Linked Life Data

9949810

Source:http://linkedlifedata.com/resource/pubmed/id/9949810

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1999-3-2
pubmed:abstractText
Isoniazid is the most widely used antituberculosis drug. Genetic studies in Mycobacterium smegmatis identified the inhA-encoded, NADH-dependent enoyl acyl carrier protein reductase as the primary target for this drug. A reactive form of isoniazid inhibits InhA by reacting with the NAD(H) cofactor bound to the enzyme active site forming a covalent adduct (isonicotinic acyl NADH) that is apt to bind with high affinity. Resistance can occur by increased expression of InhA or by mutations that lower the enzyme's affinity to NADH. Both of these resistance mechanisms are observed in 30% of clinical tuberculosis isolates. Mutation in katG, which encodes catalase peroxidase, is the most common source for resistance. Another mechanism for isoniazid resistance, in M. smegmatis, occurs by defects in NADH dehydrogenase (Ndh) of the respiratory chain. Genetic data indicated that ndh mutations confer resistance by lowering the rate of NADH oxidation and increasing the intracellular NADH/NAD+ ratio. An increased amount of NADH may prevent formation of isonicotinic acyl NADH or may promote displacement of the isonicotinic acyl NADH from InhA. While our studies have identified this mechanism in M. smegmatis, results reported in early literature lead us to believe that it can occur in Mycobacterium tuberculosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1528-2511
pubmed:author
pubmed:issnType
Print
pubmed:volume
217
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
209-20; discussion 220-1
pubmed:dateRevised
2007-12-20
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Mechanisms for isoniazid action and resistance.
pubmed:affiliation
Department of Microbiology and Immunology, Howard Hughes Medical Institute, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review