Wyns W, Schwaiger M, Huang S C, Buxton D B, Hansen H, Selin C, Keen R, Phelps M E, Schelbert H R
Division of Nuclear Medicine and Biophysics, UCLA School of Medicine 90024.
Circ Res. 1989 Dec;65(6):1787-97. doi: 10.1161/01.res.65.6.1787.
The effects of glucose and lactate infusion on palmitate oxidation were compared with the effect of 2-tetradecylglycidic acid (TDGA), an irreversible inhibitor of the carnitine acyltransferase I, in normoxic canine myocardium. The initial capillary transit retention fraction of [1-11C]palmitate and its fractional distribution between oxidation and esterification in myocardium were measured by the residue detection method after intracoronary tracer injection, as well as by effluent measurements of 11CO2, the end product of palmitate oxidation. TDGA reduced the initial capillary transit retention fraction (from 56 +/- 13% to 37 +/- 6%; p less than 0.001) and oxidation of palmitate (n = 19), as also evidenced by the decrease in the fraction of tracer released as 11CO2 from 28 +/- 5% to 6 +/- 3% (p less than 0.001). Infusion of carbohydrate (glucose or lactate; n = 6) reduced 11CO2 production from 30 +/- 7% to 7 +/- 4% (p less than 0.05) but did not alter the initial capillary transit retention fraction of tracer (59 +/- 5% vs. 56 +/- 10%; NS). The latter was due to increased esterification into neutral lipids (41 +/- 11% of injected palmitate after carbohydrate infusion versus 21 +/- 12% in control conditions), as measured from multiexponential curve fittings. When carbohydrates were given after inhibition of palmitate oxidation by TDGA (n = 7), the 11C tissue clearance kinetics were strikingly similar to those observed after carbohydrate infusion alone. Thus, enhanced metabolic trapping of [1-11C]palmitate in myocardium resulted in initial capillary transit retention fractions that were not different from control conditions (41 +/- 5% vs. 48 +/- 12%; NS) despite inhibition of oxidation. The results show that the intracellular metabolism of palmitate contributes to the control of its uptake by myocardium. The findings are consistent with inhibition of palmitate oxidation by carbohydrates occurring at the same site as TDGA.
在常氧犬心肌中，比较了葡萄糖和乳酸输注对棕榈酸氧化的影响与肉碱脂酰转移酶I不可逆抑制剂2-十四烷基甘油酸（TDGA）的影响。冠状动脉内注射示踪剂后，通过残留检测法以及棕榈酸氧化终产物11CO2的流出量测量，测定了[1-11C]棕榈酸的初始毛细血管通过保留分数及其在心肌中氧化与酯化之间的分布分数。TDGA降低了棕榈酸的初始毛细血管通过保留分数（从56±13%降至37±6%；p<0.001）和氧化（n=19），从示踪剂以11CO2形式释放的分数从28±5%降至6±3%（p<0.001）也证明了这一点。输注碳水化合物（葡萄糖或乳酸；n=6）使11CO2产生量从30±7%降至7±4%（p<0.05），但未改变示踪剂的初始毛细血管通过保留分数（59±5%对56±10%；无显著性差异）。后者是由于多指数曲线拟合测量显示，酯化到中性脂质中的量增加（碳水化合物输注后注入的棕榈酸的41±11%，而对照条件下为21±12%）。当在TDGA抑制棕榈酸氧化后给予碳水化合物时（n=7），11C组织清除动力学与单独输注碳水化合物后观察到的情况惊人地相似。因此，尽管氧化受到抑制，但心肌中[1-11C]棕榈酸代谢捕获的增强导致初始毛细血管通过保留分数与对照条件无异（41±5%对48±12%；无显著性差异）。结果表明，棕榈酸的细胞内代谢有助于控制心肌对其的摄取。这些发现与碳水化合物在与TDGA相同的位点抑制棕榈酸氧化一致。
