L-Palmitoylcarnitine is an important endogenous fatty acid metabolite that simultaneously enhanced the ATP sensitivity of the ion channel with IC50 value fell from 62.0 ± 2.7 to 30.3 ±5.5µM[1]. L-Palmitoylcarnitine is a critical regulator in fatty acids metabolism, especially in mitochondrial fatty acid β-oxidation[2]. L-Palmitoylcarnitine weakly inhibits pyruvate-supported respiration in mitochondria but does not affect pyruvate utilization. It has stronger inhibitory effect on acetylcarnitine oxidation[3].
In vitro, L-Palmitoylcarnitine (1–10μM) incubated guinea-pig ventricular myocytes at 35°C for 10min largely inhibited the outward current transient associated with Na/K pump current[4]. L-Palmitoylcarnitine (10nM to10μM) incubated isolated guinea-pig ventricular myocytes for 40min produced concentration- and time-dependent changes of resting potential (RP) and action potential duration at 50% repolarization (APD50)[5].
In vivo, L-Palmitoylcarnitine (0, 0.25, 1, 4mg/kg) administrated into FeCl3-induced mouse thrombosis model and transient middle cerebral artery occlusion (tMCAO) mouse models via tail vein injections significantly inhibited FeCl3-induced arterial thrombosis, and also mitigated intracerebral thrombosis and inflammation in a transient middle cerebral artery occlusion (tMCAO) mouse model[6].
References:
[1] Haruna T, Horie M,Takano M,et al. Alteration of the membrane lipid environment by L-palmitoylcarnitine modulates K(ATP) channels in guinea-pig ventricular myocytes. Pflugers Arch. 2000;441(2-3):200-207.
[2] Liu Q Y, Li P W, Ma J L, et al. Arsenic exposure at environmentally relevant levels induced metabolic toxicity in development mice: Mechanistic insights from integrated transcriptome and metabolome. Environ Int. 2024 Aug:190:108819.
[3] Hutson S M, van Dop C, Lardy H A. Metabolism of pyruvate and carnitine esters in bovine epididymal sperm mitochondria. Arch Biochem Biophys. 1977 May;181(1):345-52.
[4] Tanaka M, Gilbert J, Pappano A J. Inhibition of sodium pump by l-palmitoylcarnitine in single guinea-pig ventricular myocytes. J Mol Cell Cardiol. 1992 Jul;24(7):711-9.
[5] Mészàros J, Pappano A J. Electrophysiological effects of L-palmitoylcarnitine in single ventricular myocytes. Am J Physiol. 1990 Apr;258(4 Pt 2):H931-8.
[6] Yang J, Cha L, Wang Y P, et al. L-Palmitoylcarnitine potentiates plasmin and tPA to inhibit thrombosis. Nat Prod Bioprospect. 2023 Nov 8;13(1):48.
L-Palmitoylcarnitine 是一种重要的内源性脂肪酸代谢物，可同时提高离子通道对 ATP 的敏感性，IC50 值在 30.3 ± 5.5µM和62.0 ± 2.7之间[1]。L-Palmitoylcarnitine 是脂肪酸代谢，尤其是线粒体脂肪酸 β-氧化的关键调控因子[2]。L-Palmitoylcarnitine 对丙酮酸支持的线粒体呼吸仅呈弱抑制，但不影响丙酮酸本身的利用，而对乙酰肉碱氧化的抑制作用更强[3]。
在体外实验中，L-Palmitoylcarnitine (1–10μM) 于35°C孵育豚鼠心室肌细胞10min，几乎完全抑制Na/K泵电流相关的外向瞬时电流[4]。L-Palmitoylcarnitine (10nM至10μM) 孵育离体豚鼠心室肌细胞40min，呈浓度-和时间依赖性改变静息电位及50%复极动作电位时程 (APD50)[5]。
在体内实验中，L-Palmitoylcarnitine (0、0.25、1、4mg/kg) 经尾静脉注射给予FeCl3诱导的小鼠血栓模型及短暂大脑中动脉阻塞 (tMCAO) 小鼠模型，显著抑制FeCl3诱导的动脉血栓形成，并在tMCAO模型中减轻脑内血栓与炎症[6]。