Lligona-Trulla L, Arduini A, Aldaghlas T A, Calvani M, Kelleher J K
Department of Research, Sigma Tau S.p.A., Pomezia, Italy.
J Lipid Res. 1997 Jul;38(7):1454-62.
Acetyl-L-carnitine is known as a reservoir of activated acetyl units and as a modulator of metabolic function. The objective of this study was to quantify the fate of the acetyl moiety of acetyl-L-carnitine in lipogenic pathways. Lipogenesis was studied in an adipocyte model, differentiated 3T3-L1 cells, and a hepatoma cell, HepG2 cells. Lipogenesis and ketogenesis were examined in rat hepatocytes. Both de novo synthesis and elongation of fatty acids were investigated using gas chromatography/mass spectrometry and [1,2-(13)C]acetyl-L-carnitine. Comparisons were performed with [13C]glucose and [13C]acetate. Isotopomer Spectral Analysis, a stable isotope method for differentiating between the enrichment of the precursor and the amount of synthesis was used to analyze the data. Acetyl-L-carnitine was generally less effective than acetate as a precursor for de novo lipogenesis. The effects of acetyl-L-carnitine were not identical to those of acetate plus carnitine as expected if acetyl-L-carnitine flux to acetyl CoA is controlled by carnitine acetyl transferase. Acetyl-L-carnitine (2 mM) contributed approximately 10% of the lipogenic acetyl-CoA used for synthesis and elongation as well as 6% of the ketogenic acetyl-CoA. No differences were found between the precursor enrichment for de novo lipogenesis and for elongation of saturated fatty acids. Flux of acetyl-L-carnitine to lipid was increased, not decreased, by the ATP citrate lyase inhibitor, -hydroxycitrate. In contrast, flux of glucose to lipid was dramatically decreased by this inhibitor. These results indicate that flux of acetyl-L-carnitine to lipid can bypass citrate and utilize cytosolic acetyl-CoA synthesis.
乙酰左旋肉碱被认为是活性乙酰单位的储存库和代谢功能的调节剂。本研究的目的是量化乙酰左旋肉碱的乙酰部分在脂肪生成途径中的去向。在脂肪细胞模型、分化的3T3-L1细胞和肝癌细胞HepG2细胞中研究了脂肪生成。在大鼠肝细胞中检测了脂肪生成和酮生成。使用气相色谱/质谱法和[1,2-(13)C]乙酰左旋肉碱研究了脂肪酸的从头合成和延长。与[13C]葡萄糖和[13C]乙酸盐进行了比较。采用同位素异构体光谱分析（一种用于区分前体富集和合成量的稳定同位素方法）来分析数据。作为从头脂肪生成的前体，乙酰左旋肉碱通常不如乙酸盐有效。如果乙酰左旋肉碱向乙酰辅酶A的通量受肉碱乙酰转移酶控制，那么乙酰左旋肉碱的作用与乙酸盐加肉碱的作用并不相同。乙酰左旋肉碱（2 mM）约占用于合成和延长的脂肪生成乙酰辅酶A的10%，以及生酮乙酰辅酶A的6%。从头脂肪生成和饱和脂肪酸延长的前体富集之间未发现差异。ATP柠檬酸裂解酶抑制剂羟基柠檬酸增加了乙酰左旋肉碱向脂质的通量，而非降低。相反，该抑制剂显著降低了葡萄糖向脂质的通量。这些结果表明，乙酰左旋肉碱向脂质的通量可以绕过柠檬酸并利用胞质乙酰辅酶A合成。
