- 作者：Robert Zangerle ; Katharina Kurz ; Gabriele Neurauter ; Maria Kitchen ; Mario Sarcletti ; Dietmar Fuchs
- 关键词：Phenylalanine ; Tyrosine ; Phenylalanine-hydroxylase ; Oxidative stress ; Immune activation ; Neopterin
- 刊名：Brain, Behavior, and Immunity
- 出版年：2010
- 出版时间：March 2010
- 年：2010
- 卷：24
- 期：3
- 页码：403-408
- 全文大小：281 K
ObjectiveHigher blood levels of the essential amino acid phenylalanine (phe) have been documented in patients with HIV-1 infection. They may relate to a diminished conversion of phe to tyrosine (tyr) by the enzyme phenylalanine-hydroxylase (PAH). PAH is rate-limiting in the biosynthesis of dopamine, and impaired PAH activity is reflected by an increased phe to tyr ratio (phe/tyr).Methods
Plasma phe/tyr was measured in 107 patients with HIV-1 infection before and after 12 months of effective antiretroviral therapy (ART). Results were compared with CD4+ cell counts, HIV-1 RNA levels and concentrations of immune activation marker neopterin.
Results
Before ART, phe/tyr was mean ± S.D.: 0.99 ± 0.57 μmol/μmol. Phe/tyr correlated significantly with plasma and urine neopterin concentrations (rs = 0.434, and rs = 0.392; both p < 0.001) and less strongly with HIV-RNA levels (rs = 0.173) and CD4+ counts (rs = −0.182, both p < 0.05). After ART, phe/tyr dropped to 0.72 ± 0.16 (=−27 % ; U = 5.21, p = 0.01) which was due to an average decline of −14 % of phe concentrations from 73.1 ± 34.0 μmol/L at baseline to 62.9 ± 17.8 μmol/L after ART (U = 2.51, p = 0.01) and a concomitant increase of tyr concentrations (+13 % , U = 2.46, p = 0.01). In parallel, significant reductions of plasma and urine neopterin concentrations were observed during ART.
Conclusions
Increased phe/tyr is frequent in patients with HIV-1 infection and is related to immune activation. ART was found to decrease phe/tyr and this change could indicate and influence on PAH activity. Future studies might be able to show whether the decline of phe/tyr under ART may concur with the often improved neuropsychiatric status in treated patients.