Peluso G, Nicolai R, Reda E, Benatti P, Barbarisi A, Calvani M
Institute of Protein Biochemistry and Enzymology (I.B.P.E.) CNR, Naples, Italy.
J Cell Physiol. 2000 Mar;182(3):339-50. doi: 10.1002/(SICI)1097-4652(200003)182:3<339::AID-JCP4>3.0.CO;2-B.
An efficient regulation of fuel metabolism in response to internal and environmental stimuli is a vital task that requires an intact carnitine system. The carnitine system, comprehensive of carnitine, its derivatives, and proteins involved in its transformation and transport, is indispensable for glucose and lipid metabolism in cells. Two major functions have been identified for the carnitine system: (1) to facilitate entry of long-chain fatty acids into mitochondria for their utilization in energy-generating processes; (2) to facilitate removal from mitochondria of short-chain and medium-chain fatty acids that accumulate as a result of normal and abnormal metabolism. In cancer patients, abnormalities of tumor tissue as well as nontumor tissue metabolism have been observed. Such abnormalities are supposed to contribute to deterioration of clinical status of patients, or might induce cancerogenesis by themselves. The carnitine system appears abnormally expressed both in tumor tissue, in such a way as to greatly reduce fatty acid beta-oxidation, and in nontumor tissue. In this view, the study of the carnitine system represents a tool to understand the molecular basis underlying the metabolism in normal and cancer cells. Some important anticancer drugs contribute to dysfunction of the carnitine system in nontumor tissues, which is reversed by carnitine treatment, without affecting anticancer therapeutic efficacy. In conclusion, a more complex approach to mechanisms that underlie tumor growth, which takes into account the altered metabolic pathways in cancer disease, could represent a challenge for the future of cancer research.
响应内部和环境刺激对燃料代谢进行有效调节是一项至关重要的任务，这需要完整的肉碱系统。肉碱系统包括肉碱、其衍生物以及参与其转化和运输的蛋白质，对细胞中的葡萄糖和脂质代谢不可或缺。肉碱系统已被确定有两个主要功能：（1）促进长链脂肪酸进入线粒体，以便在能量产生过程中加以利用；（2）促进短链和中链脂肪酸从线粒体中清除，这些脂肪酸是正常和异常代谢积累的产物。在癌症患者中，已观察到肿瘤组织以及非肿瘤组织代谢的异常。这种异常被认为会导致患者临床状况恶化，或者可能自身诱发癌症。肉碱系统在肿瘤组织中似乎异常表达，从而极大地降低脂肪酸β氧化，在非肿瘤组织中也是如此。从这个角度来看，对肉碱系统的研究是理解正常细胞和癌细胞代谢分子基础的一种手段。一些重要的抗癌药物会导致非肿瘤组织中肉碱系统功能障碍，肉碱治疗可逆转这种情况，且不影响抗癌治疗效果。总之，一种更复杂的方法来研究肿瘤生长的机制，考虑到癌症疾病中改变的代谢途径，可能是癌症研究未来面临的一个挑战。
