Effect of metals and phenylalanine on the activity of human tryptophan hydroxylase-2: Comparison with that on tyrosine hydroxylase activity
Effect of metals and phenylalanine on the activity of human tryptophan hydroxylase-2: Comparison with that on tyrosine hydroxylase activity
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DOI：
10.1016/j.neulet.2006.03.031
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发表时间：
2006-07-03
影响因子：
2.5
通讯作者：
Ichinose, Hiroshi
中科院分区：
文献类型：
--
作者：
Ogawa, Shintaro;Ichinose, Hiroshi
我们利用RT-PCR技术克隆了人色氨酸羟化酶-2(HTPH2)基因，并将其表达纯化为麦芽糖结合蛋白(MBP)融合蛋白。我们首次研究了必需二价阳离子和L-苯丙氨酸(L-苯丙氨酸)对hTPH2活性的影响，并与对人酪氨酸羟化酶(HTH1)活性的影响进行了比较。我们发现钴和锰离子对这两种酶的活性都有抑制作用，但hTH1在较低浓度时受到影响。从动力学分析中我们发现，苯丙氨酸对hTPH2的抑制作用比对hTH1的抑制作用更强。这些数据对于阐明高苯丙氨酸血症和慢性锰中毒等病理生理条件下脑内5-羟色胺和儿茶酚胺含量变化的分子机制具有重要意义。(C)2006爱思唯尔爱尔兰有限公司。保留所有权利。
We cloned the human tryptophan hydroxylase-2 (hTPH2) gene by RT-PCR, and expressed and purified its product as a maltose-binding protein (MBP)-fusion protein. We investigated the effects of essential divalent cations and L-phenylalanine (L-Phe) on the hTPH2 activity for the first time, and compared them with those on human tyrosine hydroxylase (hTH1) activity. We found that cobaltous and manganous ions inhibited the activities of both enzymes but that hTH1 was affected at lower concentrations than hTPH2. From kinetic analyses, we found that phenylalanine acted as an inhibitor more strongly against hTPH2 than against hTH1 These data are important for elucidating the molecular mechanism underlying the alterations in the contents of serotonin and catecholamines in the brain under pathological and physiological conditions, such as hyperphenylalaninemia and chronic manganese toxicity. (c) 2006 Elsevier Ireland Ltd. All rights reserved.