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

四氢生物蝶呤(BH4)是酪氨酸羟基酶和色氨酸羟基酶等芳香族氨基酸羟基酶的重要辅因子，它们是儿茶酚胺和吲哚胺生物合成的限速酶。因此，组织中BH_4浓度的变化有效地控制了单胺的形成。(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大鼠唾液腺中的BH4含量。在腺体交感神经支配的成熟期，腺体内的生物蝶呤浓度明显恒定，儿茶酚胺的浓度也有类似的变化。(2)大鼠肝脏具有较高的海燕蝶呤还原酶(SPR)活性，该酶参与BH_4生物合成途径的最后一步。在注射后的最大震颤时间，这种激素刺激与需要BH_4作为因子的肝脏苯丙氨酸羟基酶的刺激非常相似。(3)SPR在BH_4生物合成中起着NADPH-氧化还原酶的作用，阻止BH_4生物合成中的酮基中间体生成BH_4。此外，我们还发现SPR具有催化6-乳基四氢蝶呤(CL‘-keto PH_4)转化为6-1’-羟基-2‘-氧丙基四氢蝶呤(C2’-keto PH_4)的“异构酶活性”，这两种产物都是BH_4生物合成途径中的单酮中间体。我们推测，SPR将丙酮酰四氢蝶呤还原为BH_4，在其顺序反应中涉及这种异构化反应，即丙酮酰四氢蝶呤-&gt；[Cl‘-keto PH_4-&gt；C2’-keto PH_4]-&gt；BH_4。(4)综述了BH_4的动物生物合成或其最后一步的反应机理。

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.