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Regulation of fatty acid and cholesterol synthesis: co-operation or competition?
Progress in Lipid Research ( IF 13.6 ) Pub Date : 2003-10-16 , DOI: 10.1016/s0163-7827(03)00034-1
Geoffrey F Gibbons 1
Affiliation  

Fatty acids and sterols originally evolved symbiotically as structural components of cell membranes. In some respects, control of their biosynthetic pathways reflects their mutual interdependence in defining changes in the physicochemical properties of the membranes in response to the changing internal and external cellular environments. In some tissues of higher animals, however, cholesterol and fatty acids have multifunctional roles. In particular, the liver synthesizes these lipids for export as multimolecular complexes in the form of micellar bile components and lipoproteins. Intrahepatic fatty acid and cholesterol synthesis is dependent upon the balance between hepatic output of these complexes and dietary input of fat and cholesterol. Thus physiological control of these synthetic processes is often co-ordinated at both the transcriptional and post-translational levels. On the other hand, changes in flux through major metabolic pathways, particularly during physiological transitions and as a result of genetic manipulation, affects substrate availability for these pathways. Under these circumstances, regulation reflects a compensatory response to ensure that flux through the lipid pathways remains unchanged. These regulatory changes can best be interpreted in terms of a Metabolic Control Analysis approach. In summary, flux through the fatty acid and cholesterol pathways reflects (a) cellular demand for these lipids, (b) a variable availability of substrates, (c) a combination of (a) and (b).

中文翻译:

调节脂肪酸和胆固醇的合成:合作还是竞争?

脂肪酸和固醇最初是作为细胞膜的结构成分共生地进化的。在某些方面,对它们的生物合成途径的控制反映了它们在确定响应于内部和外部细胞环境变化的膜的物理化学性质变化中的相互依赖性。然而,在高等动物的某些组织中,胆固醇和脂肪酸具有多种功能。特别地,肝脏合成这些脂质以胶束胆汁成分和脂蛋白的形式作为多分子复合物输出。肝内脂肪酸和胆固醇的合成取决于这些复合物的肝输出量与饮食中脂肪和胆固醇的输入量之间的平衡。因此,通常在转录和翻译后水平上协调这些合成过程的生理控制。另一方面,通过主要代谢途径的通量变化,特别是在生理转变过程中以及由于遗传操作,会影响这些途径的底物利用率。在这种情况下,调节反映出补偿反应,以确保通过脂质途径的通量保持不变。这些调节变化最好用代谢控制分析方法来解释。总而言之,通过脂肪酸和胆固醇途径的通量反映了(a)细胞对这些脂质的需求,(b)底物的可变利用率,(c)(a)和(b)的组合。通过主要代谢途径的通量变化,尤其是在生理转变过程中以及由于遗传操作,会影响这些途径的底物利用率。在这种情况下,调节反映出补偿反应,以确保通过脂质途径的通量保持不变。这些调节变化最好用代谢控制分析方法来解释。总而言之,通过脂肪酸和胆固醇途径的通量反映了(a)细胞对这些脂质的需求,(b)底物的可变利用率,(c)(a)和(b)的组合。通过主要代谢途径的通量变化,特别是在生理转变过程中以及由于遗传操作,会影响这些途径的底物利用率。在这种情况下,调节反映出补偿反应,以确保通过脂质途径的通量保持不变。这些调节变化最好用代谢控制分析方法来解释。总而言之,通过脂肪酸和胆固醇途径的通量反映了(a)细胞对这些脂质的需求,(b)底物的可变利用率,(c)(a)和(b)的组合。调节反映了补偿反应,以确保通过脂质途径的通量保持不变。这些调节变化最好用代谢控制分析方法来解释。总而言之,通过脂肪酸和胆固醇途径的通量反映了(a)细胞对这些脂质的需求,(b)底物的可变利用率,(c)(a)和(b)的组合。调节反映了补偿反应,以确保通过脂质途径的通量保持不变。这些调节变化最好用代谢控制分析方法来解释。总而言之,通过脂肪酸和胆固醇途径的通量反映了(a)细胞对这些脂质的需求,(b)底物的可变利用率,(c)(a)和(b)的组合。
更新日期:2019-11-01
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