-
Pharmacology, Biochemistry, and Behavior Jun 2015The amino acid tyrosine is the precursor to the catecholamine neurotransmitters dopamine and norepinephrine. Increasing tyrosine uptake may positively influence... (Review)
Review
The amino acid tyrosine is the precursor to the catecholamine neurotransmitters dopamine and norepinephrine. Increasing tyrosine uptake may positively influence catecholamine-related psychological functioning. We conducted a systematic review to examine the effects of tyrosine on behavior and cognition. Fifteen studies were reviewed. All studies except one involved tyrosine loading during a single test session. In most behavioral studies, there were no significant effects of tyrosine on exercise performance. In contrast, cognitive studies employing neuropsychological measures found that tyrosine loading acutely counteracts decrements in working memory and information processing that are induced by demanding situational conditions such as extreme weather or cognitive load. The buffering effects of tyrosine on cognition may be explained by tyrosine's ability to neutralize depleted brain catecholamine levels. There is evidence that tyrosine may benefit healthy individuals exposed to demanding situational conditions. For future research we recommend moving from studying the acute effects of a single tyrosine load in small samples to studying the behavioral and cognitive effects of tyrosine in larger groups over multiple weeks.
Topics: Brain; Cognition; Emotions; Exercise Test; Humans; Norepinephrine; Tyrosine
PubMed: 25797188
DOI: 10.1016/j.pbb.2015.03.008 -
Free Radical Research Apr 2015Protein oxidation is increasingly recognised as an important modulator of biochemical pathways controlling both physiological and pathological processes. While much... (Review)
Review
Protein oxidation is increasingly recognised as an important modulator of biochemical pathways controlling both physiological and pathological processes. While much attention has focused on cysteine modifications in reversible redox signalling, there is increasing evidence that other protein residues are oxidised in vivo with impact on cellular homeostasis and redox signalling pathways. A notable example is tyrosine, which can undergo a number of oxidative post-translational modifications to form 3-hydroxy-tyrosine, tyrosine crosslinks, 3-nitrotyrosine and halogenated tyrosine, with different effects on cellular functions. Tyrosine oxidation has been studied extensively in vitro, and this has generated detailed information about the molecular mechanisms that may occur in vivo. An important aspect of studying tyrosine oxidation both in vitro and in biological systems is the ability to monitor the formation of oxidised derivatives, which depends on a variety of analytical techniques. While antibody-dependent techniques such as ELISAs are commonly used, these have limitations, and more specific assays based on spectroscopic or spectrometric techniques are required to provide information on the exact residues modified and the nature of the modification. These approaches have helped understanding of the consequences of tyrosine oxidation in biological systems, especially its effects on cell signalling and cell dysfunction, linking to roles in disease. There is mounting evidence that tyrosine oxidation processes are important in vivo and can contribute to cellular pathology.
Topics: Oxidation-Reduction; Oxidative Stress; Tyrosine
PubMed: 25812585
DOI: 10.3109/10715762.2015.1007968 -
Biomacromolecules Mar 2022The modulation of reaction kinetics with horseradish peroxidase (HRP)-catalyzed cross-linking of proteins remains a useful strategy to modulate hydrogel formation. Here,...
The modulation of reaction kinetics with horseradish peroxidase (HRP)-catalyzed cross-linking of proteins remains a useful strategy to modulate hydrogel formation. Here, we demonstrate that the presence of positively charged lysines in silk-elastin-like polymers impacts the thermal transition temperature of these proteins, while the location in the primary sequence modulates the reactivity of the tyrosines. The positively charged lysine side chains decreased π-π interactions among the tyrosines and reduced the rate of formation and number of HRP-mediated dityrosine bonds, dependent on the proximity of the charged group to the tyrosine. The results suggest that the location of repulsive charges can be used to tailor the reaction kinetics for enzymatic cross-linking, providing further control of gelation rates for gel formation and the resulting protein-based gel characteristics.
Topics: Cross-Linking Reagents; Elastin; Horseradish Peroxidase; Hydrogels; Silk; Tyrosine
PubMed: 35113522
DOI: 10.1021/acs.biomac.1c01192 -
Applied and Environmental Microbiology Dec 2020Rhizobia are bacteria which can either live as free organisms in the soil or interact with plants of the legume family with, as a result, the formation of root organs...
Rhizobia are bacteria which can either live as free organisms in the soil or interact with plants of the legume family with, as a result, the formation of root organs called nodules in which differentiated endosymbiotic bacteria fix atmospheric nitrogen to the plant's benefit. In both lifestyles, rhizobia are exposed to nitric oxide (NO) which can be perceived as a signaling or toxic molecule. NO can act at the transcriptional level but can also modify proteins by -nitrosylation of cysteine or nitration of tyrosine residues. However, only a few molecular targets of NO have been described in bacteria and none of them have been characterized in rhizobia. Here, we examined tyrosine nitration of proteins induced by NO. We found three tyrosine-nitrated proteins in grown under free-living conditions, in response to an NO donor. Two nitroproteins were identified by mass spectrometry and correspond to flagellins A and B. We showed that one of the nitratable tyrosines is essential to flagellin function in motility. Rhizobia are found as free-living bacteria in the soil or in interaction with plants and are exposed to nitric oxide (NO) in both environments. NO is known to have many effects on animals, plants, and bacteria where only a few molecular targets of NO have been described so far. We identified flagellin A and B by mass spectrometry as tyrosine-nitrated proteins in We also showed that one of the nitratable tyrosines is essential to flagellin function in motility. The results enhanced our understanding of NO effects on rhizobia. Identification of bacterial flagellin nitration opens a new possible role of NO in plant-microbe interactions.
Topics: Flagellin; Nitric Oxide; Nitrosative Stress; Sinorhizobium meliloti; Tyrosine
PubMed: 33067191
DOI: 10.1128/AEM.02210-20 -
Chemical Research in Toxicology Apr 2013Soman forms a stable, covalent bond with tyrosine 411 of human albumin, with tyrosines 257 and 593 in human transferrin, and with tyrosine in many other proteins. The...
Soman forms a stable, covalent bond with tyrosine 411 of human albumin, with tyrosines 257 and 593 in human transferrin, and with tyrosine in many other proteins. The pinacolyl group of soman is retained, suggesting that pinacolyl methylphosphonate bound to tyrosine could generate specific antibodies. Tyrosine in the pentapeptide RYGRK was covalently modified with soman simply by adding soman to the peptide. The phosphonylated-peptide was linked to keyhole limpet hemocyanin, and the conjugate was injected into rabbits. The polyclonal antiserum recognized soman-labeled human albumin, soman-mouse albumin, and soman human transferrin but not nonphosphonylated control proteins. The soman-labeled tyrosines in these proteins are surrounded by different amino acid sequences, suggesting that the polyclonal recognizes soman-tyrosine independent of the amino acid sequence. Antiserum obtained after 4 antigen injections over a period of 18 weeks was tested in a competition ELISA where it had an IC50 of 10(-11) M. The limit of detection on Western blots was 0.01 μg (15 picomoles) of soman-labeled albumin. In conclusion, a high-affinity, polyclonal antibody that specifically recognizes soman adducts on tyrosine in a variety of proteins has been produced. Such an antibody could be useful for identifying secondary targets of soman toxicity.
Topics: Animals; Antibodies; Antigens; Enzyme-Linked Immunosorbent Assay; Hemocyanins; Humans; Mice; Oligopeptides; Rabbits; Soman; Tyrosine
PubMed: 23469927
DOI: 10.1021/tx400027n -
Cardiovascular Research Jul 2007Several pathologies of the cardiovascular system are associated with an augmented production of nitric oxide and/or superoxide-derived oxidants and/or alteration in the... (Review)
Review
Several pathologies of the cardiovascular system are associated with an augmented production of nitric oxide and/or superoxide-derived oxidants and/or alteration in the antioxidant detoxification pathways that lead to nitroxidative stress. One important consequence of these reactive intermediates at the biochemical level is the nitration of protein tyrosines, which is performed through either of two of the relevant nitration pathways that operate in vivo, namely peroxynitrite and heme peroxidase-dependent nitration. Proteins nitrated at tyrosine residues have been detected in several compartments of the cardiovascular system. In this review a selection of nitrated proteins in plasma (fibrinogen, plasmin, Apo-1), vessel wall (Apo-B, cyclooxygenase, prostaglandin synthase, Mn-superoxide dismutase) and myocardium (myofibrillar creatine kinase, alpha-actinin, sarcoplasmic reticulum Ca(2+) ATPase) are analyzed in the context of cardiovascular disease. Nitration of tyrosine can affect protein function, which could directly link nitroxidative stress to the molecular alterations found in disease. While some proteins are inactivated by nitration (e.g. Mn-SOD) others undergo a gain-of-function (e.g. fibrinogen) that can have an ample impact on the pathophysiology of the cardiovascular system. Nitrotyrosine is also emerging as a novel independent marker of cardiovascular disease. Pharmacological strategies directed towards inhibiting protein nitration will assist to shed light on the relevance of this post-translational modification to human cardiovascular pathology.
Topics: Animals; Cardiovascular Diseases; Cardiovascular System; Fibrinogen; Humans; Nitric Oxide; Nitrosation; Signal Transduction; Superoxide Dismutase; Tyrosine
PubMed: 17544386
DOI: 10.1016/j.cardiores.2007.04.024 -
Future Medicinal Chemistry Mar 2019More than 40% of the world's population, across 105 countries, live in malaria endemic areas. It is estimated that about 500 million cases of malaria and half a million...
AIM
More than 40% of the world's population, across 105 countries, live in malaria endemic areas. It is estimated that about 500 million cases of malaria and half a million deaths occur per year.
RESULTS
Herein, we demonstrate the biological activity of indole-3-glyoxyl tyrosine against Plasmodium falciparum, which is the causal agent of the most virulent form of malaria in humans. We developed an efficient synthesis of indole-3-glyoxyl tyrosine derivatives, which were then used as key intermediates in the synthesis of functionalized indole-3-glyoxyl biphenyl tyrosines.
CONCLUSION
In biological testing, the compounds exhibited a parasite growth inhibition of over 85%. A cell viability assay showed low cytotoxicity against human cells, with no significant changes in cell viability, making these compounds potential antimalarials.
Topics: Antimalarials; Hep G2 Cells; Humans; Indoles; Malaria; Malaria, Falciparum; Models, Molecular; Parasitic Sensitivity Tests; Plasmodium falciparum; Tyrosine
PubMed: 30916995
DOI: 10.4155/fmc-2018-0246 -
Science Signaling Oct 2014Ligand binding to the receptor tyrosine kinase fibroblast growth factor (FGF) receptor 1 (FGFR1) causes dimerization and activation by transphosphorylation of tyrosine...
Ligand binding to the receptor tyrosine kinase fibroblast growth factor (FGF) receptor 1 (FGFR1) causes dimerization and activation by transphosphorylation of tyrosine residues in the kinase domain. FGFR1 is ubiquitylated by the E3 ligase NEDD4 (also known as NEDD4-1), which promotes FGFR1 internalization and degradation. Although phosphorylation of FGFR1 is required for NEDD4-dependent endocytosis, NEDD4 directly binds to a nonphosphorylated region of FGFR1. We found that activation of FGFR1 led to activation of c-Src kinase-dependent tyrosine phosphorylation of NEDD4, enhancing the ubiquitin ligase activity of NEDD4. Using mass spectrometry, we identified several FGF-dependent phosphorylated tyrosines in NEDD4, including Tyr(43) in the C2 domain and Tyr(585) in the HECT domain. Mutating these tyrosines to phenylalanine to prevent phosphorylation inhibited FGF-dependent NEDD4 activity and FGFR1 endocytosis and enhanced cell proliferation. Mutating the tyrosines to glutamic acid to mimic phosphorylation enhanced NEDD4 activity. Moreover, the NEDD4 C2 domain bound the HECT domain, and the presence of phosphomimetic mutations inhibited this interaction, suggesting that phosphorylation of NEDD4 relieves an inhibitory intra- or intermolecular interaction. Accordingly, activation of FGFR1 was not required for activation of NEDD4 that lacked its C2 domain. Activation of c-Src by epidermal growth factor (EGF) also promoted tyrosine phosphorylation and enhanced the activity of NEDD4. Thus, we identified a feedback mechanism by which receptor tyrosine kinases promote catalytic activation of NEDD4 and that may represent a mechanism of receptor crosstalk.
Topics: DNA, Complementary; Endocytosis; Endosomal Sorting Complexes Required for Transport; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Gene Knockdown Techniques; HeLa Cells; Humans; Immunoprecipitation; Models, Molecular; Mutagenesis, Site-Directed; Nedd4 Ubiquitin Protein Ligases; Phosphorylation; Proteolysis; Real-Time Polymerase Chain Reaction; Receptor Cross-Talk; Receptor, Fibroblast Growth Factor, Type 1; Tandem Mass Spectrometry; Tyrosine; Ubiquitin-Protein Ligases; Ubiquitination
PubMed: 25292214
DOI: 10.1126/scisignal.2005290 -
Biochimica Et Biophysica Acta Jan 2015In bioenergetic reactions, electrons are transferred long distances via a hopping mechanism. In photosynthesis and DNA synthesis, the aromatic amino acid residue,... (Review)
Review
In bioenergetic reactions, electrons are transferred long distances via a hopping mechanism. In photosynthesis and DNA synthesis, the aromatic amino acid residue, tyrosine, functions as an intermediate that is transiently oxidized and reduced during long distance electron transfer. At physiological pH values, oxidation of tyrosine is associated with a deprotonation of the phenolic oxygen, giving rise to a proton coupled electron transfer (PCET) reaction. Tyrosine-based PCET reactions are important in photosystem II, which carries out the light-induced oxidation of water, and in ribonucleotide reductase, which reduces ribonucleotides to form deoxynucleotides. Photosystem II contains two redox-active tyrosines, YD (Y160 in the D2 polypeptide) and YZ (Y161 in the D1 polypeptide). YD forms a light-induced stable radical, while YZ functions as an essential charge relay, oxidizing the catalytic Mn₄CaO₅ cluster on each of four photo-oxidation reactions. In Escherichia coli class 1a RNR, the β2 subunit contains the radical initiator, Y122O•, which is reversibly reduced and oxidized in long range electron transfer with the α2 subunit. In the isolated E. coli β2 subunit, Y122O• is a stable radical, but Y122O• is activated for rapid PCET in an α2β2 substrate/effector complex. Recent results concerning the structure and function of YD, YZ, and Y122 are reviewed here. Comparison is made to recent results derived from bioengineered proteins and biomimetic compounds, in which tyrosine-based charge transfer mechanisms have been investigated. This article is part of a Special Issue entitled: Vibrational spectroscopies and bioenergetic systems.
Topics: Amino Acid Sequence; Biomimetics; DNA; Electron Transport; Electrons; Energy Metabolism; Models, Molecular; Molecular Sequence Data; Oxidation-Reduction; Photosystem II Protein Complex; Protein Engineering; Protons; Tyrosine
PubMed: 25260243
DOI: 10.1016/j.bbabio.2014.09.003 -
Life Sciences Sep 1984Tyrosine, the amino acid precursor of catecholamines, increases blood pressure (BP) in hemorrhaged hypotensive rats. Since tyrosine may also be decarboxylated to form...
Tyrosine, the amino acid precursor of catecholamines, increases blood pressure (BP) in hemorrhaged hypotensive rats. Since tyrosine may also be decarboxylated to form tyramine, which releases norepinephrine from sympathetic terminals, we tested the hypothesis that tyramine formation might mediate tyrosine's ability to increase BP. Three lines of evidence indicate that tyrosine does not act via this mechanism: pretreatment with reserpine blocked tyramine's but not tyrosine's pressor activity; pretreatment with hexamethonium left tyramine's effect intact but blocked the pressor response to tyrosine; and plasma tyramine did not increase after an hemodynamically-active dose of tyrosine (100 mg/kg).
Topics: Animals; Blood Pressure; Dose-Response Relationship, Drug; Hexamethonium Compounds; Hypotension; Male; Rats; Rats, Inbred Strains; Reserpine; Tyramine; Tyrosine
PubMed: 6472051
DOI: 10.1016/0024-3205(84)90192-9