Autor: |
L Lligona-Trulla, A Arduini, T A Aldaghlas, M Calvani, J K Kelleher |
Jazyk: |
angličtina |
Rok vydání: |
1997 |
Předmět: |
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Zdroj: |
Journal of Lipid Research, Vol 38, Iss 7, Pp 1454-1462 (1997) |
Druh dokumentu: |
article |
ISSN: |
0022-2275 |
DOI: |
10.1016/S0022-2275(20)37427-7 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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