title: Disturbed Amino Acid Metabolism in HIV: Association with Neuropsychiatric Symptoms.
abstract: 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.
authors.affiliation: Division of Medical Biochemistry, Biocenter, Medical University of Innsbruck , Innsbruck , Austria.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Gostner
authors.affiliation: Division of Biological Chemistry, Biocenter, Medical University of Innsbruck , Innsbruck , Austria.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Becker
authors.affiliation: Department of Internal Medicine VI, Medical University of Innsbruck , Innsbruck , Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Kurz
authors.affiliation: Division of Biological Chemistry, Biocenter, Medical University of Innsbruck , Innsbruck , Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
keywords: HIV; indoleamine 2,3-dioxygenase; kynurenine; phenylalanine; phenylalanine 4-hydroxylase; tetrahydrobiopterin; tryptophan; tyrosine