Yao D, Mackenzie B, Ming H, Varoqui H, Zhu H, Hediger M A, Erickson J D
Neuroscience Center and the Departments of Opthalmology and Pharmacology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
J Biol Chem. 2000 Jul 28;275(30):22790-7. doi: 10.1074/jbc.M002965200.
A cDNA clone encoding a plasma membrane alanine-preferring transporter (SAT2) has been isolated from glutamatergic neurons in culture and represents the second member of the system A family of neutral amino acid transporters. SAT2 displays a widespread distribution and is expressed in most tissues, including heart, adrenal gland, skeletal muscle, stomach, fat, brain, spinal cord, colon, and lung, with lower levels detected in spleen. No signal is detected in liver or testis. In the central nervous system, SAT2 is expressed in neurons. SAT2 is significantly up-regulated during differentiation of cerebellar granule cells and is absent from astrocytes in primary culture. The functional properties of SAT2, examined using transfected fibroblasts and in cRNA-injected voltage-clamped Xenopus oocytes, show that small aliphatic neutral amino acids are preferred substrates and that transport is voltage- and Na(+)-dependent (1:1 stoichiometry), pH-sensitive, and inhibited by alpha-(methylamino)isobutyric acid (MeAIB), a specific inhibitor of system A. Kinetic analyses of alanine and MeAIB uptake by SAT2 are saturable, with Michaelis constants (K(m)) of 200-500 microm. In addition to its ubiquitous role as a substrate for oxidative metabolism and a major vehicle of nitrogen transport, SAT2 may provide alanine to function as the amino group donor to alpha-ketoglutarate to provide an alternative source for neurotransmitter synthesis in glutamatergic neurons.
一个编码质膜丙氨酸偏好转运体（SAT2）的cDNA克隆已从培养的谷氨酸能神经元中分离出来，它是中性氨基酸转运体A系统家族的第二个成员。SAT2分布广泛，在大多数组织中都有表达，包括心脏、肾上腺、骨骼肌、胃、脂肪、脑、脊髓、结肠和肺，在脾脏中检测到的水平较低。在肝脏或睾丸中未检测到信号。在中枢神经系统中，SAT2在神经元中表达。在小脑颗粒细胞分化过程中，SAT2显著上调，原代培养的星形胶质细胞中不存在SAT2。使用转染的成纤维细胞和注射cRNA的电压钳制非洲爪蟾卵母细胞对SAT2的功能特性进行检测，结果表明，小的脂肪族中性氨基酸是其偏好底物，转运是电压和Na⁺依赖性的（化学计量比为1:1），对pH敏感，并受到系统A的特异性抑制剂α-（甲基氨基）异丁酸（MeAIB）的抑制。对SAT2摄取丙氨酸和MeAIB的动力学分析具有饱和性，米氏常数（Kₘ）为200 - 500微摩尔。除了作为氧化代谢底物和氮转运的主要载体这一普遍作用外，SAT2还可能提供丙氨酸作为α-酮戊二酸的氨基供体，为谷氨酸能神经元中的神经递质合成提供替代来源。
