Lactate shuttles in nature
Lactate shuttles in nature
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DOI：
10.1042/bst0300258
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发表时间：
2002-04-01
影响因子：
3.9
通讯作者：
Brooks, GA
中科院分区：
文献类型：
--
作者：
Brooks, GA
曾经被认为是骨骼肌收缩缺氧的结果，糖酵解产物乳酸在完全有氧条件下形成和持续利用。“细胞-细胞”和“细胞内乳酸穿梭”的概念描述了乳酸在氧化和糖异生底物的传递以及细胞信号传导中的作用。细胞-细胞穿梭的例子包括工作肌肉床内白色糖酵解纤维和红色氧化纤维之间的乳酸交换，工作骨骼肌和心脏之间的乳酸交换，以及净乳酸释放和糖异生组织之间的乳酸交换。星形胶质细胞和神经元之间的乳酸交换与大脑中的谷氨酸能信号传导有关，这是支持细胞-细胞信号传导的乳酸穿梭的一个例子。线粒体的乳酸摄取和过氧化物酶体的丙酮酸-乳酸交换是细胞内乳酸穿梭的例子。乳酸在产生位点和去除位点之间的交换由单羧酸转运蛋白促进，其中有几种同种异构体，也可能由支架蛋白促进。线粒体乳酸-丙酮酸转运蛋白似乎与线粒体乳酸脱氢酶一起工作，这使得乳酸在活跃呼吸细胞内被氧化。因此，线粒体的功能是建立具有高线粒体密度的细胞（如心肌细胞）摄取和氧化乳酸所需的浓度和质子梯度。在工作的心脏和骨骼肌床上的动静脉差异测量以及这些组织的核磁共振光谱分析表明，乳酸在体内形成细胞内形成和氧化。细胞内的糖酵解和乳酸氧化允许高通量速率和维持细胞质和线粒体的氧化还原平衡。细胞内乳酸穿梭的其他例子包括精子线粒体的乳酸摄取和氧化，以及丙酮酸-乳酸交换促进过氧化物酶体的β -氧化。通过观察酿酒酵母的线粒体含有黄酮色素b(2)一种乳酸细胞色素c氧化还原酶，该酶将乳酸脱氢与细胞色素c的还原结合起来，这一发现暗示了乳酸穿梭的古老起源。细胞-细胞和细胞内乳酸穿梭的存在提出了糖酵解和氧化途径可以被视为相互关联的概念，而不是替代的过程，因为乳酸是一种途径的产物，是另一个的底物。
Once thought to be the consequence of oxygen lack in contracting skeletal muscle, the glycolytic product lactate is formed and utilized continuously under fully aerobic conditions. 'Cell-cell' and 'intracellular lactate shuttle' concepts describe the roles of lactate in the delivery of oxidative and gluconeogenic substrates, as well as in cell signalling. Examples of cell-cell shuttles include lactate exchanges between,white-glycolytic and red-oxidative fibres within a working muscle bed, between working skeletal muscle and heart, and between tissues of net lactate release and gluconeogenesis. Lactate exchange between astroctes and neurons that is linked to glutamatergic signalling in the brain is an example of a lactate shuttle supporting cell-cell signalling. Lactate uptake by mitochondria and pyruvate-lactate exchange in peroxisomes are examples of intracellular lactate shuttles. Lactate exchange between sites of production and removal is facilitated by monocarboxylate transport proteins, of which there are several isoforms, and, probably, also by scaffolding proteins. The mitochondrial lactate-pyruvate transporter appears to work in conjunction with mitochondrial lactate dehydrogenase, which permits lactate to be oxidized within actively respiring cells. Hence mitochondria function to establish the concentration and proton gradients necessary for cells with high mitochondrial densities (e.g. cardiocytes) to take up and oxidize lactate. Arteriovenous difference measurements on working cardiac and skeletal muscle beds as well as NMR spectral analyses of these tissues show that lactate is formed and oxidized within the cells of formation in vivo. Glycolysis and lactate oxidation within cells permits high flux rates and the maintenance of redox balance in the cytosol and mitochondria. Other examples of intracellular lactate shuttles include lactate uptake and oxidation in sperm mitochondria and the facilitation of beta-oxidation in peroxisomes by pyruvate-lactate exchange. An ancient origin to the utility of lactate shuttling is implied by the observation that mitochondria of Saccharomyces cerevisiae contain flavocvtochrome b(2) a lactatecytochrome c oxidoreductase that couples lactate dehydrogenation to the reduction of cytochrome c. The presence of cell-cell and intracellular lactate shuttles gives rise to the notion that glycolytic and oxidative pathways can be viewed as linked, as opposed to alternative, processes, because lactate, the product of one pathway, is the substrate for the other.