Linked Life Data

8373168

Source:http://linkedlifedata.com/resource/pubmed/id/8373168

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1993-10-12
pubmed:abstractText
3-Hydroxy-5,5-dimethylhexanoic acid (HDH) is an analogue of carnitine which differs only in the substitution of a quaternary carbon atom for the quaternary ammonium nitrogen. Thus HDH is isosteric with carnitine but lacks the quaternary ammonium positive charge. Racemic HDH, each of its enantiomers, and the O-acetyl derivative (Ac-HDH) were evaluated as alternate substrates and inhibitors for several carnitine acyltransferases. HDH and Ac-HDH are not substrates for carnitine acetyltransferase (CAT) at concentrations up to 10 mM, suggesting that the positive quaternary ammonium charge on carnitine is essential for CAT catalysis. However, HDH competitively inhibits CAT (Ki = 8.3 mM), carnitine palmitoyltransferase-I (CPT-I) (Ki = 3.6 mM), and CPT-II (Ki = 2.8 mM). Ac-HDH is also a competitive inhibitor of CAT when assayed in the reverse direction (Ki = 4.1 mM). Similarly, R-(+)-HDH and S-(-)-HDH are not substrates for CAT, but they are stereoselective competitive inhibitors (Ki = 20.3 and 7.5 mM for the R and S enantiomers, respectively). Stereoselective inhibition by HDH is even more dramatic with CPT-I, since S-(-)-HDH inhibits CPT-I (Ki = 1.4 mM) but R-(+)-HDH has no effect in concentrations up to 5 mM. As with CAT, HDH is a stereoselective inhibitor of CPT-II, and the Ki values for S-(-)- and R-(+)-HDH are 2.2 and 6.7 mM, respectively. Since the observed Ki values are significantly larger than the Km for carnitine, the positive charge on carnitine must also be important, but not essential, for binding to the carnitine site on carnitine acyltransferases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0003-9861
pubmed:author
pubmed:issnType
Print
pubmed:volume
305
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
307-12
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Carnitine acyltransferase enzymic catalysis requires a positive charge on the carnitine cofactor.
pubmed:affiliation
Department of Chemistry, University of Alabama at Birmingham 35294.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S.