Nakamura M T, Nara T Y
Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, 905 S. Goodwin Avenue, 61801, USA.
Biochem Soc Trans. 2002 Nov;30(Pt 6):1076-9. doi: 10.1042/bst0301076.
Stearoyl-CoA desaturase (SCD) catalyses the synthesis of oleic acid (18:1, n -9), which is mostly esterified into triacylglycerols (TAGs) as an energy reserve. Delta-6 Desaturase (D6D) and Delta-5 desaturase (D5D) are the key enzymes for the synthesis of highly unsaturated fatty acids (HUFAs), such as arachidonic acid (20:4, n -6) and docosahexaenoic acid (22:6, n -3), that are incorporated in phospholipids (PLs) and perform essential physiological functions. Despite these different physiological roles of SCD and D6D/D5D, these desaturases share common regulatory features, including dependence of expression on insulin, suppression by HUFAs, and induction by peroxisome proliferators (PPs). A key regulator of desaturase gene expression is sterol-regulatory element binding protein-1c (SREBP-1c), which mediates transcriptional activation of the SCD and D6D genes by insulin and inhibition by HUFAs. Because HUFAs are poorly incorporated into TAGs, the primary role of SREBP-1c in liver may be monitoring and regulating fatty acid composition in PLs rather than the regulation of TAG synthesis. The induction of desaturases by PPs is enigmatic because the major effect of PPs is induction of fatty acid oxidation enzymes by activating PP-activated receptor-alpha (PPARa). To our knowledge, no other gene that is induced by both SREBP-1 and PP has been identified. It is yet to be determined whether PPARa mediates the process directly. Available data suggest that the induction of desaturases by PPs may be a compensatory response to an increased demand for unsaturated fatty acids because PPs increase fatty acid degradation and induce proliferation of peroxisomes.
硬脂酰辅酶A去饱和酶（SCD）催化油酸（18:1，n -9）的合成，油酸大多作为能量储备酯化为三酰甘油（TAGs）。Δ-6去饱和酶（D6D）和Δ-5去饱和酶（D5D）是合成高度不饱和脂肪酸（HUFAs）的关键酶，如花生四烯酸（20:4，n -6）和二十二碳六烯酸（22:6，n -3），这些脂肪酸被整合到磷脂（PLs）中并发挥重要的生理功能。尽管SCD和D6D/D5D有这些不同的生理作用，但这些去饱和酶具有共同的调节特征，包括表达对胰岛素的依赖性、被HUFAs抑制以及被过氧化物酶体增殖物（PPs）诱导。去饱和酶基因表达的一个关键调节因子是固醇调节元件结合蛋白-1c（SREBP-1c），它介导胰岛素对SCD和D6D基因的转录激活以及HUFAs对其的抑制。由于HUFAs很难整合到TAGs中，SREBP-1c在肝脏中的主要作用可能是监测和调节PLs中的脂肪酸组成，而不是调节TAG合成。PPs对去饱和酶的诱导作用令人费解，因为PPs的主要作用是通过激活过氧化物酶体增殖物激活受体α（PPARα）来诱导脂肪酸氧化酶。据我们所知，尚未发现其他同时被SREBP-1和PP诱导的基因。PPARα是否直接介导这一过程还有待确定。现有数据表明，PPs对去饱和酶的诱导可能是对不饱和脂肪酸需求增加的一种代偿反应，因为PPs会增加脂肪酸降解并诱导过氧化物酶体增殖。
