Chronic Immune Stimulation May Cause Moderate Impairment of Phenylalanine 4-hydroxylase

Pteridines ◽  
2011 ◽  
Vol 22 (1) ◽  
pp. 120-125 ◽  
Author(s):  
S Scholl-Bürgi ◽  
S Schroecksnadel ◽  
M Jenny ◽  
D Karall ◽  
D Fuchs
Keyword(s):  
Amino Acid ◽  
Immune Activation ◽  
Clinical Relevance ◽  
Inflammatory Diseases ◽  
Immune Stimulation ◽  
Elevated Plasma ◽  
Chronic Inflammatory Diseases ◽  
Patients With Cancer ◽  
Classical Phenylketonuria ◽  
Hiv 1

Abstract Phenylalanine (4)-hydroxylase (PAH, E.C. 1.14.16.1) is located mainly in liver and converts amino acid phenylalanine (Phe) to tyrosine (Tyr). In 'classical' phenylketonuria (PKU), PAH activity is reduced, whereas in 'atypical' PKU biosynthesis of the cofactor 5,6,7,8-tetrahydrobiopterin (BH4) is disturbed. Aside from these inherited conditions, elevated plasma Phe concentrations and increased Phe to Tyr ratios (Phe/Tyr) were observed in patients with cancer, burns, sepsis and HIV-1 infection. Results indicate that immune activation and inflammation are associated with moderate impairment of PAH activity. This review discusses findings of increased Phe/Tyr in patients suffering from chronic inflammatory diseases, their clinical relevance and consequences.

scholarly journals The biology of ergothioneine, an antioxidant nutraceutical

2020 ◽  
Vol 33 (2) ◽  
pp. 190-217 ◽  
Author(s):  
Irina Borodina ◽  
Louise C. Kenny ◽  
Cathal M. McCarthy ◽  
Kalaivani Paramasivan ◽  
Etheresia Pretorius ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amino Acid ◽  
Antioxidant Activities ◽  
Inflammatory Diseases ◽  
Regulatory Agencies ◽  
Fruiting Bodies ◽  
Solute Carrier Family ◽  
Chronic Inflammatory Diseases ◽  
The Status ◽  
Solute Carrier

AbstractErgothioneine (ERG) is an unusual thio-histidine betaine amino acid that has potent antioxidant activities. It is synthesised by a variety of microbes, especially fungi (including in mushroom fruiting bodies) and actinobacteria, but is not synthesised by plants and animals who acquire it via the soil and their diet, respectively. Animals have evolved a highly selective transporter for it, known as solute carrier family 22, member 4 (SLC22A4) in humans, signifying its importance, and ERG may even have the status of a vitamin. ERG accumulates differentially in various tissues, according to their expression of SLC22A4, favouring those such as erythrocytes that may be subject to oxidative stress. Mushroom or ERG consumption seems to provide significant prevention against oxidative stress in a large variety of systems. ERG seems to have strong cytoprotective status, and its concentration is lowered in a number of chronic inflammatory diseases. It has been passed as safe by regulatory agencies, and may have value as a nutraceutical and antioxidant more generally.

scholarly journals IL-33/regulatory T cell axis triggers the development of a tumor-promoting immune environment in chronic inflammation

2019 ◽  
Vol 116 (7) ◽  
pp. 2646-2651 ◽  
Author(s):  
Amir H. Ameri ◽  
Sara Moradi Tuchayi ◽  
Anniek Zaalberg ◽  
Jong Ho Park ◽  
Kenneth H. Ngo ◽  
...  
Keyword(s):  
T Cell ◽  
Chronic Inflammation ◽  
Regulatory T Cell ◽  
Inflammatory Diseases ◽  
Cell Axis ◽  
Chronic Inflammatory Diseases ◽  
Patients With Cancer ◽  
Risk Patients ◽  
Allergic Contact

Chronic inflammation’s tumor-promoting potential is well-recognized; however, the mechanism underlying the development of this immune environment is unknown. Studying the transition from acute, tumor-suppressive to chronic, tumor-promoting allergic contact dermatitis (ACD) revealed how tumor-promoting chronic inflammation develops. Epidermis-derived interleukin (IL)-33 up-regulation and its induction of regulatory T cell (Treg) accumulation in the skin preceded the transition from acute to chronic ACD and triggered the tumor-promoting immune environment in chronic ACD. Mice lacking IL-33 were protected from chronic ACD and its skin cancer sequela compared with wild-type controls (P= 0.0002). IL-33’s direct signaling onto Tregs was required for the development of the tumor-promoting immune environment in the skin. IL-33–Treg signaling was also required for chronic colitis and its associated colorectal cancer development in a colitis model (P< 0.0001). Significantly increased IL-33 and Tregs marked the perilesional skin and colon in patients with cancer-prone chronic inflammatory diseases. Our findings elucidate the role of the IL-33/Treg axis in creating a tumor-promoting immune environment in chronic inflammatory diseases and suggest therapeutic targets for cancer prevention and treatment in high-risk patients.

scholarly journals Modulation of Phenylalanine and Tyrosine Metabolism in HIV-1 Infected Patients with Neurocognitive Impairment: Results from a Clinical Trial

Metabolites ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 274
Author(s):  
Giuseppe P. Innocenti ◽  
Letizia Santinelli ◽  
Luca Laghi ◽  
Cristian Borrazzo ◽  
Claudia Pinacchio ◽  
...  
Keyword(s):  
Amino Acid ◽  
Immune Activation ◽  
Fecal Sample ◽  
Acid Metabolism ◽  
Proton Nuclear Magnetic Resonance ◽  
Control Group ◽  
Healthy Individuals ◽  
Sample Collection ◽  
Tyrosine Metabolism ◽  
Hiv 1

To investigate the effects of oral bacteriotherapy on intestinal phenylalanine and tyrosine metabolism, in this longitudinal, double-arm trial, 15 virally suppressed HIV+ individuals underwent blood and fecal sample collection at baseline and after 6 months of oral bacteriotherapy. A baseline fecal sample was collected from 15 healthy individuals and served as control group for the baseline levels of fecal phenylalanine and tyrosine. CD4 and CD8 immune activation (CD38+) was evaluated by flow cytometry. Amino acid evaluation on fecal samples was conducted by Proton Nuclear Magnetic Resonance. Results showed that HIV+ participants displayed higher baseline phenylalanine/tyrosine ratio values than healthy volunteers. A significand reduction in phenylalanine/tyrosine ratio and peripheral CD4+ CD38+ activation was observed at the end of oral bacteriotherapy. In conclusion, probiotics beneficially affect the immune activation of HIV+ individuals. Therefore, the restoration of intestinal amino acid metabolism could represent the mechanisms through which probiotics exert these desirable effects.

Chronic Inflammatory Diseases: Progress and Prospect with Herbal Medicine

2015 ◽  
Vol 22 (2) ◽  
pp. 247-264 ◽  
Author(s):  
Nilanjan Ghosh ◽  
Asif Ali ◽  
Rituparna Ghosh ◽  
Shaileyee Das ◽  
Subhash C. Mandal ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Diseases

Exploiting Anti-Inflammation Effects of Flavonoids in Chronic Inflammatory Diseases

2020 ◽  
Vol 26 (22) ◽  
pp. 2610-2619 ◽  
Author(s):  
Tarique Hussain ◽  
Ghulam Murtaza ◽  
Huansheng Yang ◽  
Muhammad S. Kalhoro ◽  
Dildar H. Kalhoro
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Inflammatory Diseases ◽  
Therapeutic Option ◽  
Cellular Level ◽  
Antiinflammatory Drugs ◽  
Suitable Alternative ◽  
Chronic Inflammatory Diseases

Background: Inflammation is a complex response of the host defense system to different internal and external stimuli. It is believed that persistent inflammation may lead to chronic inflammatory diseases such as, inflammatory bowel disease, neurological and cardiovascular diseases. Oxidative stress is the main factor responsible for the augmentation of inflammation via various molecular pathways. Therefore, alleviating oxidative stress is effective a therapeutic option against chronic inflammatory diseases. Methods: This review article extends the knowledge of the regulatory mechanisms of flavonoids targeting inflammatory pathways in chronic diseases, which would be the best approach for the development of suitable therapeutic agents against chronic diseases. Results: Since the inflammatory response is initiated by numerous signaling molecules like NF-κB, MAPK, and Arachidonic acid pathways, their encountering function can be evaluated with the activation of Nrf2 pathway, a promising approach to inhibit/prevent chronic inflammatory diseases by flavonoids. Over the last few decades, flavonoids drew much attention as a potent alternative therapeutic agent. Recent clinical evidence has shown significant impacts of flavonoids on chronic diseases in different in-vivo and in-vitro models. Conclusion: Flavonoid compounds can interact with chronic inflammatory diseases at the cellular level and modulate the response of protein pathways. A promising approach is needed to overlook suitable alternative compounds providing more therapeutic efficacy and exerting fewer side effects than commercially available antiinflammatory drugs.

scholarly journals Amino-Acid Co-Variation in HIV-1 Gag Subtype C: HLA-Mediated Selection Pressure and Compensatory Dynamics

PLoS ONE ◽  
2010 ◽  
Vol 5 (9) ◽  
pp. e12463 ◽  
Author(s):  
Morgane Rolland ◽  
Jonathan M. Carlson ◽  
Siriphan Manocheewa ◽  
J. Victor Swain ◽  
Erinn Lanxon-Cookson ◽  
...  
Keyword(s):  
Amino Acid ◽  
Selection Pressure ◽  
Subtype C ◽  
Hiv 1

scholarly journals Specificity of the HIV-1 Protease on Substrates Representing the Cleavage Site in the Proximal Zinc-Finger of HIV-1 Nucleocapsid Protein

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1092
Author(s):  
János András Mótyán ◽  
Márió Miczi ◽  
Stephen Oroszlan ◽  
József Tőzsér
Keyword(s):  
Amino Acid ◽  
Zinc Finger ◽  
Cleavage Site ◽  
Potential Role ◽  
Binding Mode ◽  
Interaction Energies ◽  
Vitro Assay ◽  
Hiv 1

To explore the sequence context-dependent nature of the human immunodeficiency virus type 1 (HIV-1) protease’s specificity and to provide a rationale for viral mutagenesis to study the potential role of the nucleocapsid (NC) processing in HIV-1 replication, synthetic oligopeptide substrates representing the wild-type and modified versions of the proximal cleavage site of HIV-1 NC were assayed as substrates of the HIV-1 protease (PR). The S1′ substrate binding site of HIV-1 PR was studied by an in vitro assay using KIVKCF↓NCGK decapeptides having amino acid substitutions of N17 residue of the cleavage site of the first zinc-finger domain, and in silico calculations were also performed to investigate amino acid preferences of S1′ site. Second site substitutions have also been designed to produce “revertant” substrates and convert a non-hydrolysable sequence (having glycine in place of N17) to a substrate. The specificity constants obtained for peptides containing non-charged P1′ substitutions correlated well with the residue volume, while the correlation with the calculated interaction energies showed the importance of hydrophobicity: interaction energies with polar residues were related to substantially lower specificity constants. Cleavable “revertants” showed one residue shift of cleavage position due to an alternative productive binding mode, and surprisingly, a double cleavage of a substrate was also observed. The results revealed the importance of alternative binding possibilities of substrates into the HIV-1 PR. The introduction of the “revertant” mutations into infectious virus clones may provide further insights into the potential role of NC processing in the early phase of the viral life-cycle.

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