Cell-cell and intracellular lactate shuttles
Cell-cell and intracellular lactate shuttles
复制标题
DOI：
10.1113/jphysiol.2009.178350
复制
发表时间：
2009-12-01
影响因子：
5.5
通讯作者：
Brooks, George A.
中科院分区：
文献类型：
--
作者：
Brooks, George A.
曾经被认为是骨骼肌收缩时缺氧的结果，糖酵解产物乳酸盐在完全有氧条件下在各种细胞中连续形成和利用。“细胞-细胞”和“细胞内乳酸穿梭”概念描述了乳酸在传递氧化和致炎底物以及细胞信号传导中的作用。细胞-细胞穿梭的实例包括工作肌床内的白色糖酵解纤维和红色氧化纤维之间以及工作骨骼肌与心脏、脑、肝脏和肾脏之间的乳酸盐交换。细胞内乳酸穿梭的实例包括线粒体的乳酸摄取和过氧化物酶体中用于乳酸交换的丙酮酸。乳酸与丙酮酸的交换影响细胞的氧化还原状态，乳酸本身就是一种活性氧产生器。在体内，乳酸盐是优选的底物，高血乳酸盐水平下调葡萄糖和游离脂肪酸（FFA）的使用。同样，乳酸盐结合可能影响代谢调节，例如与脂肪细胞中的G蛋白受体结合抑制脂解，从而降低血浆FFA可用性。体外乳酸蓄积上调骨骼肌中MCT 1和编码线粒体网其他组分的基因的表达。肌肉中的线粒体网和其他有氧组织中的线粒体网络的功能是建立具有高线粒体密度的细胞氧化乳酸所必需的浓度和质子梯度。乳酸穿梭的存在使人们认识到，糖酵解和氧化途径应被视为相关联的，而不是替代的过程，因为乳酸，一种途径的产物，是另一种途径的底物。
Once thought to be the consequence of oxygen lack in contracting skeletal muscle, the glycolytic product lactate is formed and utilized continuously in diverse cells under fully aerobic conditions. 'Cell-cell' and 'intracellular lactate shuttle' concepts describe the roles of lactate in delivery of oxidative and gluconeogenic substrates as well as in cell signalling. Examples of the cell-cell shuttles include lactate exchanges between between white-glycolytic and red-oxidative fibres within a working muscle bed, and between working skeletal muscle and heart, brain, liver and kidneys. Examples of intracellular lactate shuttles include lactate uptake by mitochondria and pyruvate for lactate exchange in peroxisomes. Lactate for pyruvate exchanges affect cell redox state, and by itself lactate is a ROS generator. In vivo, lactate is a preferred substrate and high blood lactate levels down-regulate the use of glucose and free fatty acids (FFA). As well, lactate binding may affect metabolic regulation, for instance binding to G-protein receptors in adipocytes inhibiting lipolysis, and thus decreasing plasma FFA availability. In vitro lactate accumulation upregulates expression of MCT1 and genes coding for other components of the mitochondrial reticulum in skeletal muscle. The mitochondrial reticulum in muscle and mitochondrial networks in other aerobic tissues function to establish concentration and proton gradients necessary for cells with high mitochondrial densities to oxidize lactate. The presence of lactate shuttles gives rise to the realization that glycolytic and oxidative pathways should be viewed as linked, as opposed to alternative, processes, because lactate, the product of one pathway, is the substrate for the other.