Smith G K
Arch Biochem Biophys. 1987 Jun;255(2):254-66. doi: 10.1016/0003-9861(87)90392-4.
Rat erythrocyte sepiapterin reductase can catalyze the NADPH-dependent reduction of tetrahydropterin substrates with relative velocities of sepiapterin greater than lactoyltetrahydropterin greater than or equal to pyruvoyltetrahydropterin greater than 1'-hydroxy-2'-oxopropyltetrahydropterin; L-erythrotetrahydrobiopterin is the product of the reduction of all three tetrahydropterins. The 1' position of the 1',2'-diketone, pyruvoyltetrahydropterin, is reduced first; the product of this first reduction is 1'-hydroxy-2'-oxopropyltetrahydropterin. Both steps are inhibited by N-acetylserotonin. An antibody to sepiapterin reductase purified from rat erythrocytes was produced in rabbits, and the purified antibody is highly specific for sepiapterin reductase. This antibody is an inhibitor of both sepiapterin reductase activity and tetrahydrobiopterin biosynthesis in crude extracts of rat adrenal and brain. The antibody inhibits the production of both the biosynthetic intermediate, 1'-hydroxy-2'-oxopropyltetrahydropterin, and tetrahydrobiopterin. The results indicate that sepiapterin reductase is on the biosynthetic pathway to tetrahydrobiopterin, and catalyzes the complete reduction of pyruvoyltetrahydropterin to tetrahydrobiopterin. In contrast, homogenates of whole rat adrenal also produce large quantities of lactoyltetrahydropterin which suggests that in some tissues this compound may also be an intermediate in tetrahydrobiopterin biosynthesis. The synthesis of lactoyltetrahydropterin is not inhibited by the antibody to sepiapterin reductase and therefore does not appear to be catalyzed by sepiapterin reductase. However, sepiapterin reductase is responsible for the conversion of lactoyltetrahydropterin to tetrahydrobiopterin. The source of sepiapterin in biosynthetic reactions was found to be oxidative decomposition of lactoyltetrahydropterin.
大鼠红细胞蝶呤还原酶能够催化NADPH依赖的四氢蝶呤底物的还原反应，其对蝶酰三谷氨酸的相对反应速度大于乳酰四氢蝶呤大于或等于丙酮酰四氢蝶呤大于1'-羟基-2'-氧代丙基四氢蝶呤；L-赤藓糖型四氢生物蝶呤是所有这三种四氢蝶呤还原反应的产物。丙酮酰四氢蝶呤的1',2'-二酮的1'位首先被还原；这第一步还原反应的产物是1'-羟基-2'-氧代丙基四氢蝶呤。这两个步骤均受到N-乙酰血清素的抑制。用兔制备了针对从大鼠红细胞中纯化的蝶呤还原酶的抗体，纯化后的抗体对蝶呤还原酶具有高度特异性。该抗体是大鼠肾上腺和脑粗提物中蝶呤还原酶活性和四氢生物蝶呤生物合成的抑制剂。该抗体抑制生物合成中间体1'-羟基-2'-氧代丙基四氢蝶呤和四氢生物蝶呤的产生。结果表明，蝶呤还原酶处于四氢生物蝶呤的生物合成途径上，并催化丙酮酰四氢蝶呤完全还原为四氢生物蝶呤。相反，整个大鼠肾上腺的匀浆也产生大量的乳酰四氢蝶呤，这表明在某些组织中，该化合物也可能是四氢生物蝶呤生物合成的中间体。乳酰四氢蝶呤的合成不受蝶呤还原酶抗体的抑制，因此似乎不是由蝶呤还原酶催化的。然而，蝶呤还原酶负责将乳酰四氢蝶呤转化为四氢生物蝶呤。发现生物合成反应中蝶酰三谷氨酸的来源是乳酰四氢蝶呤的氧化分解。
