Increased blood phenylalanine to tyrosine ratio in HIV-1 infection and correction following effective antiretroviral therapy

Zangerle, Robert; Kurz, Katharina; Neurauter, Gabriele; Kitchen, Maria; Sarcletti, Mario; Fuchs, Dietmar

doi:10.1016/j.bbi.2009.11.004

Cited by 76 publications

(73 citation statements)

References 43 publications

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“…Dysregulation of Tyrosine metabolism has been reported with age and arthritic conditions3839. Involvement of these pathways in different infections like HIV has been previously reported4041. Interestingly Pyrimidine metabolism is also affected during the co-infection which could possibly affect the nucleic acid synthesis and affect cell cycle.…”

Section: Discussionmentioning

confidence: 93%

Serum metabolomics analysis of patients with chikungunya and dengue mono/co-infections reveals distinct metabolite signatures in the three disease conditions

Shrinet

Shastri

Gaind

et al. 2016

Sci Rep

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Chikungunya and dengue are arboviral infections with overlapping clinical symptoms. A subset of chikungunya infection occurs also as co-infections with dengue, resulting in complications during diagnosis and patient management. The present study was undertaken to identify the global metabolome of patient sera infected with chikungunya as mono infections and with dengue as co-infections. Using nuclear magnetic resonance (NMR) spectroscopy, the metabolome of sera of three disease conditions, namely, chikungunya and dengue as mono-infections and when co-infected were ascertained and compared with healthy individuals. Further, the cohorts were analyzed on the basis of age, onset of fever and joint involvement. Here we show that many metabolites in the serum are significantly differentially regulated during chikungunya mono-infection as well as during chikungunya co-infection with dengue. We observed that glycine, serine, threonine, galactose and pyrimidine metabolisms are the most perturbed pathways in both mono and co-infection conditions. The affected pathways in our study correlate well with the clinical manifestation like fever, inflammation, energy deprivation and joint pain during the infections. These results may serve as a starting point for validations and identification of distinct biomolecules that could be exploited as biomarker candidates thereby helping in better patient management.

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Section: Discussionmentioning

confidence: 93%

Serum metabolomics analysis of patients with chikungunya and dengue mono/co-infections reveals distinct metabolite signatures in the three disease conditions

Shrinet

Shastri

Gaind

et al. 2016

Sci Rep

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“…Further regulatory mechanisms of PAH activity with physiological relevance are the binding of phospholipids (e.g., lysolecithin) [39], modification of Cys-237 [40,41], possibly oxidative stress [42,43], as well as several mutations in the protein [44].…”

Section: Allosteric Regulation Of Pahmentioning

confidence: 99%

Dynamic regulation of phenylalanine hydroxylase

Fuchs¹,

Fuchs²,

Liedl

2014

Pteridines

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Phenylalanine hydroxylase (PAH) is the key enzyme in phenylalanine metabolism, catalyzing its oxidative breakdown to tyrosine. Its function in the committed step of amino acid metabolism requires strict regulation. Thus, several regulatory mechanisms are central for an understanding of PAH at the atomistic level. The enzyme is activated by incubation with phenylalanine and inhibited by tetrahydrobiopterin binding. Furthermore, phosphorylation of Ser-16 in the regulatory domain influences enzyme turnover. All major regulatory processes in PAH are connected to the conformational changes within a protein and its oligomeric assembly. The underlying dynamic processes in the enzyme are tackled by a variety of experimental and computational approaches. We especially emphasize the computational approaches, aiming to unravel the changes in the molecular dynamics of PAH that govern allosteric regulation. State-of-the-art molecular dynamics simulations provide access to the conformational transitions in biological macromolecules at the microsecond time scale and beyond. Thus, in silico strategies are promising for the identification of the complex allosteric mechanisms governing PAH activity in vivo.

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“…In addition, a moderate form of hyperphenylalaninaemia is reported for patients who suffer from chronic inflammatory diseases. Notably, in such patients the increased PHE and PHE/TYR concentrations were also found to correlate with neopterin levels [17][18][19].…”

Section: Introductionmentioning

confidence: 95%

Serum tryptophan, kynurenine, phenylalanine, tyrosine and neopterin concentrations in 100 healthy blood donors

Geisler

Mayersbach²,

Becker

et al. 2015

Pteridines

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AbstractFormation of neopterin, a biomarker of the activated human immune system, is linked with tryptophan (TRP) and phenylalanine (PHE) metabolism. To obtain normal values, in this study, serum concentrations of neopterin as well as of TRP, PHE and their respective metabolites kynurenine (KYN) and tyrosine (TYR) were investigated in 100 successive blood donor serum specimens from the University Clinics of Innsbruck, Austria. In addition, nitrite concentrations were determined. Donors had passed anamnestic examination at entry and were therefore considered as healthy. The mean age of participants was 49±11.4 (mean±SD) years; 18% were older than 60 years. Both genders were included in the analysis. Neopterin concentrations measured by enzyme-linked immunosorbent assay were 5.9±1.6 nmol/L (mean±SD). Levels of amino acids and metabolites were determined by HPLC. Mean KYN and TRP concentrations were 1.78±0.42 μmol/L and 67.4±10.2 μmol/L, respectively. KYN to TRP ratio (KYN/TRP), an estimate for the activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase, was 26.7±6.2 μmol/mmol. Mean PHE and TYR concentrations were 65.2±11.1 μmol/L and 90.6±22.9 μmol/L. PHE to TYR ratio (PHE/TYR), an estimate for the activity of PHE-converting enzyme phenylalanine hydroxylase, was 0.75±0.14 μmol/μmol. Nitrite concentrations, estimated by Griess-Ilosvay reagent, were 44.9±32.0 μmol/L. Males were taller and heavier than females (both p<0.01), but body mass index did not differ. Males presented with significantly higher TRP and TYR concentrations than females (both p<0.05). There existed significant correlations between neopterin and KYN (rs=0.368), KYN/TRP (rs=0.453), TYR (rs=–0.267; all p<0.01) and PHE/TYR (rs=0.236; p<0.05) concentrations. Data indicate that also in a population of healthy individuals an association exists between “low-grade” immune activation as is indicated by slightly higher neopterin concentrations and biochemical alterations in the amino acid metabolism. Although minor, such changes may interfere with psychoneuroimmunological regulatory networks and thus be of clinical relevance.

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Increased blood phenylalanine to tyrosine ratio in HIV-1 infection and correction following effective antiretroviral therapy

Cited by 76 publications

References 43 publications

Serum metabolomics analysis of patients with chikungunya and dengue mono/co-infections reveals distinct metabolite signatures in the three disease conditions

Serum metabolomics analysis of patients with chikungunya and dengue mono/co-infections reveals distinct metabolite signatures in the three disease conditions

Dynamic regulation of phenylalanine hydroxylase

Serum tryptophan, kynurenine, phenylalanine, tyrosine and neopterin concentrations in 100 healthy blood donors

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