DOPAMINE BIOSYNTHESIS FROM L-TYROSINE AND L-PHENYLALANINE IN RAT-BRAIN SYNAPTOSOMES - PREFERENTIAL USE OF NEWLY ACCUMULATED PRECURSORS
DOPAMINE BIOSYNTHESIS FROM L-TYROSINE AND L-PHENYLALANINE IN RAT-BRAIN SYNAPTOSOMES - PREFERENTIAL USE OF NEWLY ACCUMULATED PRECURSORS
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DOI：
10.1111/j.1471-4159.1977.tb10675.x
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发表时间：
1977-01-01
影响因子：
4.7
通讯作者：
ZIGMOND, M
中科院分区：
文献类型：
--
作者：
KAPATOS, G;ZIGMOND, M
用大鼠纹状体和嗅结节的突触体研究了L-酪氨酸（Tyr）和L-苯丙氨酸（Phe）生物合成多巴胺（DA）的过程。14CO2的形成从羧基标记的前体发生专门的突触体内羟基化和随后的脱羧。DA形成的最适pH值为6.2，并且与前体和组织来源无关。当pH值超过此最佳值时，Tyr的合成比Phe的合成下降得更快。合成服从Michaelis-Menton动力学时，表示为在介质中的前体的比活性的函数。其特征在于总Km（约0.9 μ M），其不依赖于前体和组织来源，并且显著低于突触体积累前体的Kt（Tyr和Phe分别为15.3和13.3 μ M）。虽然每种前体都是从相反的标记氨基酸合成DA的非竞争性抑制剂，但Tyr是从Phe合成的更有效的抑制剂（Ki = 1.5 μ M），而Phe是从Tyr合成的抑制剂（Ki = 9.2 μ M）。色氨酸竞争性抑制合成（对于Tyr和Phe的合成，Ki分别为15.2和13.2 μ M），DA非竞争性抑制（对于Tyr和Phe，Ki分别为1.1和0.42 μ M）。提出了一个突触体内DA合成的模型，试图整合这些数据。这种模式的一个主要特点是新积累的前体不会迅速与内源性前体池混合，而是优先转化为DA。
The biosynthesis of dopamine (DA) from L-tyrosine (Tyr) and L-phenylalanine (Phe) was investigated using synaptosomes prepared from the striatum and olfactory tubercle of the rat. The formation of 14CO2 from either carboxyl labeled precursor occurred exclusively within the synaptosome following hydroxylation and subsequent decarboxylation. The optimum pH for the formation of DA was 6.2 and was independent of precursor and tissue source. As pH increased beyond this optimum, synthesis from Tyr declined more rapidly than that from Phe. Synthesis obeyed Michaelis-Menton kinetics when expressed as a function of the specific activity of precursor in the medium. It was characterized by an overall Km (approximately 0.9 .mu.M) which was independent of precursor and tissue source, and was considerably lower than the Kt for accumulation of precursor by synaptosomes (15.3 and 13.3 .mu.M for Tyr and Phe, respectively). While each precursor was an uncompetitive inhibitor of DA synthesis from the opposing labeled amino acid, Tyr was a more effective inhibitor of synthesis from Phe (Ki = 1.5 .mu.M) than was Phe an inhibitor of synthesis from Tyr (Ki = 9.2 .mu.M). Tryptophan inhibited synthesis competitively (Ki = 15.2 and 13.2 .mu.M for synthesis from Tyr and Phe, respectively), and DA inhibited non-competitively (Ki = 1.1 and 0.42 .mu.M for Tyr and Phe, respectively). A model of DA synthesis within the synaptosome was presented which attempts to integrate these data. A major feature of this schema was the proposal that newly accumulated precursor does not mix rapidly with endogenous precursor pools but rather is preferentially converted to DA.