Institute of Biotechnology of the Czech Academy of Sciences, Prumyslova 595, 252 50 Vestec, Prague-West, Czech Republic.
CLIP (Childhood Leukaemia Investigation Prague), Department of Pediatric Hematology and Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
Biochim Biophys Acta Mol Basis Dis. 2024 Dec;1870(8):167451. doi: 10.1016/j.bbadis.2024.167451. Epub 2024 Aug 5.
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.
天冬氨酸是一种蛋白质合成的非必需氨基酸，在增殖细胞中具有多种必需功能。它主要通过谷氨酸草酰乙酸转氨酶 1 或 2（GOT1 或 GOT2）从草酰乙酸在细胞自主方式产生，但在某些情况下，它也可以通过 SLC1A3 等转运体或通过巨胞饮作用从微环境中回收。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。我们讨论了有利于天冬氨酸摄取的条件，以及肿瘤和骨髓微环境中外源天冬氨酸的可能来源，大多数现有数据都是在这些部位产生的。我们强调了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进行癌症治疗的可能方法。
