The solute carrier family 16 (SLC16) is comprised of 14 members of the monocarboxylate transporter (MCT) family that play an essential role in the transport of important cell nutrients and for cellular metabolism and pH regulation. MCTs 1-4 have been extensively studied and are involved in the proton-dependent transport of L-lactate, pyruvate, short-chain fatty acids, and monocarboxylate drugs in a wide variety of tissues. MCTs 1 and 4 are overexpressed in a number of cancers, and current investigations have focused on transporter inhibition as a novel therapeutic strategy in cancers. MCT1 has also been used in strategies aimed at enhancing drug absorption due to its high expression in the intestine. Other MCT isoforms are less well characterized, but ongoing studies indicate that MCT6 transports xenobiotics such as bumetanide, nateglinide, and probenecid, whereas MCT7 has been characterized as a transporter of ketone bodies. MCT8 and MCT10 transport thyroid hormones, and recently, MCT9 has been characterized as a carnitine efflux transporter and MCT12 as a creatine transporter. Expressed at the blood brain barrier, MCT8 mutations have been associated with an X-linked intellectual disability, known as Allan-Herndon-Dudley syndrome. Many MCT isoforms are associated with hormone, lipid, and glucose homeostasis, and recent research has focused on their potential roles in disease, with MCTs representing promising novel therapeutic targets. This review will provide a summary of the current literature focusing on the characterization, function, and regulation of the MCT family isoforms and on their roles in drug disposition and in health and disease. SIGNIFICANCE STATEMENT: The 14-member solute carrier family 16 of monocarboxylate transporters (MCTs) plays a fundamental role in maintaining intracellular concentrations of a broad range of important endogenous molecules in health and disease. MCTs 1, 2, and 4 (L-lactate transporters) are overexpressed in cancers and represent a novel therapeutic target in cancer. Recent studies have highlighted the importance of MCTs in glucose, lipid, and hormone homeostasis, including MCT8 in thyroid hormone brain uptake, MCT12 in carnitine transport, and MCT11 in type 2 diabetes.

中文翻译：

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单羧酸盐转运蛋白（SLC16）：在健康和疾病中的功能，调控和作用。

溶质载体家族16（SLC16）由单羧酸盐转运蛋白（MCT）家族的14个成员组成，这些成员在重要细胞营养物质的转运以及细胞代谢和pH调节中起着至关重要的作用。MCT 1-4已被广泛研究，并参与各种组织中L-乳酸，丙酮酸，短链脂肪酸和单羧酸盐药物的质子依赖性转运。MCT 1和4在许多癌症中过表达，目前的研究集中在转运蛋白抑制作为一种新的癌症治疗策略。由于MCT1在肠道中的高表达，它也已用于增强药物吸收的策略中。其他MCT同工型的表征较差，但正在进行的研究表明MCT6可以转运异种生物，如布美他尼，那格列奈，和丙磺舒，而MCT7已被表征为酮体的转运蛋白。MCT8和MCT10转运甲状腺激素，最近，MCT9被表征为肉碱外排转运蛋白，MCT12被表征为肌酸转运蛋白。在血脑屏障中表达的MCT8突变与X连锁的智力障碍有关，称为Allan-Herndon-Dudley综合征。许多MCT亚型与激素，脂质和葡萄糖体内稳态相关，最近的研究集中在它们在疾病中的潜在作用，其中MCT代表了有希望的新型治疗靶标。这篇综述将提供有关MCT家族同工型的特征，功能和调控及其在药物处置以及健康和疾病中作用的最新文献的摘要。重要声明：单羧酸盐转运蛋白（MCT）的14人溶质载体家族16在维持健康和疾病中广泛的重要内源性分子的细胞内浓度方面起着基本作用。MCT 1，2和4（L乳酸盐转运蛋白）在癌症中过表达，代表癌症中的一种新型治疗靶点。最近的研究强调了MCT在葡萄糖，脂质和激素稳态中的重要性，包括甲状腺激素脑摄取中的MCT8，肉碱运输中的MCT12和2型糖尿病中的MCT11。和4（L-乳酸转运蛋白）在癌症中过表达，代表癌症中的新治疗靶点。最近的研究强调了MCT在葡萄糖，脂质和激素稳态中的重要性，包括甲状腺激素脑摄取中的MCT8，肉碱运输中的MCT12和2型糖尿病中的MCT11。和4（L-乳酸转运蛋白）在癌症中过表达，代表癌症中的新治疗靶点。最近的研究强调了MCT在葡萄糖，脂质和激素稳态中的重要性，包括甲状腺激素脑摄取中的MCT8，肉碱运输中的MCT12和2型糖尿病中的MCT11。