Metabolism of Thyroid Hormones, Enphasizing the Enzymes which Catalyze the Deamination of their Alanine Side Chain

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  • NAKANO Minoru
    Department of Biochemistry, School of Medicine, Gunma University,Japan

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  • 2.甲状腺ホルモンの代謝特に脱アミノを触媒する酵素について
  • 甲状腺ホルモンの代謝 特に脱アミノを触媒する酵素について
  • コウジョウセン ホルモン ノ タイシャ トクニ ダツアミノ オ ショクバイ スル コウソ ニ ツイテ

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Biochemical transformation of the thyroid hormone molecules in the mammalian tissue can occur at various points on the molecule. This is summarized as follows : (1) deiodination; (2) conjugation of glucuronic acid; (3) decarboxylation; and (4) deamination of the alanine side chain.<BR>In our laboratories, the enzymes catalyzing reaction (4), oxidase and transaminase, have been purified from rat kidney.<BR>The oxidase was obtained in crystal form from rat kidney mitochondria and soluble fractions and found to have 6 moles of FMN per mole of the enzyme (Molecular weight, 310,000). The enzyme catalyzes the oxidation of many α-amino monocarboxylic acids and α-hydroxy acids (L-configuration) including thyroid hormones. In recent study concerning intracellular distribution of the oxidase by sucrose density gradient centrifugation, the oxidase was found to be mainly located in microbodies (peroxisomes) rather than mitochondria.<BR>The transaminase has been purified 30 fold from rat kidney mitochondrial extract. The enzyme requires pyridoxal-5'-phosphate as coenzyme and α-ketoglutarate as amino acceptor. The transaminase is highly specific for thyroid hormones and halogenated tyrosines. In contrast to tyrosine-α-ketoglutarate transaminase, this enzyme was not induced in vivo by hydrocortisone.<BR>The pyruvic acid analogues of thyroid hormones have not been detected as product of the above transamination and oxidative deamination, while the corresponding acetic acid analogues were accumulated in the same condition. This may be attributable to the instability of the pyruvic acid analogues in alkaline media and chromatography in alkaline solvent systems.<BR>On the basis of the fact that in the presence of aromatic α-keto acid reductase and NADH the main product of the deamination reactions is the lactic acid analogues of thyroid hormones, it can be concluded that the product of the first stage of the enzymatic deamination is the pyruvic acid analogues. Aromatic α-keto acid reductase is widely distributed in rat tissues and other animal tissues. This enzyme, purified from rat kidney; is highly specific for the aromatic keto acids corresponding to thyroid hormones and halogenated tyrosines.<BR>Routes for side chain degradation of thyroid hormone (T3, or T4) are depicted as follows : <BR>T3 Oxidase Pyruvic acid analogue Transaminases NAD NADH+H+Lactic acid analogues Aromatic α-keto acid reductase Acetic acid analogues

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