Plasma Tyrosine Concentrations Research Articles

Altered tissue amino acid metabolism in acute T-2 toxicosis.

T-2 toxin is a Fusarium trichothecene mycotoxin that has been shown to alter brain neurochemistry and eating behavior in animals eating contaminated diets. Experiments were conducted to determine the role of altered tissue amino acid metabolism in the etiology of acute T-2 toxicosis. Fasted weanling rats were orally dosed with 0 or 2.0 mg T-2 toxin/kg body weight. Blood, brain, liver, and muscle tissue were excised 4 and 8 hr after dosing, and amino acid concentrations were determined. Hepatic enlargement coupled with reduced liver concentrations of free small neutral, large neutral, and basic amino acids were seen 4 hr after dosing. Brain and muscle amino acid concentrations were largely refractory to treatment, while the plasma concentrations of tyrosine and lysine, and the sum of the basic amino acids fell. Hepatic amino acid concentrations returned to control levels 8 hr after dosing at which time aminoacidemia was seen. This was due partially to an increase in plasma concentrations of large neutral amino acids including particularly the branched-chain amino acids. A subsequent experiment was conducted to determine the effect of T-2 toxin on 14C-leucine uptake and incorporation into protein in liver slices 4 hr after dosing. Exposure to T-2 toxin reduced total (free + protein-bound) uptake of leucine due primarily to reduced incorporation of leucine into newly-synthesized hepatic protein. It was concluded that reduced amino acid uptake by liver preceded aminoacidemia in acute T-2 toxicosis, although it is not clear how this might influence subsequent changes in brain neurochemistry and behavior.

Visual evoked potentials in phenylketonuria: association with brain MRI, dietary state, and IQ.

At separate institutions, pattern reversal visual evoked potentials (VEPs) were recorded in children and older patients with phenylketonuria and compared with MRI of the brain. In nine patients aged less than 14 years, who were still on a diet low in phenylalanine, VEPs were clearly abnormal in only one and the abnormalities seen on MRI were mild. In 27 patients aged 14-31 years VEPs were abnormal in more than 80%, with significant reduction of amplitude and prolongation of latency despite the general absence of visual symptoms and abnormalities on routine neuro-ophthalmological examination. Among the older patients there was no significant correlation between VEP measures and plasma phenylalanine or tyrosine concentrations; neither was the incidence of VEP abnormalities dependent on whether or not the patients were still on a low phenylalanine diet. Some VEP amplitude measures were inversely correlated with the MRI lesion score, perhaps reflecting the severity of white matter abnormalities in the parieto-occipital region. In the older patients the amplitude of VEPs to stimulation of the central 8 degrees of the visual field was significantly correlated with IQ. The study confirms the high incidence of subclinical visual pathway involvement in older children and adults with phenylketonuria, and suggests the possibility of a link between the abnormal appearance of subcortical white matter on MRI and a physiological index of function of the CNS. As there was no evidence of general intellectual decline, it is suggested that the correlation between central field VEP amplitude and IQ may reflect abnormal development during infancy. Abnormalities on MRI, on the other hand, seem to be more closely related to current dietary state and phenylalanine concentration.

Utilization of tyrosine-containing dipeptides and N-acetyl-tyrosine in hepatic failure

The impact of hepatic dysfunction on the elimination and hydrolysis of three potential tyrosine sources for total parenteral nutrition, the dipeptides L-alanyl-L-tyrosine (Ala-Tyr) and glycyl-L-tyrosine (Gly-Tyr), and N-acetyl-L-tyrosine (Nac-Tyr) were evaluated in six patients with hepatic failure (five chronic, one acute) and seven healthy subjects. In controls, whole-body clearance (Cltot) of Ala-Tyr was higher than of Gly-Tyr (3,169 +/- 214 vs. 1,780 +/- 199 mL/kg/min, P < .01), and both exceeded clearance of Nac-Tyr (309 +/- 29 mL/kg/min, P > .01). Both dipeptides were hydrolyzed and released tyrosine immediately. In hepatic failure, elimination and hydrolysis of Ala-Tyr and Gly-Tyr were comparable to controls, but Cltot of Nac-Tyr was reduced (236 +/- 26 mL/kg/min). Neither in controls nor in patients an increase in plasma tyrosine concentration was seen after Nac-Tyr, and the major part of Nac-Tyr infused was lost in urine. The Cltot of tyrosine as evaluated after Ala-Tyr infusion (with the immediate release of tyrosine) was severely reduced in hepatic failure (152.7 +/- 38.4 vs. 484.4 +/- 41.4 mL/kg/min, P < .001) and half-life (kle) was retarded from 14.4 +/- 1.4 to 90.2 +/- 32.2 minutes (P < .03). The authors conclude that acute and chronic hepatic dysfunction does not affect elimination and hydrolysis of the dipeptides Ala-Tyr and Gly-Tyr and the constituent amino acids are released immediately. Nac-Tyr elimination was not grossly affected by hepatic failure, but neither in healthy subjects nor in hepatic failure patients was an increase of tyrosine seen. Both dipeptides but not Nac-Tyr may serve as a tyrosine source in parenteral nutrition. Moreover, by its rapid hydrolysis, the use of Ala-Tyr, for the first time, enables a simple rapid nonisotope evaluation of tyrosine kinetics for assessment of liver function.

Utilization of tyrosine-containing dipeptides and N-acetyl-tyrosine in hepatic failure

The impact of hepatic dysfunction on the elimination and hydrolysis of three potential tyrosine sources for total parenteral nutrition, the dipeptides L-alanyl-L-tyrosine (Ala-Tyr) and glycyl-L-tyrosine (Gly-Tyr), and Nacetyl-L-tyrosine (Nac-Tyr) were evaluated in six patients with hepatic failure (five chronic, one acute) and seven healthy subjects. In controls, whole-body clearance (Cl tot) of Ala-Tyr was higher than of Gly-Tyr (3,169 ± 214 vs. 1,780 ± 199 mL/kg/min, P < .01), and both exceeded clearance of Nac-Tyr (309 ± 29 mL/kg/min, P > .01). Both dipeptides were hydrolyzed and released tyrosine immediately. In hepatic failure, elimination and hydrolysis of Ala-Tyr and Gly-Tyr were comparable to controls, but Cl tot of Nac-Tyr was reduced (236 ± 26 mL/kg/min). Neither in controls nor in patients an increase in plasma tyrosine concentration was seen after Nac-Tyr, and the major part of Nac-Tyr infused was lost in urine. The Cl tot of tyrosine as evaluated after Ala-Tyr infusion (with the immediate release of tyrosine) was severely reduced in hepatic failure (152.7 ± 38.4 vs. 484.4 ± 41.4 mL/kg/min, P < .001) and half-life (k le) was retarded from 14.4 ± 1.4 to 90.2 ± 32.2 minutes ( P < .03). The authors conclude that acute and chronic hepatic dysfunction does not affect elimination and hydrolysis of the dipeptides Ala-Tyr and Gly-Tyr and the constituent amino acids are released immediately. Nac-Tyr elimination was not grossly affected by hepatic failure, but neither in healthy subjects nor in hepatic failure patients was an increase of tyrosine seen. Both dipeptides but not NacTyr may serve as a tyrosine source in parenteral nutrition. Moreover, by its rapid hydrolysis, the use of AlaTyr, for the first time, enables a simple rapid nonisotope evalution of tyrosine kinetics for assessement of liver function.

Painful keratoderma and photophobia: Hallmarks of tyrosinemia type II

Tyrosinemia type II (Richner-Hanhart syndrome), which is caused by a deficiency of hepatic tyrosine aminotransferase, results in elevated plasma and urinary tyrosine concentrations. We describe a young boy who was seen at 6 months of age with red eyes, photophobia, and eye pain that were not suspected to be caused by tyrosinemia II until painful plantar keratoderma developed at 2½ years of age. Treatment with a diet low in tyrosine and phenylalanine reversed the manifestations of the disease. (J P EDIATR 1995;126:266-9)

Plasma amino acid and protein concentrations in infants fed human milk or a whey protein hydrolysate formula during the first month of life

The aim of the study was to compare growth parameters, biochemical indices of protein metabolism and plasma amino acid concentrations in infants fed either human milk (n = 12) or a whey protein hydrolysate formula (n = 13) during the first month of life. Growth and gain in skin fold thickness were similar in both groups whereas serum protein concentration was significantly decreased (57.4 +/- 3.9 versus 61.2 +/- 2.9 g/l) in the infants fed the whey hydrolysate formula. The discrepancies between the plasma amino acid pattern of the whey hydrolysate formula group and that of the human milk group lessened during the first month. Nevertheless, at a mean age of 33 days the plasma threonine concentration remained twice as high and the plasma tyrosine, phenylalanine and proline concentrations were significantly lower in the whey hydrolysate formula group than in the human milk group. Thus, compared with breast-fed infants, growth and most of the biological indices of protein metabolism were satisfactory in infants fed during the first month of life on a whey protein hydrolysate formula. Nevertheless, the decrease in total plasma protein concentration needs to be confirmed in a larger cohort of infants. In addition, further research is necessary to investigate the possible ways of reducing the hyperthreoninemia and preventing other plasma amino acid disturbances since it would be desirable to obtain plasma amino acid levels similar to those of breast-fed infants.

Plasma Phenylalanine and Tyrosine Responses to Different Nutritional Conditions (Fasting/Postprandial) in Patients With Phenylketonuria: Effect of Sample Timing

To evaluate the adequacy of dietary treatment in patients with phenylketonuria, the monitoring of plasma phenylalanine and tyrosine concentrations is of great importance. The preferable time of blood sampling in relation to the nutritional condition during the day, however, is not known. It was the aim of this study to define guidelines for the timing of blood sampling with a minimal burden for the patient. Plasma concentrations of phenylalanine and tyrosine were measured in nine patients with phenylketonuria who had no clinical evidence of tyrosine deficiency. These values were measured during the day both after a prolonged overnight fast, and before and after breakfast. Phenylalanine showed a small rise during prolonged fasting, while tyrosine decreased slightly. After an individually tailored breakfast, phenylalanine remained stable, while tyrosine showed large fluctuations. It is concluded that the patient's nutritional condition (fasting/postprandial) is not important in the evaluation of the phenylalanine intake. To detect a possible tyrosine deficiency, however, a single blood sample is not sufficient and a combination of a preprandial and postprandial blood sample on the same day is advocated.

Growth, nutrient intake and plasma phenylalanine and tyrosine concentrations of infants treated with phenex TM-1 amino acid modified medical food with iron

The objective of this study was to evaluate the effects of a new medical food (Phenex-1) on growth, nutrient intake and plasma phenylalanine (PHE) and tyrosine (TYR) concentrations of infants and toddlers with phenylketonuria (PKU). Ten full-term infants (5F, 5M) with classical PKU were placed on Phenex-1 as their primary protein source at a mean age of 11.8 days (range 7–20 days). Two infants received human milk and eight received proprietary infant formula as the source of PHE. Anthropometric measures were obtained by standard techniques, nutrient intakes were calculated using Amino Acid Analyzer© software, and plasma amino acids were analyzed by ion exchange chromatography. When compared to NCHS growth curves, mean head circumference and weight of subjects at birth were at the 75th percentile and greater than the 75th percentile at six months of age. Mean length was at the 75th percentile at birth and at six months of age. During the first three months of study mean PHE intake was 47 mg/kg (range 34–67 mg/kg) and mean TYR intake was 154 mg/kg (range 119–291 mg/kg). During the second three months of study mean PHE intake was 36 mg/kg (range 27–61 mg/kg) and mean TYR intake was 214 mg/kg (range 181–257 mg/kg). Mean protein intake during the study was consistently above RDAs; mean energy intake, except at month one, was below RDAs and the lowest mean value was 87% of RDA at 3 months of age. Mean plasma PHE (35 samples) during the course of the study was 258 μmol/L (range 6–1054 μmol/L) (NL 19–76 μmol/L). Twenty-three percent of samples were in the normal range; forty percent were < 121 μmol/L, 66% were < 303 μmol/L and 89% of samples were < 619 μmol/L. Mean plasma TYR was 47 μmol/L (range 16–98 μmol/L) (NL 25–148 μmol/L). Ninety-one percent of the 35 plasma TYR concentrations were in the normal range. Despite energy intakes that were below RDAs and plasma PHE that was < 121 μmol/L in 40% of the samples, Phenex-1 supported excellent growth and normal plasma TYR concentrations.

Decreased plasma proteins, increased total plasma-free amino acids, and disturbed amino acid metabolism in the hereditary severe anemia of the Belgrade laboratory (b/b) rat.

The plasma amino acid pattern has been investigated in severely anemic Belgrade laboratory (b/b) rats. Nonanemic heterozygous (b/+) or normal homozygous (+/+) rats of the same age (six weeks) were used as controls. Decreased plasma proteins, increased total free amino acid, and urea concentrations in plasma associated with increased urea and 3-methylhistidine urinary excretion were found, indicating protein and amino acid metabolic alterations in anemic b/b rats. Plasma alanine, glutamine, tyrosine, and phenylalanine concentrations were increased. The significantly reduced molar ratio between valine+leucine+isoleucine and phenylalanine+tyrosine suggested severe disturbance in the hepatic energy-producing system and derangement of hepatic energy status. Partial or complete reversal of the anemia within 3 days by red blood cell transfusion or within 3 weeks by iron treatment resulted in normalization of tyrosine, alanine, glutamine, and total amino acid concentrations in plasma, as well as of molar ratio between valine+leucine+isoleucine and phenylalanine+tyrosine. This indicated a better oxygen supply to the liver and normalization of the hepatic energy status. These findings suggest that the metabolic disturbances in the b/b rat are the consequence of hypoxia due to the severe anemia.

Does tyrosine act as a nutritional signal mediating the effects of increased feed intake on luteinizing hormone patterns in growth- restricted lambs?

We tested the hypothesis that the increase in LH secretion associated with elevated feed intake in nutritionally growth-restricted lambs is due to increased availability of tyrosine (TYR). Ovariectomized ewe lambs with abomasal cannulae were fed a complete diet in amounts (0.6 Mcal of net energy/day) sufficient to maintain a body weight of 21.7 +/- 1.0 kg between 10 and 32 wk of age. At 32 wk of age, lambs were assigned at random to one of three treatments: 1) maintenance feeding + abomasal infusion of water (M; n = 6); 2) maintenance feeding + abomasal infusion of TYR (M + TYR; n = 7); or 3) twice maintenance feeding + abomasal infusion of water (TM; n = 6). TYR (1.25 g/100 ml water) or water (100 ml) was delivered as a bolus injection at 0600, 1200, 1800, and 2400 h daily for 23 days. Plasma concentrations of TYR 10 and 22 days after initiation of treatments were higher (p less than 0.001) in the TM and M + TYR groups compared to the M group and were elevated (p less than 0.001) in the M + TYR group compared to the TM group. Concentrations of TYR in hypothalami were higher (p less than 0.01) in the M + TYR and TM groups than in the M group, and greater (p less than 0.005) in the M + TYR group compared to the TM group. Overall, there was a linear (p less than 0.001) correlation between plasma and hypothalamic concentrations of TYR.(ABSTRACT TRUNCATED AT 250 WORDS)

Route of Administration of Tryptophan and Tyrosine Affects Short-Term Food Intake and Plasma and Brain Amino Acid Concentrations in Rats ,

The effects of route of administration of tryptophan and tyrosine on food intake and diet selection and on plasma and brain tryptophan or tyrosine concentrations were studied. Tryptophan and tyrosine given intraperitoneally at 100 mg/kg body wt suppressed food intake by 33–45% over a 2-h feeding period beginning 30 min after injections. No preferential effect was shown for either the high carbohydrate or high protein diet choice. When given intragastrically at this dose, neither tryptophan nor tyrosine affected food intake. Tryptophan, but not tyrosine, at 200, 400 and 600 mg/kg body wt given intragastrically reduced food intake and carbohydrate diet intake by an average of 20 and 25%, respectively, in the first 2 h of feeding. Plasma and brain tryptophan were higher for 30 min following intraperitoneal tryptophan injections than after tryptophan given intragastrically at 100 mg/kg body wt. However, intraperitoneal tyrosine (100 mg/kg body wt) resulted in higher plasma tyrosine levels at 5–10 min but lower levels at 30 min than when tyrosine was given intragastrically. Brain tyrosine was higher after intraperitoneal treatment only at 10 min and was similar to intragastric treatment at other times. When these amino acids were given intragastrically at 400 mg/kg body wt, higher plasma tryptophan, plasma tyrosine and brain tyrosine were found than following intraperitoneal injection of the behaviorally effective dose (100 mg/kg body wt) at 30 min. Thus the reduced effect on food intake of tryptophan or tyrosine given intragastrically compared with intraperitoneally is not readily explained by their lower concentrations in plasma and brain preceding and at the time that the rats had access to food.

Effect of glucose and branched chain amino acid (BCAA) infusion on onset of liver regeneration and plasma amino acid pattern in partially hepatectomized rats

Immediately after 70% hepatectomy, rats were infused via the jugular vein with one of the following solutions: saline, 3% or 8% glucose solution, 3% BCAA solution, 8% Nutramin (17% BCAA) or 8% Nutramin enriched with BCAA (47% BCAA). Rats were killed 18, 21, 24 and 30 h after partial hepatectomy. The course of liver regeneration was assessed from incorporation of labeled thymidine into DNA and from hepatocyte mitotic activity. After partial hepatectomy a decrease of glycemia and increase of plasma phenylalanine concentrations were observed. Glucose infusion had a pronounced inhibiting effect on the onset of liver regeneration. The decreased incorporation of labeled thymidine into DNA and the decreased hepatocyte mitotic activity in glucose-infused rats were associated with higher plasma concentrations of tyrosine and phenylalanine. Parenteral administration of 3% BCAA solution and 8% Nutramin enriched with BCAA had a favourable effect on the onset of liver regeneration after partial hepatectomy compared with glucose- and Nutramin-infused groups. In BCAA-infused rats elevated levels of BCAA and decreased concentrations of tyrosine and phenylalanine were noted.

Pathophysiologische Regelmechanismen bei chronisch Schizophrenen

Two collectives of chronic schizophrenics were psychometrically rated by means of the BPRS and of Gebhardt's primary AMP-scales. Their scores of coexistent Positive and Negative Symptomatology were correlated with equivalents of catecholergic levels of tone as represented by plasma tyrosine concentration in its role as the catecholergic precursor. Levels of catecholergic tone state- and time-dependently correlated directly with Positive and inversely with Negative Symptomatology. Opposite ends of catecholergic tone from supra- to subnormal ranges ran parallel to a psychometric continuum from predominant Positive to predominant Negative Symptomatology, to a diagnostic continuum from "paranoid" to "disorganised/hebephrenic", and to a global metabolic continuum from under- to overweight. Findings did not support the hypothesis on psychotogenic dopaminergic supersensitivity. Postulated was a primary psychotogenic process of denervation or/and degeneration of a specific 'trigger system', and supersensitivity-induced neuronal damage was conjectured the biological substrate of Negative Symptomatology. A pathophysiological hypothesis put forth, corresponded with Cannon's Rules within the frame of functional neuronal plasticity.

Comparative Effects of Thermal and Surgical Trauma on Rat Muscle Protein Metabolism

A modified intraperitoneal pool flooding technique, employing L-3H-tyrosine, was developed for measuring muscle protein synthetic rates following traumatic injury. Sufficient radiolabeled tyrosine was injected intraperitoneally to effect a six-fold increase in plasma tyrosine concentration (124-800 microM) resulting in constant, sustained specific radioactivities in plasma- and intracellular-free tyrosine pools. Localized vs systemic effects of thermal and surgical trauma on gastrocnemius muscle protein turnover were assessed 2 and 4 days postinjury. Thermal trauma increased total, myofibrillar, and sarcoplasmic muscle protein synthesis (44%) and protein degradation (300%). Conversely, surgical trauma decreased synthesis of total (24%), myofibrillar (14%), and sarcoplasmic (43%) muscle proteins without altering protein degradation. Short-term restriction of pair-fed controls did not affect either aspect of protein turnover.

91 REDUCED SIZE ORTHOTOPIC LIVER TRANSPLANTATION (OLT) IN SMALL CHILDREN WITH HEREDITARY TYROSINEMIA (HT)

Prior to 1987 all pts with HT in Finland died in early years. In 1987 OLT on children was introduced in our country and since then 5 pts wirh HT have been diagnosed by high plasma tyrosine and urinary succinyl acetone (SAA) concentrations and enzyme analysis. In one pt, HT manifested acutely with bleeding, ascites and edema at 6 wks. Four presented with liver insufficiency and tubulopathy at 3 to 7 mos. Serurm α-fetoprotein (AFP) was 130-11000 times age matched median and liver CT showed tumor like nodules in most pts. The pts were treated by low tyrosine + low phenylalanine diet. In the pt with acute HT, blood exchanges and i.v. glutathione were used. One pt had several porphyria episodes which responded well to i.v. hemiarginate.

Influence of glucocorticoids on skeletal muscle proteolysis in normal and diabetic-adrenalectomized eviscerated rats

The effect on skeletal muscle proteolysis of acute (20-hour) glucocorticoid treatment (dexamethasone 1.5 mg/kg, subcutaneously [SC]) was tested using the eviscerated rat preparation. According to this method, the peripheral tissues (primerily the skeletal muscles) are isolated by functional hepatectomy-nephrectomy. Total proteolysis is estimated from the rate of rise of plasma tyrosine concentration in the presence of cycloheximide to block protein synthesis. Myofibrillar proteolysis is measured from the rate of release into the plasma of the nonreutilized, nonmetabolized amino acid 3-methylhistidine (3MH), in the absence of cycloheximide. In normal rats, dexamethasone increased total proteolysis by 20% and myofibrillar proteolysis by 75% (both P < .025 v saline controls). In diabetic-adrenalectomized rats prepared 2 weeks earlier (65 mg/kg streptozocin [STZ] followed by adrenalectomy), dexamethasone caused much greater increments in rates of total proteolysis (94%) and myofibrillar proteolysis (240%) (both P < .001 v saline controls). Because diabetic animals are extremely sensitive to glucocorticoid-induced proteolysis, we also examined whether the acute proteolytic effect of diabetes itself might be mediated by adrenal cortical hormones. Previously adrenalectomized rats studied 20 hours after STZ showed a 40% augmentation of total proteolysis ( P < .01), an effect similar to that produced by acute diabetes in rats with intact adrenals. We conclude that glucocortical hormones cause a catabolic effect on total and myofibrillar skeletal muscle protein which is exaggerated when the counteracting action of insulin is reduced, but that the excess proteolysis of acute insulin deficiency is independent of the endogenous glucocorticoids secretion.

Plasma tryptophan and tyrosine concentrations: determination using high performance liquid chromatography and fluorometric detection

Determination par HPLC et fluorimetrie des concentrations de tryptophane et tyrosine plasmatiques (composes naturellement fluorescents). Un aliquote de plasma deproteineise par de l'acide perchlorique est immediatement injecte dans une colonne HPLC et la fluorescence est quantifiee

Skeletal muscle proteolysis in rats with acute streptozocin-induced diabetes.

Skeletal muscle proteolysis was studied in rats 1 day after induction of diabetes with 65 mg/kg streptozocin. An evisceration procedure, including functional hepatectomy-nephrectomy, was performed, and the rate of proteolysis in the remaining tissues, primarily skeletal muscles, was evaluated over 2 h. With cycloheximide to block protein synthesis, total protein breakdown was measured from the rate of rise in plasma tyrosine concentration. The rate of degradation of contractile (myofibrillar) protein was estimated from the rate of rise in plasma concentration of 3-methylhistidine released from the breakdown of actomyosin. Compared with nondiabetic control preparations, the total protein degradation rate was increased 30% by diabetes (P less than .001), and myofibrillar catabolism was accelerated by 60% (P less than .005). In diabetes, the increase in proteolysis was accompanied by reductions in circulating insulin to 25-50% of normal level, whereas food intake did not differ from control. Treatment of diabetic rats with exogenous insulin, including acute infusions postoperatively, completely reversed the proteolytic effects of diabetes. The findings demonstrate that the hypoinsulinemia of acute diabetes increases the catabolism of skeletal muscle protein and that the inhibitory effect of normal levels of insulin includes a specific action to restrain myofibrillar proteolysis.

Raised plasma concentrations of 3-methoxy-4-hydroxyphenylethyleneglycol in cirrhotic patients with or without hepatic encephalopathy.

We measured the plasma concentration of a centrally derived noradrenaline (NA) metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), in 20 cirrhotic patients (eight with (group A) and 12 without (group B) hepatic encephalopathy (HE] and in 14 age matched healthy subjects to study if the central NA metabolism would be altered in liver cirrhosis patients, particularly in those with HE. The mean (SEM) plasma MHPG concentrations in the patient groups, group A (74.9 (8.6) pmol/l) and B (54.8 (7.2) pmol/l), were significantly (p less than 0.01) greater than in the control group (22.3 (2.0) pmol/l), and that in group A was significantly (p less than 0.05) greater than in group B. The plasma concentration of MHPG observed in these study subjects (n = 34) correlated (rs = 0.77, p less than 0.01) more strongly with the ratio of plasma catecholamine precursor amino acids (tyrosine and phenylalanine) to other neutral amino acids (tryptophan, leucine, isoleucine, and valine) known to compete with catecholamine precursor amino acids for uptake into the brain than with plasma concentration of tyrosine plus phenylalanine alone (rs = 0.63, p less than 0.01). In addition, the mean plasma MHPG concentrations measured in another group of eight cirrhotic patients (group C) during HE (79.3 (10.6) pmol/l) was significantly (p less than 0.01) greater than that measured after the recovery from HE (47.2 (5.2) pmol/l). The results suggest that the central NA metabolism may be altered in patients with liver cirrhosis, particularly in those with HE, and that the derangement in the central NA metabolism may be associated not only with an increase in plasma catecholamine precursor amino acids but also with a decrease in branched chain amino acids.

Decreases in tyrosine and p-hydroxyphenylglycol caused by various antidepressants

The effects of eleven different antidepressant drugs on brain p-hydroxyphenylglycol (pHPG) and on brain and plasma tyrosine concentrations were investigated in rats. Imipramine, amitriptyline, amoxapine, desmethylimipramine and iprindole (20 mg/kg each) and bupropion (50 mg/kg) decreased brain pHPG levels 4.5 or 6 hr after injection. Each of these drugs also significantly reduced plasma tyrosine levels 1.5 hr after injection. In contrast, zimelidine, amitriptylinoxide, trimipramine and trazodone had no significant effect on either brain pHPG or plasma tyrosine. Mianserin significantly lowered plasma tyrosine but produced a nonsignificant decrease in brain pHPG. The decreases in brain pHPG caused by the various drugs were significantly correlated with 3,4-dihydroxyphenylethyleneglycol. Moreover, decreases in brain pHPG and brain and plasma tyrosine concentrations were correlated with the potencies of these drugs to inhibit in vitro norepinephrine uptake. These results suggest the possibility that noradrenergic (or similar) mechanisms regulate both pHPG and tyrosine levels. However, the decreases in pHPG cannot be explained entirely by a deficiency in tyrosine, since the depletions in pHPG were much larger and longer lasting than those of tyrosine.