Furuya Shigeki, Watanabe Masahiko
Neuronal Circuit Mechanisms Research Group, RIKEN Brain Science Institute, Wako, Saitama, Japan.
Arch Histol Cytol. 2003 May;66(2):109-21. doi: 10.1679/aohc.66.109.
L-Serine is a non-essential amino acid that can be synthesized in the body. It derives from an intermediate of the glycolytic pathway, 3-phosphoglycerate, and utilized for the syntheses of proteins, other amino acids, membrane lipids, heme, and nucleotides. Emerging evidence indicates that L-serine functions as a glia-derived trophic factor, which strongly promotes the survival and differentiation of cultured neurons. L-Serine biosynthetic enzyme 3-phosphoglycerate dehydrogenase (3PGDH) and small neutral amino acid transporter ASCT1 have been revealed to be expressed preferentially in the radial glia-astrocyte lineage and olfactory ensheathing glia of both adult and developing rodent brains. In contrast, these biosynthetic and transporter molecules for L-serine are faint or undetectable in neurons and phagocytic cells. In this review, we summarize recent progress to propose that L-serine synthesis in these glial cells and its supply to nearby neurons and other glia constitute a novel metabolic unit in the brain. Based on these neuroglial and glioglial relationships, glucose in neurons and phogocytes can be strategically used for energy production, while a variety of L-serine-derived biomolecules required for their proliferaton, survival, differentiation, and function are synthesized in and supplied from the radial glia-astrocyte lineage and olfactory ensheathing glia. A transient capillary expression of ASCT1 in fetal and neonatal brains further suggests that, in addition to the glia-borne L-serine, an active transport of blood-borne L-serine would play an essential role in neural development.
L-丝氨酸是一种人体可合成的非必需氨基酸。它源自糖酵解途径的中间产物3-磷酸甘油酸，可用于蛋白质、其他氨基酸、膜脂、血红素和核苷酸的合成。新出现的证据表明，L-丝氨酸作为一种神经胶质细胞衍生的营养因子，能强烈促进培养神经元的存活和分化。已发现L-丝氨酸生物合成酶3-磷酸甘油酸脱氢酶（3PGDH）和中性氨基酸转运体ASCT1在成年和发育中的啮齿动物大脑的放射状胶质细胞-星形胶质细胞谱系以及嗅鞘胶质细胞中优先表达。相比之下，这些L-丝氨酸的生物合成和转运分子在神经元和吞噬细胞中微弱或无法检测到。在这篇综述中，我们总结了近期的进展，提出这些胶质细胞中L-丝氨酸的合成及其向附近神经元和其他胶质细胞的供应构成了大脑中一个新的代谢单元。基于这些神经胶质细胞和胶质细胞间的关系，神经元和吞噬细胞中的葡萄糖可被策略性地用于产生能量，而它们增殖、存活、分化和发挥功能所需的各种L-丝氨酸衍生生物分子则在放射状胶质细胞-星形胶质细胞谱系和嗅鞘胶质细胞中合成并供应。胎儿和新生儿大脑中ASCT1在毛细血管中的短暂表达进一步表明，除了神经胶质细胞携带的L-丝氨酸外，血液中L-丝氨酸的主动转运在神经发育中也起着至关重要的作用。
