Active-site probes of carnitine acyltransferases. Inhibition of carnitine acetyltransferase by hemiacetylcarnitinium, a reaction intermediate analogue

RD Gandour, WJ Colucci, TC Stelly, PS Brady… - Biochemical and …, 1986 - Elsevier
RD Gandour, WJ Colucci, TC Stelly, PS Brady, LJ Brady
Biochemical and biophysical research communications, 1986Elsevier
Summary Hemiacetylcarnitinium ((2S, 6R: 2R, 6S)-6-carboxymethyl-2-hydroxy-2, 4, 4-
trimethylmorpholinium) chloride is a relatively potent competitive inhibitor (Ki= 0.89 mM) of
pigeon breast carnitine acetyltransferase (CAT) and of the crude rat liver CAT (Ki= 4.72 mM)
but is neither an inhibitor nor an effective substrate for purified rat liver carnitine
palmitoyltransferase (CPT). It does not inhibit state 3 oxygen consumption in isolated hepatic
mitochondria using palmitioyl-CoA or palmitoylcarnitine as substrates. This compound is a …
Summary
Hemiacetylcarnitinium ((2S,6R:2R,6S)-6-carboxymethyl-2-hydroxy-2,4,4-trimethylmorpholinium) chloride is a relatively potent competitive inhibitor (Ki = 0.89 mM) of pigeon breast carnitine acetyltransferase (CAT) and of the crude rat liver CAT (Ki = 4.72 mM) but is neither an inhibitor nor an effective substrate for purified rat liver carnitine palmitoyltransferase (CPT). It does not inhibit state 3 oxygen consumption in isolated hepatic mitochondria using palmitioyl-CoA or palmitoylcarnitine as substrates. This compound is a reaction intermediate analogue of the proposed tetrahedral intermediate for acetyl transfer between acetylcarnitine and CoASH. Because the hemiketal carbon is chiral, a suggestion is made that one of the enantiomers has the same relative configuration as the proposed tetrahedral intermediate.
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