摘要
柠檬酸是细胞内代谢的主要基质之一。柠檬酸盐在血液的胞外水平是稳定的,但局部有所不同,在大脑水平略有增加和在前列腺中处于高的水平。最近代谢组学的研究表明,柠檬酸水平是不同的病理生理状态的潜在的预兆;其降低已与男性不育症,脑部疾病和转移性癌症相关。 在这篇综述中,我们讨论了柠檬酸作为精子的能量底物的作用。我们也叙述了在神经元的正常运行下星形胶质细胞释放的柠檬酸的功能。从而,我们提出神经元质膜柠檬酸转运在精神疾病中的潜在作用。最后,我们回顾血液,尿液和组织柠檬酸水平癌症患者最近的有关出版物研究,推测出细胞外柠檬酸是支持癌细胞的新陈代谢转移的关键。 尽管胞外柠檬酸盐在生理和病理过程中的重要性,令人惊讶知之甚少的是柠檬酸在专门的细胞的合成和柠檬酸盐转运体如何控制柠檬酸穿过各膜运动。通过对星形胶质细胞中的柠檬酸转运体的分子起源的测定,精子和癌细胞可能提供新的治疗靶点和药理调节柠檬酸释放和摄取的可能,以防止男性不育症,治疗精神疾病和目标癌症。
关键词: 星形细胞, 癌症, 柠檬酸盐, 神经元, 细胞膜转运蛋白, 前列腺, 精子
Current Molecular Medicine
Title:Extracellular Citrate in Health and Disease
Volume: 15 Issue: 10
Author(s): M. E. Mycielska, V. M. Milenkovic, C. H. Wetzel, P. Rümmele and E. K. Geissler
Affiliation:
关键词: 星形细胞, 癌症, 柠檬酸盐, 神经元, 细胞膜转运蛋白, 前列腺, 精子
摘要: Citrate is one of the major substrates for intracellular metabolism. The extracellular level of citrate is stable in blood but varies locally, with slightly increased levels in brain and high levels in prostate. Recent metabolomics research suggests that citrate level is a potential harbinger of different pathophysiological states; its decrease has been correlated with male infertility, brain diseases and metastatic cancer.
In this review we discuss the role of citrate as an energy substrate for sperm. We also review the function of citrate released by astrocytes in the normal operation of neurons, and consequently we suggest a potential role of neuronal plasma membrane citrate transporters in mental disorders. Finally, we review recent relevant publications studying blood, urine and tissue citrate levels in cancer patients and hypothesize that extracellular citrate supports cancer cell metabolism critical for metastasis.
Despite the importance of extracellular citrate in physiological and pathophysiological processes, surprisingly little is known about citrate synthesis in specialized cells, or about citrate transporters controlling citrate movement across various membranes. Determination of the molecular origin of citrate transporters in astrocytes, sperm and cancer cells could offer novel therapeutic targets and the possibility to pharmacologically regulate citrate release and uptake for preventing male infertility, treating mental diseases and targeting cancer.
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Cite this article as:
M. E. Mycielska, V. M. Milenkovic, C. H. Wetzel, P. Rümmele and E. K. Geissler , Extracellular Citrate in Health and Disease, Current Molecular Medicine 2015; 15 (10) . https://dx.doi.org/10.2174/1566524016666151123104855
DOI https://dx.doi.org/10.2174/1566524016666151123104855 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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