Grima B, Lamouroux A, Boni C, Julien J F, Javoy-Agid F, Mallet J
Nature. 1987;326(6114):707-11. doi: 10.1038/326707a0.
Catecholaminergic systems in discrete regions of the brain are thought to be important in affective psychoses, learning and memory, reinforcement and sleep-wake cycle regulation. Tyrosine hydroxylase (TH) is the first enzyme in the pathway of catecholamine synthesis. Its importance is reflected in the diversity of the mechanisms that have been described which control its activity; TH levels vary both during development and as a function of the activity of the nervous system. Recently, we deduced the complete amino-acid sequence of rat TH from a complementary DNA clone encoding a functional enzyme. Here we demonstrate that, in man, TH molecules are encoded by at least three distinct messenger RNAs. The expression of these mRNAs varies in different parts of the nervous system. The sequence differences observed are confined to the 5' termini of the messengers and involve alternative splicing events. This variation has clear functional consequences for each putative form of the enzyme and could represent a novel means of regulating catecholamine levels in normal and pathological neurons.
大脑离散区域中的儿茶酚胺能系统被认为在情感性精神病、学习与记忆、强化以及睡眠-觉醒周期调节中起重要作用。酪氨酸羟化酶（TH）是儿茶酚胺合成途径中的首个酶。其重要性体现在已描述的控制其活性的多种机制中；TH水平在发育过程中以及作为神经系统活动的函数而变化。最近，我们从编码功能性酶的互补DNA克隆中推导了大鼠TH的完整氨基酸序列。在此我们证明，在人类中，TH分子由至少三种不同的信使RNA编码。这些mRNA的表达在神经系统的不同部位有所不同。观察到的序列差异局限于信使的5'末端，并且涉及可变剪接事件。这种变异对该酶的每种假定形式都有明显的功能后果，并且可能代表一种调节正常和病理神经元中儿茶酚胺水平的新手段。
