Format

Send to

Choose Destination
J Med Chem. 1993 Jan 22;36(2):237-42.

(+)-Hemipalmitoylcarnitinium strongly inhibits carnitine palmitoyltransferase-I in intact mitochondria.

Author information

1
Department of Chemistry, Louisiana State University, Baton Rouge 70803-1804.

Abstract

The reaction of the methyl ester of (R)-norcarnitine with 1-bromo-2-heptadecanone produces (+)-6-[(methoxycarbonyl)methyl]-2-pentadecyl-4,4-dimethylmorpholinium bromide, 3, which hydrolyzes to (+)-6-(carboxylatomethyl)-2-pentadecyl-4,4-dimethylmorpholinium (hemipalmitoylcarnitinium, HPC) upon treatment with aqueous sodium hydroxide. Single-crystal X-ray analyses have confirmed the structures of (+)-HPC and 3. (+)-HPC inhibits carnitine palmitoyltransferase (CPT-I) activity for the forward reaction (palmitoyl-CoA + carnitine-->) in intact mitochondria from rat heart and rat liver. (+)-HPC competitively (versus carnitine) inhibits CPT-I activity in both rat heart and liver mitochondria with Ki = 2.8 +/- 0.5 and 4.2 +/- 0.7 microM, respectively. As one of the strongest specific inhibitors of CPT-I, HPC is a potential therapeutic agent in myocardial ischemia and Type II diabetes.

PMID:
8423595
DOI:
10.1021/jm00054a007
[Indexed for MEDLINE]

Supplemental Content

Loading ...
Support Center