Wirleitner B, Neurauter G, Schröcksnadel K, Frick B, Fuchs D
Institute of Medical Chemistry and Biochemistry, University of Innsbruck, and Ludwig Boltzmann Institute of AIDS Research, Fritz-Pregl-Strasse 3, A-6020 Innsbruck, Austria.
Curr Med Chem. 2003 Aug;10(16):1581-91. doi: 10.2174/0929867033457179.
Tryptophan is an essential amino acid and the least abundant constituent of proteins. In parallel it represents a source for two important biochemical pathways: the generation of neurotransmitter 5-hydroxytryptamine (serotonin) by the tetrahydrobiopterin-dependent tryptophan 5-hydroxylase, and the formation of kynurenine derivatives and nicotinamide adenine dinucleotides initiated by the enzymes tryptophan pyrrolase (tryptophan 2,3-dioxygenase, TDO) and indoleamine 2,3-dioxygenase (IDO). Whereas TDO is located in the liver cells, IDO is expressed in a large variety of cells and is inducible by the cytokine interferon-gamma. Therefore, accelerated tryptophan degradation is observed in diseases and disorders concomitant with cellular immune activation, e. g. infectious, autoimmune, and malignant diseases, as well as during pregnancy. According to the cytostatic and antiproliferative properties of tryptophan-depletion on T lymphocytes, activated T-helper type 1 (Th-1) cells may down-regulate immune response via degradation of tryptophan. Especially in states of persistent immune activation availability of free serum tryptophan is diminished and as a consequence of reduced serotonin production, serotonergic functions may as well be affected. Accumulation of neuroactive kynurenine metabolites such as quinolinic acid may contribute to the development of neurologic/psychiatric disorders. Thus, IDO seems to represent a link between the immunological network and neuroendocrine functions with far reaching consequences in regard to the psychological status of patients. These observations provide a basis for the better understanding of mood disorder and related symptoms in chronic diseases.
色氨酸是一种必需氨基酸，也是蛋白质中含量最少的成分。同时，它是两条重要生化途径的来源：由四氢生物蝶呤依赖性色氨酸5-羟化酶生成神经递质5-羟色胺（血清素），以及由色氨酸吡咯酶（色氨酸2,3-双加氧酶，TDO）和吲哚胺2,3-双加氧酶（IDO）启动生成犬尿氨酸衍生物和烟酰胺腺嘌呤二核苷酸。TDO位于肝细胞中，而IDO在多种细胞中表达，并且可被细胞因子γ干扰素诱导。因此，在与细胞免疫激活相关的疾病和病症中，例如感染性、自身免疫性和恶性疾病以及妊娠期间，观察到色氨酸降解加速。根据色氨酸耗竭对T淋巴细胞的细胞抑制和抗增殖特性，活化的1型辅助性T细胞（Th-1）可能通过色氨酸降解下调免疫反应。特别是在持续免疫激活状态下，游离血清色氨酸的可用性降低，并且由于血清素产生减少，血清素能功能也可能受到影响。神经活性犬尿氨酸代谢产物如喹啉酸的积累可能导致神经/精神疾病的发展。因此，IDO似乎代表了免疫网络与神经内分泌功能之间的联系，对患者的心理状态具有深远影响。这些观察结果为更好地理解慢性病中的情绪障碍及相关症状提供了基础。
