Jones Patricia M, Butt Yasmeen, Messmer Bette, Boriak Richard, Bennett Michael J
Department of Pathology, University of Texas Southwestern Medical Center, Dalls, TX 75235, USA.
Biochem Biophys Res Commun. 2006 Jul 21;346(1):193-7. doi: 10.1016/j.bbrc.2006.05.107. Epub 2006 May 26.
Although mitochondrial fatty acid beta-oxidation (FAO) is considered to be well understood, further elucidation of the pathway continues through evaluation of patients with FAO defects. The FAO pathway can be examined by measuring the 3-hydroxy-fatty acid (3-OHFA) intermediates. We present a unique finding in the study of this pathway: the addition of medium-chain fatty acids to the culture media of fibroblasts results in generation of 3-OHFAs which are two carbons longer than the precursor substrate. Cultured skin fibroblasts from normal and LCHAD-deficient individuals were grown in media supplemented with various chain-length fatty acids. The cell-free medium was analyzed for 3-OHFAs by stable-isotope dilution gas-chromatography/mass-spectrometry. Our finding suggests that a novel carbon chain-length elongation process precedes the oxidation of medium-chain fatty acids. This previously undescribed metabolic step may have important implications for the metabolism of medium-chain triglycerides, components in the dietary treatment of a number of disorders.
尽管线粒体脂肪酸β-氧化（FAO）被认为已被充分了解，但通过对FAO缺陷患者的评估，该途径仍在不断得到进一步阐明。FAO途径可以通过测量3-羟基脂肪酸（3-OHFA）中间体来检测。我们在该途径的研究中呈现了一个独特的发现：向成纤维细胞的培养基中添加中链脂肪酸会导致生成比前体底物长两个碳的3-OHFAs。来自正常个体和LCHAD缺陷个体的培养皮肤成纤维细胞在补充了各种链长脂肪酸的培养基中生长。通过稳定同位素稀释气相色谱/质谱法分析无细胞培养基中的3-OHFAs。我们的发现表明，在中链脂肪酸氧化之前存在一个新的碳链长度延长过程。这个以前未被描述的代谢步骤可能对中链甘油三酯的代谢具有重要意义，中链甘油三酯是多种疾病饮食治疗中的成分。
