Tyrosine plasma concentration

The liver is also the principal metabolic center for hydrophobic amino acids, and hence changes in plasma concentrations or metabolism of these molecules is a good measure of the functional capacity of the liver. Two of the commonly used aromatic amino acids are phenylalanine and tyrosine, which are primarily metabolized by cytosolic enzymes in the liver [1,114-117]. Hydroxylation of phenylalanine to tyrosine by phenylalanine hydroxylase is very efficient by the liver first pass effect. In normal functioning liver, conversion of tyrosine to 4-hy-droxyphenylpyruvate by tyrosine transaminase and subsequent biotransformation to homogentisic acidby 4-hydroxyphenylpyruvic acid dioxygenase liberates CO2 from the C-1 position of the parent amino acid (Fig. 5) [1,118]. Thus, the C-1 position of phenylalanine or tyrosine is typically labeled with and the expired C02 is proportional to the metabolic activity of liver cytosolic enzymes, which corresponds to functional hepatic reserve. Oral or intravenous administration of the amino acids is possible [115]. This method is amenable to the continuous hepatic function measurement approach by monitoring changes in the spectral properties of tyrosine pre- and post-administration of the marker. 

Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinases inhibitor approved for use in patients with chronic myelogenous leukemia after ima-tinib treatment and for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Maximum plasma concentrations (Cmax) of dasatinib are observed between 0.5 and 6 hours (Tmax) following oral administration. Dasatinib is extensively metabolized in humans, primarily by the cytochrome P450 enzyme 3A4. CYP3A4 was the primary enzyme responsible for the formation of the active metabolite. The overall mean terminal half-life of dasatinib is 3-5 hours. Adverse events included mild to moderate diarrhea, peripheral edema, and headache. Neutropenia and myelosuppression were common toxic effects. 

In a study of plasma concentrations of 33 amino acids, 159 subjects were recruited, of whom 107 were ecstasy users (93). The subjects were grouped according to cumulative lifetime use under 100 tablets (n = 34), 100-499 tablets (n = 42), 500-2500 tablets (n = 30), abstinent subjects (n = 11), and never users (n = 41). All were ecstasy free for at least 3 days, as verified by toxicological analysis. In 49% of the users, the time to the last use of ecstasy was 1 month or less. There were significant reductions in the serum concentrations of phosphoserine, glutamate, citrul-line, methionine, tyrosine, and histidine. Based on findings from other studies, the authors speculated that the reductions in serine and methionine may underlie psychosis associated with the use of ecstasy. Reduced glutamate may also add to the burden of psychiatric symptoms in ecstasy users. 

In 43 patients, raised plasma concentrations of FLT3-L (an fms-like tyrosine kinase) in patients who had previously received chemotherapy predicted the stage of recovery of the bone-marrow compartment (40). FLT3-L seems to identify the hkelihood that the patient will have severe thrombocytopenia if additional cytostatic therapy is given. Knowledge of bone-marrow activity... 

Figure 5.4. Schematic representation of the hybrid QSPR-PD model for corticosteroid action on tyrosine aminotransferase (TAT) induction in rat hepatocytes. In this model, the free intracellular concentration is a constant fraction (a) of the plasma concentration, Bmax is the total amount of glucocorticoid receptor (GR), and Kq is an equilibrium dissociation constant.17...

Because the hver metabohzes the aromatic amino acids (i.e., phenylalanine, tyrosine, and tryptophan), methionine, and glutamine, the plasma concentrations of these amino acids are elevated in cirrhotic patients. Plasma concentrations of the branched-chain amino acids (BCAAs) (i.e., valine, leucine, and isoleucine) often are depressed because these amino acids are metabohzed by skeletal muscle. This altered plasma aminogram contributes to the development of hepatic encephalopathy. 

The plasma concentration of LNAA competes with tryptophan for uptake into the brain. The extent of uptake and net utilization influences levels in blood. Like tryptophan, tyrosine and phenylalanine are mainly metabolized in the liver.199 However, the branched-chain amino acids (BCAA) are taken up and metabolized mainly by skeletal muscle and little by the liver.200 Thus, following a meal, the BCAA rise more in peripheral blood than the other LNAA and other indispensable amino acid levels that are influenced by liver metabolism. The BCAA, therefore, have the dominating effect of the LNAA as a group on brain tryptophan uptake. 

Isoprenaline — The administration of isoprenaline intraperito-neally to rats caused a significant decrease in plasma concentration of tryptophan as well as tyrosine.53 Since propranolol, the P-adrenergic antagonist,... 

Toluene — Toluene, after intraperitoneal injections or after inhalation, caused a decrease in rat plasma concentrations of tryptophan as well as of tyrosine.54 The mechanism for this is not clear. It may be related to the direct effect of toluene on the liver cell membranes, with a subsequent increase in liver cell uptake of amino acids. 

Eriksson, T. and Carlsson, A., Adrenergic influence on rat plasma concentrations of tyrosine and tryptophan, Life Sci., 30, 1465, 1982. 

Voog, L. and Eriksson T., Toluene-induced decrease in rat plasma concentrations of tyrosine and tryptophan, Acta Pharmacol. Toxicol., 54, 151, 1984. 

The neutral amino acids alanine, serine, threonine, asparagine, glutamine, valine, leucine, isoleucine, phenylalanine, tyrosine, tryptophan, histidine and citrulline share a common transporter at the luminal border of the epithelial cells in the renal tubuli and the epithelial cells in the small intestine [16]. In Hartnup disorder an impairment of this transporter leads to hyperexcretion of these neutral amino acids and to intestinal malabsorption. Excretion of tryptophan metabolites kynurenine and N-methyl-nico-tinamide is reduced. Plasma concentrations of the affected amino acids may be low normal or reduced. The inheritance is autosomal recessive. The hph2-deficient mouse has been postulated as a model for Hartnup disorder [17]. Affected persons may be asymptomatic, while some demonstrate pellagra-like photodermatitis or cerebellar ataxia due to a nicotinamide deficiency and respond well to the administration of nicotinamide [16]. 

In liver failure the plasma concentrations of the aromatic amino acids (AAAs) tyrosine, phenylalanine, and tryptophan increase, probably because they are predominantly broken down in the liver, whereas the plasma levels of BCAAs decrease while they are degraded in excess in muscle as a consequence of hepatic failure-induced catabolism. As AAAs and BCAAs are all neutral amino acids and share a common transporter across the blood-brain barrier (system L carrier), changes in their plasma ratio are reflected in the brain, subsequently disrupting the neurotransmitter profile of the catecholamines and indoleamines (see sections on tyrosine and tryptophan). It has been hypothesized that this disturbance contributes to the multifactorial pathogenesis of hepatic encephalopathy. In line with this hypothesis it has been suggested that normalization of the amino acid pattern by supplementing extra BCAAs counteracts hepatic encephalopathy. 

Lequea et al. used the activity of tyrosine apodecarboxylase to determine the concentration of the enzyme cofactor pyridoxal 5 -phosphate (vitamin B6). The inactive apoenzyme is converted to the active enzyme by pyridoxal 5 -phosphate. By keeping the cofactor the limiting reagent in the reaction by adding excess apoenzyme and substrate, the enzyme activity is a direct measure of cofactor concentration. The enzymatic reaction was followed by detecting tyramine formation by LCEC. The authors used this method to determine vitamin B6 concentrations in plasma samples. 

There is probably one more mechanism of MPO-mediated lipid peroxidation. Kettle and Candaeis [174] have studied the oxidation of tryptophan by neutrophil MPO. They suggested that tryptophan, which is present in plasma at the similar concentration as tyrosine and has a similar one-electron reduction potential, can contribute to oxidative stress at inflammation sites. It was proposed that the formed tryptophan free radicals may stimulate oxidative stress during inflammation. 

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