Poole R C, Halestrap A P
Department of Biochemistry, School of Medical Sciences, University of Bristol, United Kingdom.
Am J Physiol. 1993 Apr;264(4 Pt 1):C761-82. doi: 10.1152/ajpcell.1993.264.4.C761.
Transport of L-lactate across the plasma membrane is of considerable importance to almost all mammalian cells. In most cells a specific H(+)-monocarboxylate cotransporter is largely responsible for this process; the capacity of this carrier is usually very high, to support the high rates of production or utilization of L-lactate. The best characterized H(+)-monocarboxylate transporter is that of the erythrocyte membrane, which transports L-lactate and a wide range of other aliphatic monocarboxylates, including pyruvate and the ketone bodies acetoacetate and beta-hydroxybutyrate. This carrier is inhibited by alpha-cyanocinnamate derivatives and some stilbene disulfonates and has been identified as a protein of 35-50 kDa on the basis of purification and specific labeling experiments. Other cells possess similar alpha-cyanocinnamate-sensitive H(+)-linked monocarboxylate transporters, but in some cases there are significant differences in the properties of these systems, sufficient to suggest the existence of a family of such carriers. In particular, cardiac muscle and tumor cells have transporters that differ in their Km values for certain substrates (including stereoselectivity for L- over D-lactate) and in their sensitivity to inhibitors. Mitochondria, bacteria, and yeast also possess H(+)-monocarboxylate transporters that share some properties in common with those in the mammalian plasma membrane but are adapted to their specific roles. However, there are distinct Na(+)-monocarboxylate cotransporters on the luminal surface of intestinal and kidney epithelia, which enable active uptake of lactate, pyruvate, and ketone bodies in these tissues. This article reviews the properties of these transport systems and their role in mammalian metabolism.
L-乳酸跨质膜的转运对几乎所有哺乳动物细胞都极为重要。在大多数细胞中，一种特定的H⁺-单羧酸共转运蛋白在很大程度上负责这一过程；该载体的转运能力通常非常高，以支持L-乳酸的高生成或利用速率。研究最为透彻的H⁺-单羧酸转运蛋白是红细胞膜上的转运蛋白，它能转运L-乳酸以及多种其他脂肪族单羧酸，包括丙酮酸和酮体乙酰乙酸及β-羟基丁酸。该载体受到α-氰基肉桂酸衍生物和一些芪二磺酸盐的抑制，并且基于纯化和特异性标记实验已被鉴定为一种35 - 50 kDa的蛋白质。其他细胞也拥有类似的对α-氰基肉桂酸敏感的H⁺连接的单羧酸转运蛋白，但在某些情况下，这些系统的特性存在显著差异，足以表明存在这样一族载体。特别是，心肌细胞和肿瘤细胞的转运蛋白在某些底物的Km值（包括对L-乳酸与D-乳酸的立体选择性）及其对抑制剂的敏感性方面存在差异。线粒体、细菌和酵母也拥有H⁺-单羧酸转运蛋白，它们与哺乳动物质膜上的转运蛋白有一些共同特性，但适应于各自的特定作用。然而，在肠道和肾上皮细胞的管腔表面存在不同的Na⁺-单羧酸共转运蛋白，这使得这些组织能够主动摄取乳酸、丙酮酸和酮体。本文综述了这些转运系统的特性及其在哺乳动物新陈代谢中的作用。
