General Information of MET (ID: META00658)
Name Isoniazid
Synonyms   Click to Show/Hide Synonyms of This Metabolite
4-Pyridinecarbohydrazide; Acid vanillylidenehydrazide, isonicotinic; Ftivazide; HIA; Hydrazid; Hydrazide; Hydrazide, isonicotinic acid; INH; Isohydrazide; Isonex; Isoniazid; Isonicotinate hydrazide; Isonicotinhydrazid; Isonicotinic acid hydrazide; Isonicotinic acid vanillylidenehydrazide; Isonicotinic hydrazide; Isonicotinohydrazide; Isonicotinoyl hydrazide; Isonicotinoylhydrazide; Isonicotinsaeurehydrazid; Isonicotinyl hydrazide; Isonicotinyl hydrazine; Isonicotinylhydrazine; Laniazid; Phthivazid; Phthivazide; Pyridine-4-carboxylate hydrazide; Pyridine-4-carboxylic acid hydrazide; Tubazide; Vanillylidenehydrazide, isonicotinic acid
Source Aromatic heteromonocyclic compounds
Structure Type   Pyridinecarboxylic acids and derivatives  (Click to Show/Hide the Complete Structure Type Hierarchy)
Organoheterocyclic compounds
Pyridines and derivatives
Pyridinecarboxylic acids and derivatives
PubChem CID
3767
HMDB ID
HMDB0015086
Formula
C6H7N3O
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
C07054
DrugBank ID
DB00951
ChEBI ID
6030
FooDB ID
FDB029229
ChemSpider ID
3635
Physicochemical Properties Molecular Weight 137.14 Topological Polar Surface Area 68
XlogP -0.7 Complexity 120
Heavy Atom Count 10 Rotatable Bond Count 1
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 3
Function
Isoniazid is only found in individuals that have used or taken this drug. It is an antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. Isoniazid is a prodrug and must be activated by bacterial catalase. Specficially, activation is associated with reduction of the mycobacterial ferric KatG catalase-peroxidase by hydrazine and reaction with oxygen to form an oxyferrous enzyme complex. Once activated, isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular <i>Mycobacterium tuberculosis</i> organisms. Specifically isoniazid inhibits InhA, the enoyl reductase from <i>Mycobacterium tuberculosis</i>, by forming a covalent adduct with the NAD cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive inhibitor of InhA.
Regulatory Network
Full List of Protein(s) Regulating This Metabolite
      Transferases (EC 2)
            Arylamine N-acetyltransferase 1 (NAT1) 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 [1]
                      Introduced Variation Knockout of Nat1
                      Induced Change Isoniazid concentration: increase (FC = 1.86)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual ...
                      Details It is reported that knockout of NAT leads to the increase of isoniazid levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Knockout of Nat1
                      Induced Change Isoniazid concentration: increase (FC = 2.00)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual ...
                      Details It is reported that knockout of NAT leads to the increase of isoniazid levels compared with control group.
            Arylamine N-acetyltransferase 2 (NAT2) 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 [1]
                      Introduced Variation Knockout of Nat2
                      Induced Change Isoniazid concentration: increase (FC = 1.86)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual ...
                      Details It is reported that knockout of NAT leads to the increase of isoniazid levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Knockout of Nat2
                      Induced Change Isoniazid concentration: increase (FC = 2.00)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual ...
                      Details It is reported that knockout of NAT leads to the increase of isoniazid levels compared with control group.
References
1 Deficiency of N-acetyltransferase increases the interactions of isoniazid with endobiotics in mouse liver. Biochem Pharmacol. 2017 Dec 1;145:218-225.

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