Showing metabocard for Pyrazinecarboxamide (MMDBc0033197)
Record Information
Version
1.0
Status
Detected and Quantified
Creation Date
2021-11-19 04:38:41 UTC
Update Date
2022-08-31 22:29:43 UTC
MiMeDB ID
MMDBc0033197
Metabolite Identification
Common Name
Pyrazinecarboxamide
Description
Pyrazinecarboxamide, also known as pyrazinamide, is only found in individuals that have used or taken this drug. It is a pyrazine that is used therapeutically as an antitubercular agent. Pyrazinecarboxamide is an important sterilizing prodrug that shortens tuberculosis (TB) therapy. However, the mechanism of action of pyrazinecarboxamide is poorly understood because of its unusual properties. In literature it has been written that the pyrazinoic acid (POA), the active moiety of pyrazinecarboxamide, 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 pyrazinecarboxamide to POA, and the vitro susceptibility of a given strain of the organism appears to correspond to its pyrazinamidase activity. Experimental evidence suggests that pyrazinecarboxamide 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 pyrazinecarboxamide and its analogs inhibit the activity of purified FAS I.
Authors unspecified: 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. [PubMed:6109855 ]
Authors unspecified: 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. doi: 10.1016/0041-3879(83)90011-9. [PubMed:6356538 ]
Authors unspecified: 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. [PubMed:6386028 ]
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. doi: 10.1164/rccm.200206-626OC. Epub 2003 Jan 31. [PubMed:12569078 ]
