Nicotinic acid mononucleotide (BioDeep_00000003532)

 

Secondary id: BioDeep_00001869110

natural product human metabolite PANOMIX_OTCML-2023 Endogenous


代谢物信息卡片


3-carboxy-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(phosphonooxy)methyl]oxolan-2-yl]-1lambda5-pyridin-1-ylium

化学式: [C11H15NO9P]+ (336.048441)
中文名称: 烟酰胺单核苷酸
谱图信息: 最多检出来源 Homo sapiens(natural_products) 0.78%

Reviewed

Last reviewed on 2024-06-29.

Cite this Page

Nicotinic acid mononucleotide. BioDeep Database v3. PANOMIX ltd, a top metabolomics service provider from China. https://query.biodeep.cn/s/nicotinic_acid_mononucleotide (retrieved 2024-11-21) (BioDeep RN: BioDeep_00000003532). Licensed under the Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0).

分子结构信息

SMILES: C1=CC(=C[N+](=C1)C2C(C(C(O2)COP(=O)(O)O)O)O)C(=O)O
InChI: InChI=1S/C11H14NO9P/c13-8-7(5-20-22(17,18)19)21-10(9(8)14)12-3-1-2-6(4-12)11(15)16/h1-4,7-10,13-14H,5H2,(H2-,15,16,17,18,19)/p+1/t7-,8-,9-,10-/m1/s1

描述信息

Nicotinic acid mononucleotide, also known as nicotinate ribonucleotide, belongs to the class of organic compounds known as nicotinic acid nucleotides. These are pyridine nucleotides in which the pyridine base is nicotinic acid or a derivative thereof. Nicotinic acid mononucleotide is an extremely weak basic (essentially neutral) compound (based on its pKa). Nicotinic acid mononucleotide an intermediate in the cofactor biosynthesis and the nicotinate and nicotinamide metabolism pathways. It is a substrate for nicotinamide riboside kinase, ectonucleotide pyrophosphatase/phosphodiesterase, nicotinamide mononucleotide adenylyltransferase, 5-nucleotidase, nicotinate-nucleotide pyrophosphorylase, and 5(3)-deoxyribonucleotidase.

Nicotinic acid mononucleotide is an intermediate in the metabolism of Nicotinate and nicotinamide. It is a substrate for Ectonucleotide pyrophosphatase/phosphodiesterase 2, Ectonucleotide pyrophosphatase/phosphodiesterase 1, Nicotinamide mononucleotide adenylyltransferase 3, Cytosolic 5-nucleotidase IA, Cytosolic 5-nucleotidase IB, Nicotinate-nucleotide pyrophosphorylase, 5(3)-deoxyribonucleotidase (cytosolic type), Cytosolic purine 5-nucleotidase, Nicotinamide mononucleotide adenylyltransferase 2, Ectonucleotide pyrophosphatase/phosphodiesterase 3, 5-nucleotidase, 5(3)-deoxyribonucleotidase (mitochondrial) and Nicotinamide mononucleotide adenylyltransferase 1. [HMDB]

NaMN is the most common mononucleotide intermediate (a hub) in NAD biogenesis. For example, in E. coli all three pyridine precursors are converted into NaMN (Table 1 and Figure 3(a)). Qa produced by the de novo Asp–DHAP pathway (genes nadB and nadA) is converted into NaMN by QAPRT (gene nadC). Salvage of both forms of niacin proceeds via NAPRT (gene pncB) either directly upon or after deamidation by NMDSE (gene pncA). Overall, more than 90\% of approximately 680 analyzed bacterial genomes contain at least one of the pathways leading to the formation of NaMN. Most of them (∼480 genomes) have the entire set of nadBAC genes for NaMN de novo synthesis from Asp that are often clustered on the chromosome and/or are co-regulated by the same transcription factors (see Section 7.08.3.1.2). Among the examples provided in Table 1, F. tularensis (Figure 4(c)) has all three genes of this de novo pathway forming a single operon-like cluster and supporting the growth of this organism in the absence of any pyridine precursors in the medium. More than half the genomes with the Asp–DHAP pathway also contain a deamidating niacin salvage pathway (genes pncAB) as do many representatives of the α-, β-, and γ-Proteobacteria, Actinobacteria, and Bacillus/Clostridium group. As already emphasized, the genomic reconstruction approach provides an assessment of the metabolic potential of an organism, which may or may not be realized under given conditions. For example, E. coli and B. subtilis can utilize both de novo and PncAB Nm salvage pathways under the same growth conditions, whereas in M. tuberculosis (having the same gene pattern) the latter pathway was considered nonfunctional, so that the entire NAD pool is generated by the de novo NadABC route. However, a recent study demonstrated the functional activity of the Nm salvage pathway in vivo, under hypoxic conditions in infected macrophages.221 This study also implicated the two downstream enzymes of NAD synthesis (NAMNAT and NADSYN) as attractive chemotherapeutic targets to treat acute and latent forms of tuberculosis.

In approximately 100 species, including many Cyanobacteria (e.g., Synechococcus spp.), Bacteroidetes (e.g., Chlorobium spp.) and Proteobacteria (e.g., Caulobacter crescentus, Zymomonas mobilis, Desulfovibrio spp., and Shewanella spp. representing α-, β-, δ-, and γ-groups, respectively) the Asp–DHAP pathway is the only route to NAD biogenesis. Among them, nearly all Helicobacter spp. (except H. hepaticus), contain only the two genes nadA and nadC but lack the first gene of the pathway (nadB), which is a likely subject of nonorthologous gene replacement. One case of NadB (ASPOX) replacement by the ASPDH enzyme in T. maritima (and methanogenic archaea) was discussed in Section 7.08.2.1. However, no orthologues of the established ASPDH could be identified in Helicobacter spp. as well as in approximately 15 other diverse bacterial species that have the nadAC but lack the nadB gene (e.g., all analyzed Corynebacterium spp. except for C. diphtheriae). Therefore, the identity of the ASPOX or ASPDH enzyme in these species is still unknown, representing one of the few remaining cases of ‘locally missing genes’220 in the NAD subsystem. All other bacterial species contain either both the nadA and nadB genes (plus nadC) or none.

In a limited number of bacteria (∼20 species), mostly in the two distant groups of Xanthomonadales (within γ-Proteobacteria) and Flavobacteriales (within Bacteroidetes), the Asp–DHAP pathway of Qa synthesis is replaced by the Kyn pathway. As described in Section 7.08.2.1.2, four out of five enzymes (TRDOX, KYNOX, KYNSE, and HADOX) in the bacterial version of this pathway are close homologues of the respective eukaryotic enzymes, whereas the KYNFA gene is a subject of multiple nonorthologous replacements. Although the identity of one alternative form of KYNFA (gene kynB) was established in a group of bacteria that have a partial Kyn pathway for Trp degradation to anthranilate (e.g., in P. aeruginosa or B. cereus57), none of the known KYNFA homologues are present in Xanthomonadales or Flavobacteriales. In a few species (e.g., Salinispora spp.) a complete gene set of the Kyn pathway genes co-occurs with a complete Asp–DHAP pathway. Further experiments would be required to establish to what extent and under what conditions these two pathways contribute to Qa formation. As discussed, the QAPRT enzyme is shared by both de novo pathways, and a respective gene, nadC is always found in the genomes containing one or the other pathway. Similarly, gene nadC always co-occurs with Qa de novo biosynthetic genes with one notable exception of two groups of Streptococci, S. pneumonaie and S. pyogenes. Although all other members of the Lactobacillales group also lack the Qa de novo biosynthetic machinery and rely entirely on niacin salvage, only these two human pathogens contain a nadC gene. The functional significance of this ‘out of context’ gene is unknown, but it is tempting to speculate that it may be involved in a yet-unknown pathway of Qa salvage from the human host.

Among approximately 150 bacterial species that lack de novo biosynthesis genes and rely on deamidating salvage of niacin (via NAPRT), the majority (∼100) are from the group of Firmicutes. Such a functional variant (illustrated for Staphylococcus aureus in Figure 4(b)) is characteristic of many bacterial pathogens, both Gram-positive and Gram-negative (e.g., Brucella, Bordetella, and Campylobacter spp. from α-, β-, and δ-Proteobacteria, Borrelia, and Treponema spp. from Spirochaetes). Most of the genomes in this group contain both pncA and pncB genes that are often clustered on the chromosome and/or are co-regulated (see Section 7.08.3.1.2). In some cases (e.g., within Mollicutes and Spirochaetales), only the pncB, but not the pncA gene, can be reliably identified, suggesting that either of these species can utilize only the deamidated form of niacin (Na) or that some of them contain an alternative (yet-unknown) NMASE.

Although the nondeamidating conversion of Nm into NMN (via NMPRT) appears to be present in approximately 50 bacterial species (mostly in β- and γ-Proteobacteria), it is hardly ever the only route of NAD biogenesis in these organisms. The only possible exception is observed in Mycoplasma genitalium and M. pneumoniae that contain the nadV gene as the only component of pyridine mononucleotide biosynthetic machinery. In some species (e.g., in Synechocystes spp.), the NMPRT–NMNAT route is committed primarily to the recycling of endogenous Nm. On the other hand, in F. tularensis (Figure 4(c)), NMPRT (gene nadV) together with NMNAT (of the nadM family) constitute the functional nondeamidating Nm salvage pathway as it supports the growth of the nadE′-mutant on Nm but not on Na (L. Sorci et al., unpublished). A similar nondeamidating Nm salvage pathway implemented by NMPRT and NMNAT (of the nadR family) is present in some (but not all) species of Pasteurellaceae in addition to (but never instead of) the RNm salvage pathway (see below), as initially demonstrated for H. ducreyi.128

A two-step conversion of NaMN into NAD via a NaAD intermediate (Route I in Figure 2) is present in the overwhelming majority of bacteria. The signature enzyme of Route I, NAMNAT of the NadD family is present in nearly all approximately 650 bacterial species that are expected to generate NaMN via de novo or salvage pathways (as illustrated by Figures 3(a) and 3(b)). All these species, without a single exception, also contain NADSYN (encoded by either a short or a long form of the nadE gene), which is required for this route. The species that lack the NadD/NadE signature represent several relatively rare functional variants, including:

1.
Route I of NAD synthesis (NaMN → NaAD → NAD) variant via a bifunctional NAMNAT/NMNAT enzyme of the NadM family is common for archaea (see Section 7.08.3.2), but it appears to be present in only a handful of bacteria, such as Acinetobacter, Deinococcus, and Thermus groups. Another unusual feature of the latter two groups is the absence of the classical NADKIN, a likely subject of a nonorthologous replacement that remains to be elucidated.

2.
Route II of NAD synthesis (NaMN → NMN → NAD). This route is implemented by a combination of the NMNAT of either the NadM family (as in F. tularensis) or the NadR family (as in M. succinoproducens and A. succinogenes) with NMNSYN of the NadE′ family. The case of F. tularensis described in Section 7.08.2.4 is illustrated in Figure 3(b). The rest of the NAD biosynthetic machinery in both species from the Pasteurellaceae group, beyond the shared Route II, is remarkably different from that in F. tularensis. Instead of de novo biosynthesis, they harbor a Na salvage pathway via NAPRT encoded by a pncB gene that is present in a chromosomal cluster with nadE′. Neither of these two genes are present in other Pasteurellaceae that lack the pyridine carboxylate amidation machinery (see below).

3.
Salvage of RNm (RNm → NMN → NAD). A genomic signature of this pathway, a combination of the PnuC-like transporter and a bifunctional NMNAT/RNMKIN of the NadR family, is present in many Enterobacteriaceae and in several other diverse species (e.g., in M. tuberculosis). However, in H. influenzae (Figure 3(d)) and related members of Pasteurellaceae, it is the only route of NAD biogenesis. As shown in Table 1, H. influenzae as well as many other members of this group have lost nearly all components of the rich NAD biosynthetic machinery that are present in their close phylogenetic neighbors (such as E. coli and many other Enterobacteriaceae). This pathway is an ultimate route for utilization of the so called V-factors (NADP, NAD, NMN, or RNm) that are required to support growth of H. influenzae. It was established that all other V-factors are degraded to RNm by a combination of periplasmic- and membrane-associated hydrolytic enzymes.222 Although PnuC was initially considered an NMN transporter,223 its recent detailed analysis in both H. influenzae and Salmonella confirmed that its actual physiological function is in the uptake of RNm coupled with the phosphorylation of RNM to NMN by RNMKIN.17,148,224 As already mentioned, H. ducreyi and several other V-factor-independent members of the Pasteurellaceae group (H. somnus, Actinobacillus pleuropneumoniae, and Actinomycetemcomitans) harbor the NMNAT enzyme (NadV) that allows them to grow in the presence of Nm (but not Na) in the medium (Section 7.08.2.2).

4.
Uptake of the intact NAD. Several groups of phylogenetically distant intracellular endosymbionts with extremely truncated genomes contain only a single enzyme, NADKIN, from the entire subsystem. Among them are all analyzed species of the Wolbachia, Rickettsia, and Blochmannia groups. These species are expected to uptake and utilize the intact NAD from their host while retaining the ability to convert it into NADP. Among all analyzed bacteria, only the group of Chlamydia does not have NADKIN and depends on the salvage of both NAD and NADP via a unique uptake system.157

A comprehensive genomic reconstruction of the metabolic potential (gene annotations and asserted pathways) across approximately 680 diverse bacterial genomes sets the stage for the accurate cross-genome projection and prediction of regulatory mechanisms that control the realization of this potential in a variety of species and growth conditions. In the next section, we summarize the recent accomplishments in the genomic reconstruction of NAD-related regulons in bacteria.

Nicotinic acid mononucleotide. CAS Common Chemistry. CAS, a division of the American Chemical Society, n.d. https://commonchemistry.cas.org/detail?cas_rn=321-02-8 (retrieved 2024-06-29) (CAS RN: 321-02-8). Licensed under the Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0).

同义名列表

25 个代谢物同义名

3-carboxy-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(phosphonooxy)methyl]oxolan-2-yl]-1lambda5-pyridin-1-ylium; Nicotinic acid beta-D-ribonucleotide; beta-Nicotinic acid D-ribonucleotide; Deamido nicotinamide ribonucleotide; beta-Nicotinic acid mononucleotide; Nicotinic acid b-D-ribonucleotide; b-Nicotinic acid D-ribonucleotide; β-Nicotinic acid D-ribonucleotide; Nicotinic acid β-D-ribonucleotide; beta-Nicotinate D-ribonucleotide; β-Nicotinic acid mononucleotide; Nicotinic acid D-ribonucleotide; Nicotinic acid mono nucleotide; b-Nicotinate D-ribonucleotide; Nicotinate β-D-ribonucleotide; Nicotinate b-D-ribonucleotide; nicotinic acid mononucleotide; β-Nicotinate D-ribonucleotide; Nicotinic acid ribonucleotide; Nicotinate D-ribonucleotide; Nicotinate mononucleotide; Nicotinate ribonucleotide; Nicotinic mononucleotide; Nicotinic acid ribotide; Deamido-NMN



数据库引用编号

23 个数据库交叉引用编号

分类词条

相关代谢途径

Reactome(5)

BioCyc(4)

PlantCyc(0)

代谢反应

340 个相关的代谢反应过程信息。

Reactome(90)

BioCyc(11)

WikiPathways(3)

Plant Reactome(225)

INOH(2)

PlantCyc(0)

COVID-19 Disease Map(1)

PathBank(8)

  • Adenosylcobalamin Salvage from Cobinamide: Adenosine triphosphate + Cobinamide + Water ⟶ Adenosine diphosphate + Cobinamide + Hydrogen Ion + Phosphate
  • Adenosylcobalamin Salvage from Cobinamide: Adenosine triphosphate + Cyanocobalamin + Water ⟶ Adenosine diphosphate + Cyanocobalamin + Hydrogen Ion + Phosphate
  • NAD Biosynthesis: Adenosine triphosphate + L-Glutamine + Nicotinic acid adenine dinucleotide + Water ⟶ Adenosine monophosphate + Hydrogen Ion + L-Glutamic acid + NAD + Pyrophosphate
  • NAD Salvage: Adenosine triphosphate + L-Glutamine + Nicotinic acid adenine dinucleotide + Water ⟶ Adenosine monophosphate + Hydrogen Ion + L-Glutamic acid + NAD + Pyrophosphate
  • Nicotinate and Nicotinamide Metabolism: Adenosine triphosphate + L-Glutamine + Nicotinic acid adenine dinucleotide + Water ⟶ Adenosine monophosphate + L-Glutamic acid + NAD + Pyrophosphate
  • NAD Biosynthesis: Adenosine triphosphate + Ammonium + Nicotinic acid adenine dinucleotide ⟶ Adenosine monophosphate + Hydrogen Ion + NAD + Pyrophosphate
  • NAD Salvage: Adenosine triphosphate + L-Glutamine + Nicotinic acid adenine dinucleotide + Water ⟶ Adenosine monophosphate + Hydrogen Ion + L-Glutamic acid + NAD + Pyrophosphate
  • NAD Metabolism: N'-Formylkynurenine + Water ⟶ Formic acid + Hydrogen Ion + L-Kynurenine

PharmGKB(0)

1 个相关的物种来源信息

在这里通过桑基图来展示出与当前的这个代谢物在我们的BioDeep知识库中具有相关联信息的其他代谢物。在这里进行关联的信息来源主要有:

  • PubMed: 来源于PubMed文献库中的文献信息,我们通过自然语言数据挖掘得到的在同一篇文献中被同时提及的相关代谢物列表,这个列表按照代谢物同时出现的文献数量降序排序,取前10个代谢物作为相关研究中关联性很高的代谢物集合展示在桑基图中。
  • NCBI Taxonomy: 通过文献数据挖掘,得到的代谢物物种来源信息关联。这个关联信息同样按照出现的次数降序排序,取前10个代谢物作为高关联度的代谢物集合展示在桑吉图上。
  • Chemical Taxonomy: 在物质分类上处于同一个分类集合中的其他代谢物
  • Chemical Reaction: 在化学反应过程中,存在为当前代谢物相关联的生化反应过程中的反应底物或者反应产物的关联代谢物信息。

点击图上的相关代谢物的名称,可以跳转到相关代谢物的信息页面。



文献列表

  • Dahyun Hwang, HyunA Jo, Seong-Ho Ma, Young-Hee Lim. Oxyresveratrol stimulates mucin production in an NAD+-dependent manner in human intestinal goblet cells. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2018 Aug; 118(?):880-888. doi: 10.1016/j.fct.2018.06.039. [PMID: 29935245]
  • Federica Zamporlini, Silverio Ruggieri, Francesca Mazzola, Adolfo Amici, Giuseppe Orsomando, Nadia Raffaelli. Novel assay for simultaneous measurement of pyridine mononucleotides synthesizing activities allows dissection of the NAD(+) biosynthetic machinery in mammalian cells. The FEBS journal. 2014 Nov; 281(22):5104-19. doi: 10.1111/febs.13050. [PMID: 25223558]
  • Sathisha Upparahalli Venkateshaiah, Sharmin Khan, Wen Ling, Rakesh Bam, Xin Li, Frits van Rhee, Saad Usmani, Bart Barlogie, Joshua Epstein, Shmuel Yaccoby. NAMPT/PBEF1 enzymatic activity is indispensable for myeloma cell growth and osteoclast activity. Experimental hematology. 2013 Jun; 41(6):547-557.e2. doi: 10.1016/j.exphem.2013.02.008. [PMID: 23435312]
  • Hyung-Seop Youn, Mun-Kyoung Kim, Gil Bu Kang, Tae Gyun Kim, Jung-Gyu Lee, Jun Yop An, Kyoung Ryoung Park, Youngjin Lee, Jung Youn Kang, Hye-Eun Song, Inju Park, Chunghee Cho, Shin-Ichi Fukuoka, Soo Hyun Eom. Crystal structure of Sus scrofa quinolinate phosphoribosyltransferase in complex with nicotinate mononucleotide. PloS one. 2013; 8(4):e62027. doi: 10.1371/journal.pone.0062027. [PMID: 23626766]
  • Hyung-Seop Youn, Mun-Kyoung Kim, Gil Bu Kang, Tae Gyun Kim, Jun Yop An, Jung-Gyu Lee, Kyoung Ryoung Park, Youngjin Lee, Shin-Ichi Fukuoka, Soo Hyun Eom. Crystallization and preliminary X-ray crystallographic analysis of quinolinate phosphoribosyltransferase from porcine kidney in complex with nicotinate mononucleotide. Acta crystallographica. Section F, Structural biology and crystallization communications. 2012 Dec; 68(Pt 12):1488-90. doi: 10.1107/s1744309112040638. [PMID: 23192029]
  • Hiroshi Ashihara, Yuling Yin, Riko Katahira, Shin Watanabe, Tetsuro Mimura, Hamako Sasamoto. Comparison of the formation of nicotinic acid conjugates in leaves of different plant species. Plant physiology and biochemistry : PPB. 2012 Nov; 60(?):190-5. doi: 10.1016/j.plaphy.2012.08.007. [PMID: 22983143]
  • Shin-nosuke Hashida, Hideyuki Takahashi, Maki Kawai-Yamada, Hirofumi Uchimiya. Arabidopsis thaliana nicotinate/nicotinamide mononucleotide adenyltransferase (AtNMNAT) is required for pollen tube growth. The Plant journal : for cell and molecular biology. 2007 Feb; 49(4):694-703. doi: 10.1111/j.1365-313x.2006.02989.x. [PMID: 17270012]
  • Keri Wang, Kenneth Conn, George Lazarovits. Involvement of quinolinate phosphoribosyl transferase in promotion of potato growth by a Burkholderia strain. Applied and environmental microbiology. 2006 Jan; 72(1):760-8. doi: 10.1128/aem.72.1.760-768.2006. [PMID: 16391116]
  • Graham Noctor, Guillaume Queval, Bertrand Gakière. NAD(P) synthesis and pyridine nucleotide cycling in plants and their potential importance in stress conditions. Journal of experimental botany. 2006; 57(8):1603-20. doi: 10.1093/jxb/erj202. [PMID: 16714307]
  • K Shibata, T Fukuwatari, E Sugimoto. Reversed-phase high-performance liquid chromatography of nicotinic acid mononucleotide for measurement of quinolinate phosphoribosyltransferase. Journal of chromatography. B, Biomedical sciences and applications. 2000 Dec; 749(2):281-5. doi: 10.1016/s0378-4347(00)00406-0. [PMID: 11145065]
  • A C Foster, E Okuno, D S Brougher, R Schwarcz. A radioenzymatic assay for quinolinic acid. Analytical biochemistry. 1986 Oct; 158(1):98-103. doi: 10.1016/0003-2697(86)90595-6. [PMID: 2948416]
  • A C Foster, R Schwarcz. Characterization of quinolinic acid phosphoribosyltransferase in human blood and observations in Huntington's disease. Journal of neurochemistry. 1985 Jul; 45(1):199-205. doi: 10.1111/j.1471-4159.1985.tb05493.x. [PMID: 2582090]