Coleman Chandra M, Neckameyer Wendi S
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 S. Grand Blvd, St. Louis, MO 63104, USA.
Invert Neurosci. 2004 Oct;5(2):85-96. doi: 10.1007/s10158-004-0031-y. Epub 2004 Oct 6.
In Drosophila melanogaster, serotonin (5-hydroxytryptamine, 5-HT) is required for both very early non-neuronal developmental events, and in the CNS as a neurotransmitter to modulate behavior. 5-HT is synthesized, at least in part, by the actions of Drosophila tryptophan-phenylalanine hydroxylase (DTPH), a dual function enzyme that hydroxylates both phenylalanine and tryptophan. DTPH is expressed in numerous tissues as well as dopaminergic and serotonergic neurons, but it does not necessarily function as both enzymes in these tissues. Deficiencies in DTPH could affect the production of dopamine and serotonin, and thus dopaminergic and serotonergic signaling pathways. In this paper, we show that DTPH exhibits differential hydroxylase activity based solely on substrate. When DTPH uses phenylalanine as a substrate, regulatory control (end product inhibition, decreased PAH activity following phosphorylation, catecholamine inhibition) is observed that is not seen when the enzyme uses tryptophan as a substrate. These studies suggest that regulation of DTPH enzymatic activity occurs, at least in part, through the actions of its substrate.
在黑腹果蝇中，血清素（5-羟色胺，5-HT）对于非常早期的非神经元发育事件以及在中枢神经系统中作为调节行为的神经递质都是必需的。5-HT至少部分是由果蝇色氨酸-苯丙氨酸羟化酶（DTPH）的作用合成的，DTPH是一种双功能酶，可将苯丙氨酸和色氨酸都羟基化。DTPH在许多组织以及多巴胺能和5-羟色胺能神经元中表达，但它在这些组织中不一定同时作为两种酶起作用。DTPH的缺陷可能会影响多巴胺和血清素的产生，从而影响多巴胺能和5-羟色胺能信号通路。在本文中，我们表明DTPH仅基于底物表现出不同的羟化酶活性。当DTPH使用苯丙氨酸作为底物时，会观察到调节控制（终产物抑制、磷酸化后PAH活性降低、儿茶酚胺抑制），而当该酶使用色氨酸作为底物时则不会出现这种情况。这些研究表明，DTPH酶活性的调节至少部分是通过其底物的作用来实现的。
