Abstract:
Aspartate is a proteinogenic non-essential amino acid with several essential functions in proliferating cells. It is mostly produced in a cell autonomous manner from oxalacetate via glutamate oxalacetate transaminases 1 or 2 (GOT1 or GOT2), but in some cases it can also be salvaged from the microenvironment via transporters such as SLC1A3 or by macropinocytosis. In this review we provide an overview of biosynthetic pathways that produce aspartate endogenously during proliferation. We discuss conditions that favor aspartate uptake as well as possible sources of exogenous aspartate in the microenvironment of tumors and bone marrow, where most available data have been generated. We highlight metabolic fates of aspartate, its various functions, and possible approaches to target aspartate metabolism for cancer therapy.
摘要:
天冬氨酸是一种在增殖细胞中具有几种基本功能的蛋白质非必需氨基酸。它主要是通过谷氨酸草酸盐转氨酶1或2(GOT1或GOT2)以细胞自主方式从草酸盐产生,但在某些情况下,它也可以通过转运蛋白(如SLC1A3)或通过大胞吞作用从微环境中挽救。在这篇综述中,我们概述了在增殖过程中内源性产生天冬氨酸的生物合成途径。我们讨论了肿瘤和骨髓微环境中有利于天冬氨酸摄取的条件以及外源性天冬氨酸的可能来源,在那里生成了大多数可用数据。我们强调天冬氨酸的代谢命运,它的各种功能,以及靶向天冬氨酸代谢用于癌症治疗的可能方法。