多巴胺类似物抑制二氢蝶啶还原酶的研究

多巴胺类似物对二氢蝶啶还原酶有明显的非竞争性抑制作用(Ki或I_(50)值为10~(-5)—10~(-6)mol/L)。其中阿朴吗啡是最强的抑制剂之一(Ki或I~(50)=1-2×10~(-6)mol/L)。由于酪氨酸羟化酶和二氢蝶啶还原酶包含于同一酶促反应过程中,且限制了多巴胺合成的决定速度的那一步。这些结果可能提示出被多巴胺抑制的酪氨酸羟化作用包含着对这二种酶的抑制作用。

Inhibition of Dihydropteridine Reductase by Dopamine Analogs

This study reports that dopamine (DA)analogs are all potent noncompetitive inhibitors of DHPR from human liver and rat striatal P2-synaptosomes (Ki or I50 values of 10-5 to 10-6mol/L). Apomorphine was the most powerful inhibitor tested (Ki or I50 = 1 - 2 × 10-6mol/L). Dopamine analogs are known competitive inhibitors of tyrosine hydroxylase(TH). Since both TH and DHPR are involved in the hydrox-ylation reaction, which is the rate-limiting step in DA synthesis, these results imply that the feed-back inhibition of tyrosine hydroxylation by DA may involve inhibition of both TH and DHPR.