School of Medicine and Illawarra Health and Medical Research Institute (IHMRI) at the University of Wollongong, Wollongong, NSW 2522, Australia.
Comp Biochem Physiol B Biochem Mol Biol. 2021 Apr-May;253:110552. doi: 10.1016/j.cbpb.2020.110552. Epub 2020 Dec 24.
This is the story of a series of reductionist studies that started with an attempt to explain what underpins the high-level of aerobic metabolism in mammals (i.e. associated with the evolution of endothermy) and almost forty years later had led to investigations into the role of membrane lipids in determining metabolism. Initial studies showed that the increase in aerobic metabolism in mammals was driven by a combination of increases in mitochondrial volume and membrane densities, organ size and changes in the molecular activity of enzymes. The increase in the capacity to produce energy was matched by an increase in energy use, notably driven by increases in H, Na and K fluxes. In the case of increased Na flux, it was found this was matched by increases in Na-dependent metabolism at the tissue level and increases in enzyme activity at a cellular level but not by an increase in the number of sodium pumps. To maintain Na gradient across cell membranes, increased Na flux is not controlled by an increase in sodium pump number but rather by an increase in sodium pump molecular activity (i.e. an increase the substrate turnover rate of each sodium pump) in tissues of endotherms. This increase in molecular activity is coupled to an increase in the level of highly unsaturated polyunsaturated fatty acids (PUFA) in membranes, a mechanism similar to that used by ectotherms to ameliorate decreasing activities of metabolic processes in the cold. Determination of how changes in membrane fatty acid composition can change the activities of proteins in membranes will be the next step in this story.
这是一系列还原论研究的故事，这些研究始于试图解释支撑哺乳动物高水平有氧代谢的基础（即与温血动物的进化有关），而近四十年后，这些研究已经深入到了膜脂在决定代谢中的作用。最初的研究表明，哺乳动物有氧代谢的增加是由线粒体体积和膜密度、器官大小以及酶分子活性的变化的综合增加所驱动的。产能能力的增加与能量消耗的增加相匹配，特别是由 H、Na 和 K 通量的增加驱动的。在 Na 通量增加的情况下，发现这与组织水平上 Na 依赖性代谢的增加以及细胞水平上酶活性的增加相匹配，但与钠泵数量的增加无关。为了维持跨细胞膜的 Na 梯度，Na 通量的增加不是通过增加钠泵数量来控制，而是通过增加钠泵分子活性（即每个钠泵的底物周转率增加）来控制，在温血动物的组织中。这种分子活性的增加与膜中高度不饱和多不饱和脂肪酸（PUFA）水平的增加相关联，这一机制类似于变温动物在寒冷中用来改善代谢过程活性下降的机制。确定膜脂肪酸组成的变化如何改变膜蛋白的活性将是这个故事的下一步。
