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Record Information
Version3.6
Creation Date2012-09-06 15:16:49 UTC
Update Date2016-02-11 01:28:41 UTC
HMDB IDHMDB14483
Secondary Accession NumbersNone
Metabolite Identification
Common NamePyrazinamide
DescriptionPyrazinamide is only found in individuals that have used or taken this drug. It is a pyrazine that is used therapeutically as an antitubercular agent.Pyrazinamide is an important sterilizing prodrug that shortens tuberculosis (TB) therapy. However, the mechanism of action of pyrazinamide is poorly understood because of its unusual properties. In literature it has been written that the pyrazinoic acid (POA), the active moiety of pyrazinamide, disrupted membrane energetics and inhibited membrane transport function at acid pH in Mycobacterium tuberculosis. The antimycobacterial activity appears to partly depend on conversion of the drug to POA. Susceptible strains of M. tuberculosis produce pyrazinamidase, an enzyme that deaminates pyrazinamide to POA, and the vitro susceptibility of a given strain of the organism appears to correspond to its pyrazinamidase activity. Experimental evidence suggests that pyrazinamide diffuses into M. tuberculosis in a passive manner, is converted into POA by pyrazinamidase, and because of an inefficient efflux system, accumulates in huge amounts in the bacterial cytoplasm. The accumulation of POA lowers the intracellular pH to a suboptimal level that is likely to inactivate a vital target enzyme such as fatty acid synthase. Recent studies (2007) demonstrated that pyrazinamide and its analogs inhibit the activity of purified FAS I.
Structure
Thumb
Synonyms
ValueSource
2-CarbamylpyrazineChEBI
2-PyrazinecarboxamideChEBI
PyrazinamidaChEBI
PyrazinamidumChEBI
Pyrazine carboxamideChEBI
PYRAZINE-2-carboxamideChEBI
PyrazineamideChEBI
Pyrazinoic acid amideChEBI
Pyrazinoate amideGenerator
PirazimidaHMDB
PirazinamidHMDB
PyrazinamdieHMDB
Pyrazine carboxylamideHMDB
PyrazinecarboxamideHMDB
Pyrazinecarboxylic acid amideHMDB
PZAHMDB
Chemical FormulaC5H5N3O
Average Molecular Weight123.1127
Monoisotopic Molecular Weight123.043261797
IUPAC Namepyrazine-2-carboxamide
Traditional Namepyrazinamide
CAS Registry Number98-96-4
SMILES
NC(=O)C1=NC=CN=C1
InChI Identifier
InChI=1S/C5H5N3O/c6-5(9)4-3-7-1-2-8-4/h1-3H,(H2,6,9)
InChI KeyInChIKey=IPEHBUMCGVEMRF-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as pyrazinecarboxamides. These are compounds containing a pyrazine ring which bears a carboxamide.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazines
Sub ClassPyrazines
Direct ParentPyrazinecarboxamides
Alternative Parents
Substituents
  • Pyrazinecarboxamide
  • Heteroaromatic compound
  • Primary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Antitubercular Agents
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point192 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility9.37e+01 g/LNot Available
LogP-1Not Available
Predicted Properties
PropertyValueSource
Water Solubility93.7 mg/mLALOGPS
logP-0.71ALOGPS
logP-1.2ChemAxon
logS-0.12ALOGPS
pKa (Strongest Acidic)13.06ChemAxon
pKa (Strongest Basic)-0.68ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area68.87 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity30.45 m3·mol-1ChemAxon
Polarizability11.13 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00339
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00339
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00339
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID1017
KEGG Compound IDC01956
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkPyrazinamide
NuGOwiki LinkHMDB14483
Metagene LinkHMDB14483
METLIN IDNot Available
PubChem Compound1046
PDB IDPZA
ChEBI ID45285
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Controlled trial of four thrice-weekly regimens and a daily regimen all given for 6 months for pulmonary tuberculosis. Lancet. 1981 Jan 24;1(8213):171-4. [6109855 ]
  2. Controlled clinical trial of 4 short-couse regimens of chemotherapy (three 6-month and one 8-month) for pulmonary tuberculosis. Tubercle. 1983 Sep;64(3):153-66. [6356538 ]
  3. A controlled trial of 6 months' chemotherapy in pulmonary tuberculosis. Final report: results during the 36 months after the end of chemotherapy and beyond. British Thoracic Society. Br J Dis Chest. 1984 Oct;78(4):330-6. [6386028 ]
  4. Yee D, Valiquette C, Pelletier M, Parisien I, Rocher I, Menzies D: Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. Am J Respir Crit Care Med. 2003 Jun 1;167(11):1472-7. Epub 2003 Jan 31. [12569078 ]

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
Not Available
Gene Name:
AOX1
Uniprot ID:
Q06278
Molecular weight:
147916.735
References
  1. Moriwaki Y, Yamamoto T, Nasako Y, Takahashi S, Suda M, Hiroishi K, Hada T, Higashino K: In vitro oxidation of pyrazinamide and allopurinol by rat liver aldehyde oxidase. Biochem Pharmacol. 1993 Sep 14;46(6):975-81. [8216357 ]
General function:
Involved in oxidoreductase activity
Specific function:
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro).
Gene Name:
XDH
Uniprot ID:
P47989
Molecular weight:
146422.99
References
  1. Moriwaki Y, Yamamoto T, Nasako Y, Takahashi S, Suda M, Hiroishi K, Hada T, Higashino K: In vitro oxidation of pyrazinamide and allopurinol by rat liver aldehyde oxidase. Biochem Pharmacol. 1993 Sep 14;46(6):975-81. [8216357 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]