
AFMID GeneProduct ensembl:ENSG00000183077
2-Amino-3-carboxymuconicacid semialdehyde Metabolite hmdb:HMDB0001330
pyrophosphate Metabolite cas:2466-09-3
HAAO GeneProduct ensembl:ENSG00000162882
L-Glutamine Metabolite hmdb:HMDB0000641
Water Metabolite hmdb:HMDB0002111
Pyrophosphate Metabolite hmdb:HMDB0000250
NADPH Metabolite hmdb:HMDB0000221
Adenosinetriphosphate Metabolite hmdb:HMDB0000538
Phosphoribosylpyrophosphate Metabolite hmdb:HMDB0000280
KMO GeneProduct ensembl:ENSG00000117009
NADP Metabolite hmdb:HMDB0000217
L-Kynurenine Metabolite hmdb:HMDB0000684
NADSYN1 GeneProduct ensembl:ENSG00000172890
3-Hydroxyanthranilic acid Metabolite hmdb:HMDB0001476
TDO2 GeneProduct ensembl:ENSG00000151790
NAD Metabolite hmdb:HMDB0000902
Carbon dioxide Metabolite hmdb:HMDB0001967
L-Tryptophan Metabolite hmdb:HMDB0000929
Water Metabolite hmdb:HMDB0002111
NMNAT1 GeneProduct ensembl:ENSG00000173614
Quinolinic acid Metabolite hmdb:HMDB0000232
L-Glutamic acid Metabolite hmdb:HMDB0000148
Pyrophosphate Metabolite hmdb:HMDB0000250
Adenosinemonophosphate Metabolite hmdb:HMDB0000045
Water Metabolite hmdb:HMDB0002111
Nicotinic acidmononucleotide Metabolite hmdb:HMDB0001132
L-3-Hydroxykynurenine Metabolite hmdb:HMDB0011631
Hydrogen Ion Metabolite hmdb:HMDB0059597
Water Metabolite hmdb:HMDB0002111
Hydrogen Ion Metabolite hmdb:HMDB0059597
Hydrogen Ion Metabolite hmdb:HMDB0059597
Hydrogen Ion Metabolite hmdb:HMDB0059597
Hydrogen Ion Metabolite hmdb:HMDB0059597
Oxygen Metabolite hmdb:HMDB0001377
Hydrogen Ion Metabolite hmdb:HMDB0059597
Water Metabolite hmdb:HMDB0002111
Hydrogen Ion Metabolite hmdb:HMDB0059597
Hydrogen Ion Metabolite hmdb:HMDB0059597
Hydrogen Ion Metabolite hmdb:HMDB0059597
Oxygen Metabolite hmdb:HMDB0001377
Hydrogen Ion Metabolite hmdb:HMDB0059597
Hydrogen Ion Metabolite hmdb:HMDB0059597

References