Inhibition of camitine-acyl transferase I by oxfenicine studied in vivo with [11C]-labeled fatty acids

被引:9
作者
Angsten, G [1 ]
Valind, S
Takalo, R
Neu, H
Meurling, S
Långström, B
机构
[1] Univ Uppsala, Childrens Hosp, Dept Pediat, S-75185 Uppsala, Sweden
[2] Univ Uppsala, PET Ctr, S-75105 Uppsala, Sweden
[3] Univ Uppsala Hosp, Dept Clin Physiol, S-75185 Uppsala, Sweden
[4] Univ Uppsala, Dept Organ Chem, S-75124 Uppsala, Sweden
基金
日本科学技术振兴机构;
关键词
carnitine; myocardial metabolism; fatty acid oxidation; PET; oxfenicine;
D O I
10.1016/j.nucmedbio.2005.03.003
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
Methods: Anesthetized pigs were studied with [C-11]-labeled fatty acids (FAs) with carbon chain length ranging from 8 to 16 carbon atoms, during control conditions and during inhibition of carnitine-palmitoyl transferase I (CPT I) with oxfenicine. The myocardial uptake of [C-11]FAs from blood was measured together with the relative distribution of [C-11]-acyl-CoA between rapid mitochondrial oxidation and incorporation into slow turnover lipid pools in the heart. Results: During baseline conditions, the fractional oxidative utilization of palmitate was almost as high as that of carnitine-independent short-chain FAs, unless the carnitine shuttle was inhibited by high levels of lactate. Inhibition of CPT I almost completely blocked the oxidative pathway for palmitic acid and reduced the fractional oxidative utilization, while the rate of oxidative metabolism of acyl-CoA was unaffected. Conclusions: [C-11]-Labeled FAs allow rapid oxidation to be well separated from esterification into slow turnover lipid pools in the heart of anaesthetized pigs. The fractional oxidative utilization of [C-11]-palmitate serves well to characterize, in vivo, the carnitine-dependent transfer of long-chain FAs. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:495 / 503
页数:9
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