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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
1975-10-8
|
| pubmed:abstractText |
The cellular mycolate synthetase activity of Mycobacterium tuberculosis H37Ra was previously shown to be very sensitive to isoniazid (Wang, L., and K. Takayama. 1972. Antimicrob. Agents Chemother. 2: 438-441). We have now examined the question of how isoniazid inhibits the synthesis of mycolic acids. The saponifiable 14-C-labeled lipids of control and isoniazid-treated cells (1.0 mug/ml, 60 min) were compared on a Sephadex LH-20 column, and it appeared that the synthesis of the intermediate-sized fatty acids was partially inhibited. These fatty acids were fractionated as their methyl esters by Sephadex LH-20 column chromatograp-y and gas-liquid (6% Dexsil) chromatography. Mass sectral analysis of the fractionated lipids revealed several series of fatty acids: fraction II, C39-C56; fraction III, C27-C40. The long-chain fatty acids in three kinds of isoniazid-treated cells were examined: (a) long-term exposure (48 hr, 0.5 mug/ml), (b) short-term exposure (60 min, 1.0 mug/ml), and (c) variable exposure at low concentration (0-90 min, 0.2 mug/ml). Both long- and short-term exposure experiments showed that isoniazid inhibited the synthesis of saturated fatty acids greater than C26 and of unsaturated fatty acids greater than C24. The variable-exposure experiment at low isoniazid concentration showed that the syntheses of mycolic acids and long-chain fatty acid fractions II and III were inhibited to the same extent. These fatty acids may thus be precursors of mycolic acids.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0022-2275
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
16
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
308-17
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:806645-Acetates,
pubmed-meshheading:806645-Chromatography, Gas,
pubmed-meshheading:806645-Chromatography, Gel,
pubmed-meshheading:806645-Fatty Acids,
pubmed-meshheading:806645-Isoniazid,
pubmed-meshheading:806645-Molecular Weight,
pubmed-meshheading:806645-Mycobacterium tuberculosis,
pubmed-meshheading:806645-Mycolic Acids,
pubmed-meshheading:806645-Structure-Activity Relationship,
pubmed-meshheading:806645-Temperature,
pubmed-meshheading:806645-Time Factors
|
| pubmed:year |
1975
|
| pubmed:articleTitle |
Site of inhibitory action of isoniazid in the synthesis of mycolic acids in Mycobacterium tuberculosis.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|