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二氢蝶啶还原酶:对儿茶酚胺生物合成调节的影响

Dihydropteridine reductase: implication on the regulation of catecholamine biosynthesis.

作者信息

Musacchio J M, D'Angelo G L, McQueen C A

出版信息

Proc Natl Acad Sci U S A. 1971 Sep;68(9):2087-91. doi: 10.1073/pnas.68.9.2087.

Abstract

The low tissue concentrations of tetrahydrobiopterin, as well as the antagonism between the catecholamine feedback inhibition of tyrosine hydroxylase and the reduced cofactor concentrations, suggest that dihydropteridine reductase may play an important role in the regulation of catecholamine biosynthesis. The interaction of the different components involved in the hydroxylation of tyrosine was studied in vitro in a complex system composed of tyrosine hydroxylase, dihydropteridine reductase, and the different cofactors. This system has several important characteristics: (a) the rate of dihydroxyphenylalanine formation can be controlled by the concentration of dihydropteridine reductase; (b) low concentrations of catecholamines (2 x 10(-5) M) can produce a marked inhibition of tyrosine hydroxylase activity; and (c) the catecholamine feedback-inhibition of tyrosine hydroxylase can be antagonized by increasing concentrations of dihydropteridine reductase. The properties of the in vitro tyrosine hydroxylase-dihydropteridine reductase system suggest that dihydropteridine reductase may have an important role in vivo in the determination of the rates of dihydroxyphenylalanine formation and on the effectiveness of the catecholamine feedback-inhibition of tyrosine hydroxylase activity.

摘要

四氢生物蝶呤的组织浓度较低,以及儿茶酚胺对酪氨酸羟化酶的反馈抑制与还原型辅因子浓度降低之间的拮抗作用,表明二氢蝶啶还原酶可能在儿茶酚胺生物合成的调节中发挥重要作用。在由酪氨酸羟化酶、二氢蝶啶还原酶和不同辅因子组成的复杂体外系统中,研究了参与酪氨酸羟化的不同成分之间的相互作用。该系统具有几个重要特性:(a)二羟苯丙氨酸的形成速率可由二氢蝶啶还原酶的浓度控制;(b)低浓度的儿茶酚胺(2×10⁻⁵ M)可显著抑制酪氨酸羟化酶活性;(c)增加二氢蝶啶还原酶的浓度可拮抗儿茶酚胺对酪氨酸羟化酶的反馈抑制。体外酪氨酸羟化酶-二氢蝶啶还原酶系统的特性表明,二氢蝶啶还原酶在体内可能在决定二羟苯丙氨酸的形成速率以及儿茶酚胺对酪氨酸羟化酶活性的反馈抑制效果方面发挥重要作用。

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Beef adrenal medulla dihydropteridine reductase.牛肉肾上腺髓质二氢蝶啶还原酶
Biochim Biophys Acta. 1969 Nov 4;191(2):485-7. doi: 10.1016/0005-2744(69)90272-1.

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Inhibitors of purified beef adrenal tyrosine hydroxylase.纯化牛肾上腺酪氨酸羟化酶的抑制剂。
Biochem Pharmacol. 1965 May;14(5):837-45. doi: 10.1016/0006-2952(65)90103-6.

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