Okuno S, Fujisawa H
Department of Biochemistry, Asahikawa Medical College, Japan.
J Neurochem. 1991 Jul;57(1):53-60. doi: 10.1111/j.1471-4159.1991.tb02098.x.
We have reported previously that tyrosine hydroxylase in the crude extract from rat striatum exists in the inactive form showing almost no activity at the physiological pH and that the inactive form is produced by the action of the end products of the enzyme, such as dopamine. The incubation of the enzyme with the end products resulted in not only the inactivation but also a remarkable stabilization of the enzyme. Catechols possessing amino groups but no negatively charged groups on the side chains (catecholamine-type catechols) were effective at a concentration as low as 10(-7) M in both the inactivation and stabilization of the enzyme. In contrast, catechols not possessing positively or negatively charged side chains (3,4-dihydroxyphenylethyleneglycol-type catechols) were ineffective at a concentration of 10(-7) M but effective at a concentration of 10(-6) M for both the inactivation and stabilization. Catechols possessing negatively charged groups (3,4-dihydroxyphenylacetic acid-type catechols) were ineffective even at a concentration of 10(-6) M. Thus, the end products of tyrosine hydroxylase appear to serve to keep the enzyme inactive and stable. The reaction mechanism of the conversion of the enzyme from the active/labile form to the inactive/stable form by dopamine was also investigated.
我们之前报道过，大鼠纹状体粗提物中的酪氨酸羟化酶以无活性形式存在，在生理pH值下几乎没有活性，且这种无活性形式是由该酶的终产物（如多巴胺）作用产生的。将该酶与终产物一起孵育，不仅导致酶失活，还使其显著稳定。在酶的失活和稳定过程中，侧链上带有氨基但无负电荷基团的儿茶酚（儿茶酚胺型儿茶酚）在低至10⁻⁷ M的浓度下就有效。相比之下，侧链不带正电荷或负电荷的儿茶酚（3,4 - 二羟基苯乙二醇型儿茶酚）在10⁻⁷ M浓度下无效，但在10⁻⁶ M浓度下对酶的失活和稳定均有效。带有负电荷基团的儿茶酚（3,4 - 二羟基苯乙酸型儿茶酚）即使在10⁻⁶ M浓度下也无效。因此，酪氨酸羟化酶的终产物似乎起到使酶保持无活性和稳定的作用。我们还研究了多巴胺将该酶从活性/不稳定形式转化为无活性/稳定形式的反应机制。
