NAD biosynthesis II from tryptophan (Homo sapiens)
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Description
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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Ontology Terms
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DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
2-Amino-3-carboxymuconic acid semialdehyde | Metabolite | HMDB0001330 (HMDB) ![]() | |
3-Hydroxyanthranilic acid | Metabolite | HMDB0001476 (HMDB) ![]() | |
AFMID | GeneProduct | ENSG00000183077 (Ensembl) ![]() | |
Adenosine monophosphate | Metabolite | HMDB0000045 (HMDB) ![]() | |
Adenosine triphosphate | Metabolite | HMDB0000538 (HMDB) ![]() | |
Carbon dioxide | Metabolite | HMDB0001967 (HMDB) ![]() | |
Formic acid | Metabolite | HMDB0000142 (HMDB) ![]() | |
HAAO | GeneProduct | ENSG00000162882 (Ensembl) ![]() | |
Hydrogen Ion | Metabolite | HMDB0059597 (HMDB) ![]() | |
KMO | GeneProduct | ENSG00000117009 (Ensembl) ![]() | |
KYNU | GeneProduct | ENSG00000115919 (Ensembl) ![]() | |
L-3-Hydroxykynurenine | Metabolite | HMDB0011631 (HMDB) ![]() | |
L-Alanine | Metabolite | HMDB0000161 (HMDB) ![]() | |
L-Glutamic acid | Metabolite | HMDB0000148 (HMDB) ![]() | |
L-Glutamine | Metabolite | HMDB0000641 (HMDB) ![]() | |
L-Kynurenine | Metabolite | HMDB0000684 (HMDB) ![]() | |
L-Tryptophan | Metabolite | HMDB0000929 (HMDB) ![]() | |
N'-Formylkynurenine | Metabolite | HMDB0001200 (HMDB) ![]() | |
NAD | Metabolite | HMDB0000902 (HMDB) ![]() | |
NADPH | Metabolite | HMDB0000221 (HMDB) ![]() | |
NADP | Metabolite | HMDB0000217 (HMDB) ![]() | |
NADSYN1 | GeneProduct | ENSG00000172890 (Ensembl) ![]() | |
NMNAT1 | GeneProduct | ENSG00000173614 (Ensembl) ![]() | |
Nicotinic acid adenine dinucleotide | Metabolite | HMDB0001179 (HMDB) ![]() | |
Nicotinic acid mononucleotide | Metabolite | HMDB0001132 (HMDB) ![]() | |
Oxygen | Metabolite | HMDB0001377 (HMDB) ![]() | |
Phosphoribosyl pyrophosphate | Metabolite | HMDB0000280 (HMDB) ![]() | |
Pyrophosphate | Metabolite | HMDB0000250 (HMDB) ![]() | |
QPRT | GeneProduct | ENSG00000103485 (Ensembl) ![]() | |
Quinolinic acid | Metabolite | HMDB0000232 (HMDB) ![]() | |
TDO2 | GeneProduct | ENSG00000151790 (Ensembl) ![]() | |
Water | Metabolite | HMDB0002111 (HMDB) ![]() | |
pyrophosphate | Metabolite | 2466-09-3 (CAS) ![]() |
Annotated Interactions
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