Control Mechanism of the Formation of Neurotransmitter Monoamines by Pteridine Cofactor.

四氢生物蝶呤（Tetrahydrobiopterin，BH_4）是芳香族氨基酸羟化酶（如酪氨酸羟化酶和色氨酸羟化酶）的重要辅因子，是生物合成儿茶酚胺和吲哚胺的限速酶。因此，组织中BH_4浓度的变化有效地控制了单胺的生成。（1）大鼠唾液腺的某些分泌功能受交感神经系统的调节。用高效液相色谱法测定唾液腺中BH_4的含量。一个明显恒定的生物蝶呤浓度观察到在腺体中，在成熟后的时期内，在交感神经支配的腺体和儿茶酚胺的浓度表现相似。（2）Ret肝具有较高的黑胡椒素还原酶（sepiapterin reductase，SPR）活性，SPR是参与BH_4生物合成途径的最后一步的酶。这种激素刺激在注射后最大震颤的时间上与需要BH_4作为辅助因子的肝苯丙氨酸羟化酶的刺激非常相似。（3）SPR在BH_4生物合成过程中对酮基化合物的中间产物起NADPH氧化还原酶的作用。此外，SPR还具有催化6-乳酰四氢蝶呤（C1 ′-ketoPH_4）转化为6- 1 ′-羟基-2 ′-氧代丙基四氢蝶呤（C2 ′-ketoPH_4）的”异构酶活性”。还发现少量NADP+或NADPH可刺激新的活性。我们推测SPR还原异戊酰四氢蝶呤生成BH_4的顺序反应中包括了该异构化反应，即，异戊酰基四氢蝶呤->[C1 '-酮基PH_4 -> C2'-酮基PH_4] -> BH_4。（4）综述了BH_4在动物体内的生物合成及其最后一步反应机理。

Tetrahydrobiopterin (BH_4) is an essential cofactor of aromatic amino acid hydroxylases such as tyrosine hydroxylase and tryptophan hydroxylase which are rate-limiting enzymes in the biosyntheses of catecholamine and indolamine. Thus the change in the concetration of BH_4 in the tissue effectively controls the formation of monoamines. (1)Some secretory functions of the rat salivary gland are regulated by the sympathetic nervous system. BH_4 in salivary glands of rate were meaured by HPLC method. An apparently constant biopterin concentration was observed in the gland, during the period after maturation in sympathetic innervation of the gland and the concentration of catecholamines behaved similarly. (2)Ret liver has quite high activity of sepiapterin reductase (SPR) which is an enzyme involved in the last step of the biosynthetic pathway of BH_4.SPR activity in rat liver was transiently stimulated by the injection of glucagon. This hormonal stimulation was quite similar, in time of maximal strimulation after injection, to that of hepatic phenylalanine hydroxylase which requires BH_4 as a confactor. (3)SPR acts as a NADPH-oxidoreductase against intermediates of keto-comound in BH_4 biosynthesis to form BH_4. Besides this activity, we found that SPR has an" isomerase activity" catalyzing the conversion of 6-lactoyl tetrahydropterin (Cl'-keto PH_4) into 6-1'-hydroxy-2'-oxopropyl tetrahydropterin (C2'-keto PH_4) which are both monoketo intermediates in the biosynthetic pathway of BH_4. It was also found that the new activity was stimulated by a small amount of NADP+ or NADPH. We postulated that reduction of pyruvoyl tetrahydropterin to BH_4 by SPR involves this isomerizing reaction in its sequential reaction; i.e., pyruvoyl tetrahydropterin ->[Cl'-keto PH_4 -> C2'-keto PH_4] -> BH_4. (4)Biosynthesis of BH_4 in animals or in reaction mechanism of its last step was summarized in our revies.