甲状腺激素非脱碘代谢

（七）甲状腺激素非脱碘代谢

甲状腺激素的非脱碘代谢还包括结合、丙氨酸侧链的脱氨脱羧和醚键断裂。

1.结合：结合是指甲状腺激素外环上的酚羟基与某些也带有羟基的化学物质之间发生脱水缩合反应。化学物质主要为硫酸和葡萄糖醛酸，前者与甲状腺的结合称为硫酸化，后者称为葡萄糖醛酸化。硫酸化是由硫酸转移酶（SULT）催化，分为SULT-1、SULT-2、SULT-3。其中SULT-1催化酚类物质，甲状腺激素属于酚类化合物，所以SULT-1又叫作酚硫酸转移酶。SULT-1位于细胞质，由两个亚基构成，每个亚单位分子量为34 000。硫酸化对甲状腺激素脱碘代谢具有重要影响，硫酸化会增加D1催化的甲状腺激素内环脱碘，硫酸化T4的内环脱碘能力较未硫酸化的T4增强200倍。硫酸化的甲状腺激素可以通过去硫酸化过程回到非硫酸化状态，由芳基硫酸酶催化，因此硫酸化甲状腺激素可作为甲状腺激素的储库。

葡萄糖醛酸化是碘甲状腺原氨酸外环与葡萄糖醛酸的缩合反应。葡萄糖醛酸需要活化成二磷酸葡萄糖醛酸才能参加反应。甲状腺激素的葡萄糖醛酸化主要发生在肝脏。肝脏形成的葡萄糖醛酸化碘甲状腺原氨酸随胆汁排入肠道，肠道厌氧菌产生的β-葡萄糖醛酸酶可催化葡萄糖醛酸化碘甲状腺原氨酸水解，使碘甲状腺原氨酸重新游离出来。葡萄糖醛酸化需要在尿苷二磷酸葡萄糖醛酸基转移酶（UGT）作用下发生，UGT属于肝微粒体酶，因而影响肝微粒体酶的药物会对甲状腺的葡萄糖醛酸化有一定影响。

2.丙氨酸侧链的脱氨脱羧 ：丙氨酸侧链的脱氨是由甲状腺氨基转移酶催化，脱羧反应是由L-氨基酸氧化酶催化。甲状腺激素的脱羧脱氨产物为乙酸衍生物碘甲腺乙酸，这些产物可以继续进行其他代谢。T3脱羧脱氨产物为TRIAC，T4脱羧脱氨产物为TETRAC；TRIAC和TETRAC都有甲状腺激素活性，TRIAC抑制TSH分泌的作用很强，TRIAC的特点具有临床意义，在治疗甲状腺激素抵抗或甲状腺癌时，可以有效抑制TSH的同时而不会带来外周甲亢的副作用。

3.醚键断裂：在过氧化物酶的作用下，甲状腺激素的外环和内环之间的醚键会发生氧化断裂。T4的醚键断裂后内环形成DIT，随后这些DIT进入血液循环，外环部分会迅速脱碘，形成不稳定的醌。

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