Gostner Johanna M, Becker Kathrin, Kurz Katharina, Fuchs Dietmar
Division of Medical Biochemistry, Biocenter, Medical University of Innsbruck , Innsbruck , Austria.
Division of Biological Chemistry, Biocenter, Medical University of Innsbruck , Innsbruck , Austria.
Front Psychiatry. 2015 Jul 14;6:97. doi: 10.3389/fpsyt.2015.00097. eCollection 2015.
Blood levels of the amino acid phenylalanine, as well as of the tryptophan breakdown product kynurenine, are found to be elevated in human immunodeficiency virus type 1 (HIV-1)-infected patients. Both essential amino acids, tryptophan and phenylalanine, are important precursor molecules for neurotransmitter biosynthesis. Thus, dysregulated amino acid metabolism may be related to disease-associated neuropsychiatric symptoms, such as development of depression, fatigue, and cognitive impairment. Increased phenylalanine/tyrosine and kynurenine/tryptophan ratios are associated with immune activation in patients with HIV-1 infection and decrease upon effective antiretroviral therapy. Recent large-scale metabolic studies have confirmed the crucial involvement of tryptophan and phenylalanine metabolism in HIV-associated disease. Herein, we summarize the current status of the role of tryptophan and phenylalanine metabolism in HIV disease and discuss how inflammatory stress-associated dysregulation of amino acid metabolism may be part of the pathophysiology of common HIV-associated neuropsychiatric conditions.
在1型人类免疫缺陷病毒（HIV-1）感染患者中，发现血液中的氨基酸苯丙氨酸以及色氨酸分解产物犬尿氨酸水平升高。色氨酸和苯丙氨酸这两种必需氨基酸都是神经递质生物合成的重要前体分子。因此，氨基酸代谢失调可能与疾病相关的神经精神症状有关，如抑郁、疲劳和认知障碍的发展。苯丙氨酸/酪氨酸和犬尿氨酸/色氨酸比值升高与HIV-1感染患者的免疫激活有关，而在有效的抗逆转录病毒治疗后会降低。最近的大规模代谢研究证实了色氨酸和苯丙氨酸代谢在HIV相关疾病中的关键作用。在此，我们总结了色氨酸和苯丙氨酸代谢在HIV疾病中的作用现状，并讨论了与炎症应激相关的氨基酸代谢失调如何可能成为常见HIV相关神经精神疾病病理生理学的一部分。
