Bielefeld D R, Vary T C, Neely J R
J Mol Cell Cardiol. 1985 Jun;17(6):619-25. doi: 10.1016/s0022-2828(85)80030-4.
High concentrations of lactate and oxfenicine inhibit fatty acid oxidation in cardiac muscle. The site of this inhibition was investigated in isolated perfused rat hearts. In hearts perfused with glucose (11 mM) and [U-14 C]palmitate (1.0 mM), addition of 5 mM lactate caused a 38% reduction in 14CO2 production. Tissue levels of long-chain acyl carnitine decreased suggesting that inhibition occurred at either fatty acyl CoA synthetase or carnitine-acyl CoA transferase. Cytosolic levels of acyl-CoA are low compared with mitochondrial levels and changes in acyl-CoA within the cytosolic compartment cannot be estimated directly. Consequently, the rate of conversion of 14C-palmitate to neutral lipids was used as an indicator of cytosolic acyl CoA levels. Lactate caused a 100% increase in 14C-fatty acid conversion to triglycerides suggesting that cytosolic levels of acyl-CoA increased in association with decreased acyl-carnitine. This indicates that lactate inhibited FFA oxidation at the level of carnitine-acyl CoA transferase. Oxfenicine (2 mM) reduced fatty acid oxidation by 45%, decreased acyl-carnitine levels by 80%, and increased conversion of 14C-palmitate to neutral lipids by 44%, suggesting that oxfenicine also inhibits fatty acid oxidation at the level of carnitine-acyl CoA transferase. These data further indicate that carnitine-acyl CoA transferase is an important site of control in the pathway of fatty acid oxidation.
高浓度的乳酸和奥昔芬净可抑制心肌中的脂肪酸氧化。在离体灌注的大鼠心脏中研究了这种抑制作用的位点。在用葡萄糖（11 mM）和[U-14C]棕榈酸（1.0 mM）灌注的心脏中，添加5 mM乳酸会使14CO2生成量减少38%。长链酰基肉碱的组织水平降低，表明抑制作用发生在脂肪酸辅酶A合成酶或肉碱-酰基辅酶A转移酶水平。与线粒体水平相比，胞质中的酰基辅酶A水平较低，无法直接估计胞质区室中酰基辅酶A的变化。因此，14C-棕榈酸转化为中性脂质的速率被用作胞质酰基辅酶A水平的指标。乳酸使14C-脂肪酸转化为甘油三酯的量增加了100%，这表明随着酰基肉碱水平的降低，胞质中的酰基辅酶A水平升高。这表明乳酸在肉碱-酰基辅酶A转移酶水平抑制了游离脂肪酸氧化。奥昔芬净（2 mM）使脂肪酸氧化减少45%，酰基肉碱水平降低80%，并使14C-棕榈酸转化为中性脂质的量增加44%，这表明奥昔芬净也在肉碱-酰基辅酶A转移酶水平抑制脂肪酸氧化。这些数据进一步表明，肉碱-酰基辅酶A转移酶是脂肪酸氧化途径中的一个重要调控位点。
