Details of Metabolite

General Information of MET (ID: META00343)
Name NAD
Synonyms   Click to Show/Hide Synonyms of This Metabolite
Adenine dinucleotide, dihydronicotinamide; Adenine-nicotinamide dinucleotide; Codehydrogenase I; Coenzyme I; Cozymase I; DPN; Dihydronicotinamide adenine dinucleotide; Dinucleotide, dihydronicotinamide adenine; Dinucleotide, nicotinamide-adenine; Diphosphopyridine nucleotide; NAD; NAD+; NADH; NICOTINAMIDE-adenine-dinucleotide; Nadide; Nicotinamide adenine dinucleotide; Nicotinamide-adenine dinucleotide; Nucleotide, diphosphopyridine; Oxidized diphosphopyridine nucleotide; beta-Diphosphopyridine nucleotide; beta-NAD; beta-NAD+; beta-Nicotinamide adenine dinucleotide
Source Endogenous;Escherichia Coli Metabolite;Yeast Metabolite;Food;Cosmetic;Microbial
Structure Type   (5'->5')-dinucleotides  (Click to Show/Hide the Complete Structure Type Hierarchy)
Nucleosides, nucleotides, and analogues
(5'->5')-dinucleotides
PubChem CID
5892
HMDB ID
HMDB0000902
Formula
C21H27N7O14P2
Structure
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3D MOL 2D MOL
  Click to Show/Hide the Molecular/Functional Data (External Links/Property/Function) of This Metabolite
KEGG ID
C00003
DrugBank ID
DB14128
ChEBI ID
44215
FooDB ID
FDB022309
ChemSpider ID
5682
Physicochemical Properties Molecular Weight 663.4 Topological Polar Surface Area 321
XlogP -6 Complexity 1120
Heavy Atom Count 44 Rotatable Bond Count 11
Hydrogen Bond Donor Count 7 Hydrogen Bond Acceptor Count 18
Function
NAD (or nicotinamide adenine dinucleotide) is used extensively in glycolysis and the citric acid cycle of cellular respiration. The reducing potential stored in NADH can be either converted into ATP through the electron transport chain or used for anabolic metabolism. ATP "energy" is necessary for an organism to live. Green plants obtain ATP through photosynthesis, while other organisms obtain it via cellular respiration. NAD is a coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by a pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH) (Dorland, 27th ed).
Regulatory Network
Full List of Protein(s) Regulating This Metabolite
      Hydrolases (EC 3)
            GTPase KRas (KRAS) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Overexpression of KRAS
                      Induced Change NAD concentration: decrease (FC = 0.52)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Lung cancer [ICD-11: 2C25]
                      Details It is reported that overexpression of KRAS leads to the decrease of NAD levels compared with control group.
            Kynureninase (KYNU) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Mutation (c.468T-A, c.1045_1051delTTTAAGC) of KYNU
                      Induced Change NAD concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Hereditary methemoglobinemia [ICD-11: 3A92]
                      Details It is reported that mutation (c.468T-A, c.1045_1051delTTTAAGC) of KYNU leads to the decrease of NAD levels compared with control group.
            Leukotriene-C4 hydrolase (GGT1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Knockdown (siRNA) of GGT1
                      Induced Change NAD concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Renal cell carcinoma [ICD-11: 2C90]
                      Details It is reported that knockdown of GGT1 leads to the increase of NAD levels compared with control group.
            Sulfatase sulf-1 (SULF1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [4]
                      Introduced Variation Knockdown (shRNA) of SULF1
                      Induced Change NAD concentration: decrease (FC = 0.18 / 0.24)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Ovarian cancer [ICD-11: 2C73]
                      Details It is reported that knockdown of SULF1 leads to the decrease of NAD levels compared with control group.
      Mitochondrial carrier (MC)
            Oxoglutarate/malate carrier protein (SLC25A11) Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [5]
                      Introduced Variation Knockdown (siRNA) of SLC25A11
                      Induced Change NAD concentration: decrease (FC = 0.60)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Melanoma [ICD-11: 2C30]
                      Details It is reported that knockdown of SLC25A11 leads to the decrease of NAD levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [5]
                      Introduced Variation Knockdown (shRNA) of SLC25A11
                      Induced Change NAD concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Melanoma [ICD-11: 2C30]
                      Details It is reported that knockdown of SLC25A11 leads to the decrease of NAD levels compared with control group.
      Nitrogen permease regulator (NPR)
            Natriuretic peptide receptor B (NPR2) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [6]
                      Introduced Variation Deletion of NPR2
                      Induced Change NAD concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that deletion of NPR2 leads to the increase of NAD levels compared with control group.
      Oxidoreductases (EC 1)
            3-hydroxyanthranilate oxygenase (HAAO) Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Mutation (c.558G-A) of HAAO
                      Induced Change NAD concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Hereditary methemoglobinemia [ICD-11: 3A92]
                      Details It is reported that mutation (c.558G-A) of HAAO leads to the decrease of NAD levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Mutation (c.483dupT) of HAAO
                      Induced Change NAD concentration: decrease (FC= 0.33)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Hereditary methemoglobinemia [ICD-11: 3A92]
                      Details It is reported that mutation (c.483dupT) of HAAO leads to the decrease of NAD levels compared with control group.
      Pore-forming PNC peptide (PNC)
            Cellular tumor antigen p53 (TP53) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [7]
                      Introduced Variation Knockout of TP53
                      Induced Change NAD concentration: increase (Log2 FC=1.37)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colon cancer [ICD-11: 2B90]
                      Details It is reported that knockout of TP53 leads to the increase of NAD levels compared with control group.
      Transcription factor (TF)
            Forkhead box protein O1 (FOXO1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [8]
                      Introduced Variation Overexpression of Foxo1
                      Induced Change NAD concentration: decrease (FC = 0.80)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of Foxo1 leads to the decrease of NAD levels compared with control group.
      Transferases (EC 2)
            Pyridoxal kinase (PDXK) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [9]
                      Introduced Variation Knockout (CRISPR/Cas9 sgRNA) of PDXK
                      Induced Change NAD concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Acute myeloid leukaemia [ICD-11: 2A60]
                      Details It is reported that knockout of PDXK leads to the decrease of NAD levels compared with control group.
      Zinc finger protein (ZIN)
            Protein snail homolog 1 (SNAI1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [10]
                      Introduced Variation Knockdown (shRNA) of SNAI1
                      Induced Change NAD concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Breast cancer [ICD-11: 2C60]
                      Details It is reported that knockdown of Snai1 leads to the increase of NAD levels compared with control group.
References
1 Capturing the metabolomic diversity of KRAS mutants in non-small-cell lung cancer cells. Oncotarget. 2014 Jul 15;5(13):4722-31.
2 NAD Deficiency, Congenital Malformations, and Niacin Supplementation. N Engl J Med. 2017 Aug 10;377(6):544-552.
3 Impairment of gamma-glutamyl transferase 1 activity in the metabolic pathogenesis of chromophobe renal cell carcinoma. Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):E6274-E6282.
4 Erratum to: Loss of HSulf-1 promotes altered lipid metabolism in ovarian cancer. Cancer Metab. 2014 Nov 4;2:24.
5 Loss of SLC25A11 causes suppression of NSCLC and melanoma tumor formation. EBioMedicine. 2019 Feb;40:184-197.
6 Npr2 inhibits TORC1 to prevent inappropriate utilization of glutamine for biosynthesis of nitrogen-containing metabolites. Sci Signal. 2014 Dec 16;7(356):ra120.
7 Integrative omics analysis of p53-dependent regulation of metabolism. FEBS Lett. 2018 Feb;592(3):380-393.
8 Metabolomic analysis of C2C12 myoblasts induced by the transcription factor FOXO1. FEBS Lett. 2019 Jun;593(12):1303-1312.
9 Vitamin B6 Addiction in Acute Myeloid Leukemia. Cancer Cell. 2020 Jan 13;37(1):71-84.e7.
10 Snail reprograms glucose metabolism by repressing phosphofructokinase PFKP allowing cancer cell survival under metabolic stress. Nat Commun. 2017 Feb 8;8:14374.

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