Disease relevance of tyrosine

• Patients with phenylketonuria (PKU) have a diet-controlled deficiency in the conversion of phenylalanine (Phe) to tyrosine (Tyr), leading to decreased production of noradrenaline, adrenaline, and dopamine [1].
• The effect of obesity and tyrosine (tyr) supplements on catecholamine metabolism in 12 normal weight and nine obese adult women was studied [2].
• To further elucidate the role of Stat3 in breast cancers, the expression patterns of Stat3 and Phospho-tyrosine residue 705 (Tyr705) Stat3 were correlated with survival outcome and clinicopathological parameters in a large cohort of node-negative breast cancer tumors [3].
• The Phe/Cre ratios for five urines from patients with PKU ranged from 0.162 to 0.521, and the Tyr/Cre ratio for tyrosinemia was 0.147 [4].
• The ratios of Tyr/Cre, Phe/Cre, and Trp/Cre for Lowe syndrome were 0.497, 0.321, and 0.495, respectively [4].

Psychiatry related information on tyrosine

• We conclude that the route of administration is an important variable influencing the effects of Phe on feeding behavior, and that these effects are not readily explained by plasma or brain Phe and Tyr concentrations [5].
• A few normal subjects had low TYR and TRP transport values, as observed in patients with affective disorders [6].
• Overall reaction times of a central task were fastest after the BAL[1:1] meal concomitant to the highest overall tyrosine (Tyr) to LNAA ratio [7].

High impact information on tyrosine

• Although cells transfected with c-fms genes containing either Tyr969 or Phe969 were not transformed, cotransfection of these genes with CSF-1 complementary DNA induced transformation, with c-fms(Phe969) showing significantly more activity than c-fms(Tyr969) [8].
• Forty C-terminal amino acids of the normal receptor are replaced by 11 unrelated residues in the feline v-fms oncogene product, deleting a C-terminal tyrosine residue (Tyr969) whose phosphorylation might negatively regulate the receptor kinase activity [8].
• Thr 14 and Tyr 15 are phosphorylated maximally during G2 phase but dephosphorylated abruptly at the G2/M transition, concomitant with activation of p34cdc2 kinase [9].
• For neurochemistry, basal and K(+)-evoked release of the endogenous amino acids GABA, glutamate (Glu), aspartate (Asp), and tyrosine (Tyr) from micropunches of the CIC were measured in 8 age-paired animals from the 2 age groups using high-performance liquid chromatography [10].
• In contrast, tissue content as well as basal and evoked release of Glu, Asp, Tyr, and 3H-ACh was similar between the 2 age groups [10].

Chemical compound and disease context of tyrosine

• Therapeutic addition of Tyr to diets of mothers with even mild hyperphenylalaninaemia should be approached with caution as mild co-elevation of Phe and Tyr in the fetus may be harmful [11].
• Three liver-specific growth media, respectively free of arginine (Arg-), tyrosine (Tyr-) and glucose (G-), have been used to characterize cells of the rat H4IIEC3, human HepG2 and mouse BW hepatoma lines [12].

Biological context of tyrosine

• These results strongly suggest that like the STATs, the IRFs are also modulated by Tyr phosphorylation that affects their biological activities [13].
• Substitution of Asn(726) with Phe or Tyr also produces self-poisoning enzymes, implicating stacking interactions in the increased kinetics of DNA cleavage by Top1N726Hp and Top1N726Fp [14].
• The data indicate that decreased IR tyr phosphorylation in hyperglycemia-induced insulin resistance is not due to enhanced dephosphorylation [15].
• Gyrase containing mutations in the A subunit at either the active-site tyrosine (Tyr122) or Ser83 (a residue known to be involved in quinolone interaction) failed to halt the progress of the polymerase [16].
• We conclude that urinary catecholamine metabolite production is related to body composition and to tyr intake in normal weight women [2].

Anatomical context of tyrosine

• To assess tyr dephosphorylation, IRs of insulin-stimulated permeabilized adipocytes were labeled with [gamma-32P]ATP and chased for 2 min with unlabeled ATP in the presence of EDTA [15].
• Studying normal human keratinocytes (NHKs), here we demonstrate strong expression of the Src family kinases Src, Yes, and Fyn; Src family kinase-dependent stimulation of Tyr 845 by EGF; and potent inhibition of NHK proliferation and migration by two Src family kinase inhibitors PP1 and PD173952 [17].
• Tyr/Phe restriction also inhibits Bcl-2 and Met restriction inhibits Bcl-XL in mitochondria [18].
• Treatment of serum-starved astrocytes with thrombin resulted in a rapid activation of tyrosine (Tyr) phosphorylation of a set of proteins including a prominent one with a molecular mass of 42 kDa (p42) [19].
• Restriction of Tyr/Phe or Met in DU145 and Met in PC3 reduces mitochondrial membrane potential (DeltaPsim) and induces caspase-dependent and -independent apoptosis [18].

Associations of tyrosine with other chemical compounds

• EMD 57033 caused concentration-dependent quenching of tyrosine (Tyr) fluorescence of hcTnC in the presence of Ca2+ (100 microM) and little change of the fluorescence in the presence of Mg2+ (2 mM) [20].
• Urinary excretion (24-hr) of beta-phenylethylamine (PEA), phenylacetic acid (PAA), phenylalanine (Phe), and p-tyrosine (Tyr), and plasma levels of PAA, Phe, and Tyr were examined in 18 normal children and 26 children diagnosed as having attention-deficit hyperactivity disorder (ADHD) [21].
• Plasma ghrelin levels were measured by RIA, plasma catecholamine concentrations were determined by HPLC with electrochemical detection, and Phe and Tyr levels were measured in an amino acid analyzer [1].
• No significant sex differences for CSF levels of HVA, 5-HIAA, Tyr, or Trp were found [22].
• CONCLUSIONS: A 62 g BCAA/TRP mixture decreases the availability of TYR and PHE for brain catecholamine synthesis and increases plasma prolactin consistent with lowered brain dopamine function [23].
• This supports the hypothesis that the mechanistic basis for the sigmoidal behavior is the same for both d-tyrosine activation by wild-type tyrosyl-tRNA synthetase and activation of l-tyrosine by the K233A variant [24].
• Bacillus stearothermophilus tyrosyl-tRNA synthetase binds d-tyrosine with an 8.5-fold lower affinity than that of l-tyrosine (K (D-Tyr)(d) = 102 microm) and exhibits a 3-fold decrease in the forward rate constant for the activation reaction (k (D-Tyr)(3) = 13 s(-1)) [25].

Gene context of tyrosine

• Although dual phosphorylation of Thr and Tyr residues confers full activation of ERK, in vitro studies suggest that a single phosphorylation on either Thr or Tyr may yield partial ERK activity [26].
• Mutation of the tyrosine residue (Tyr165) in this motif to phenylalanine resulted in increased surface expression of CTLA-4 [27].
• Additional mechanistic studies revealed that mGluR5 activation increased tyrosine (Tyr307) phosphorylation of PP2A, which was dependent on activation of a p60c-Src family tyrosine kinase, but not the epidermal growth factor receptor tyrosine kinase and resulted in dissociation of PP2A from mGluR5 and reduced PP2A activity [28].
• Cdk2-dn induction could inhibit Cdc25B activity and foster Cdk1 tyr phosphorylation within the S phase, temporally dissociating these events from Cdk1 activation at mitosis [29].
• Together, these observations demonstrate that one or more Src family kinases act upstream as well as downstream of ErbB1 to promote amphiregulin-dependent autocrine stimulation of NHKs and suggest that autocrine NHK proliferation is more dependent upon ERK activation than upon Tyr 845 phosphorylation [17].

Analytical, diagnostic and therapeutic context of tyrosine

• Kd for the drug-hcTnC interaction in the presence of Ca2+, determined by Tyr fluorescence titrations, was approximately 40 microM [20].
• After treatment with Tyr, ganglionic transmission was depressed significantly (p less than 0.05) in response to both low- and high-frequency stimulation (single: 0.44 +/- 0.04 mV; low: 0.22 +/- 0.12 mV; high: 0.26 +/- 0.07 mV) [30].
• PEG 8000 perturbs the structure of the protein surface, partially modifying the layer of water and the microenvironment of the superficial aromatic residues (tryptophan, TRP and TYR) which is in agreement with the modifications of the UV spectrum of albumin by PEG 8000 and circular dichroism (CD) spectrum at high temperatures [31].

References