Plasma Amino Acids in Relation to Cerebrospinal Fluid Monoamine Metabolites in Schizophrenic Patients and Healthy Controls

1985 ◽  
Vol 147 (3) ◽  
pp. 276-282 ◽  
Author(s):  
Lars Bjerkenstedt ◽  
Gunnar Edman ◽  
Lars Hagenfeldt ◽  
Göran Sedvall ◽  
Frits-Axel Wiesel

SummaryCompared to healthy controls, unmedicated schizophrenic patients had significantly higher plasma concentrations of taurine, methionine, valine, isoleucine, leucine, phenylalanine, and lysine. Except for taurine, these amino acids share the L-transport system for neutral amino acids. In the patients, homovanillic (HVA) acid levels in CSF were decreased and the plasma levels of the amino acids competing with tyrosine and tryptophan for transport into the brain, were all negatively correlated to the CSF concentrations of HVA and 5-HIAA. These findings could be explained by a change in the affinity of the L-system or by a decrease in its overall capacity in schizophrenia. Raised plasma levels of the competing amino acids may limit the brain uptake of tyrosine, leading to a diminished dopamine turnover, and resulting in a compensatory development of supersensitive dopamine receptors.

1997 ◽  
Vol 27 (2) ◽  
pp. 477-481 ◽  
Author(s):  
T. ERIKSSON ◽  
L. LIDBERG

Background. Aggression has been suggested to be related to abnormal brain 5-HT activity. This amine is synthesized in brain from tryptophan, which is transported through the blood–brain barrier in competition with other amino acids. The relationship between tryptophan and its endogenous amino acid competitors in plasma might thus influence the availability of tryptophan in the brain and consequently brain 5-HT activity.Methods. Plasma amino acids were determined in 89 offenders who had committed various violent and non-violent crimes and in 14 healthy controls.Results. Both tryptophan and its competitors were higher in offenders who had committed violent crimes compared both with non-violent offenders and with controls. No difference was, however, seen in the relationship between tryptophan and its competitors.Conclusions. The results support the contention that violent behaviour is related to biochemical deviations but could not explain a possible decreased brain 5-HT activity.


2014 ◽  
Vol 94 (2) ◽  
pp. 323-330 ◽  
Author(s):  
K. A. G. de Ridder ◽  
C. Farmer ◽  
C. F. M. de Lange ◽  
A. K. Shoveller ◽  
P. H. Luimes

de Ridder, K. A. G., Farmer, C., de Lange, C. F. M., Shoveller, A. K. and Luimes, P. H. 2014. Plasma amino acids, prolactin, insulin and glucose concentrations in lactating sows following venous infusion of isoleucine, leucine, lysine, threonine or valine. Can. J. Anim. Sci. 94: 323–330. The amino acid supply to lactating sows affects their milk yield, and the current study aims at establishing whether this is mediated via increases in concentrations of insulin and prolactin, two hormones that are important for lactation. Six multiparous Yorkshire sows (252.8±18.5 kg body weight) were fitted with an ear vein catheter and were used in a 6×6 Latin square design experiment from days 7 to 10 of lactation (am and pm infusions on 3 consecutive days). Sows were fed a commercial corn and soybean meal diet (17.1% crude protein) three times daily (1.5 kg at 0600 and 1200, 3.0 kg at 1830). Starting 2 h after the 0600 or 1200 feeding, sows received an infusion of saline (control), isoleucine, leucine, lysine, threonine or valine at a rate of 33 mL min−1during 30 min. The infused dose was equivalent to 18±0.9% of true ileal digestible intake for each of the amino acids. Serial blood samples were taken, starting 30 min prior to infusion and until 240 min after infusion. Plasma concentrations of amino acids, prolactin, insulin, and glucose were determined. Data were analyzed as repeated measurements and also using areas under the curve. Intravenous infusion with each of the five amino acids studied increased the corresponding free plasma amino acid concentrations (P<0.05). However, concentrations of prolactin, insulin, and glucose were not affected by infusion of any of the amino acids studied (P>0.10). Therefore, supplying intravenously 18% of the daily intake of isoleucine, leucine, lysine, threonine or valine brings about expected increases in amino acids, but does not alter the short-term response in prolactin, insulin or glucose concentrations of lactating sows.


1971 ◽  
Vol 41 (4) ◽  
pp. 301-307 ◽  
Author(s):  
I. L. Craft ◽  
T. J. Peters

1. Plasma amino acids have been determined in healthy untreated women and in those receiving synthetic steroids to suppress ovulation. Both groups were studied early in the cycle when endogenous sex hormone production is low, and again later in the same cycle, when endogenous or exogenous hormones are at high concentrations respectively. 2. In normal women there is a significant decrease in plasma concentrations of serine, glutamate and ornithine, and of total amino acids in the second half of the cycle. 3. At this time those taking oral contraceptives have significant decreases in plasma concentrations of proline, glycine, alanine, valine, leucine and tyrosine, and of total plasma amino acids. In addition plasma glutamate, glycine, isoleucine and tyrosine concentrations are significantly lower than in normal women. 4. In the interval between completing one course of contraceptive pills and commencing the next, total plasma amino acid concentration reverts to normal, but a significant decrease in plasma glycine concentration persists. 5. It is suggested that these changes are due to the influence of endogenous and exogenous sex hormones respectively.


2003 ◽  
Vol 77 (1) ◽  
pp. 3-10 ◽  
Author(s):  
L. A. Rubiot

AbstractThree experiments were carried out to determine plasma amino acids concentrations in circulating, portal and hepatic blood of growing male Wistar rats given diets containing lactalbumin, faba beans or chickpeas as the only protein source. Diets contained the same amount of digestible energy (15·5 kJ/g) and protein (lactalbumin in controls or legume proteins in the experimental diets; 100 g/kg). Appropriate amounts of essential synthetic amino acids were also added to legume-based diets taking into account their amino acid composition to equalize them to control (lactalbumin) diets. Portal blood flow (8·7±0·3 ml/min) was measured by using a transit-time ultrasound flow probe. Higher (P < 001) plasma concentrations of methionine than of controls were determined in hepatic veins of legume-fed rats. In contrast, lower (P < 001) concentrations of threonine, proline, valine, leucine, phenylalanine and lysine than those of controls were found in faba bean- and chickpea-fed rats. The same result as hepatic was obtained for portal and circulating plasma samples except that alanine and histidine values of legume-fed rats were also lower (P < 001) than controls. Calculated net afferent appearance rates of amino acids to the liver were lower (P < 001) than controls in rats given faba bean and chickpea diets for threonine, alanine, proline, valine, leucine, phenylalanine and lysine. This lower contribution of amino acids to the liver mainly via the portal vein in faba bean or chickpea-fed rats might explain previously reported differences in protein utilization and growth in comparison with animals given other protein sources (lactalbumin).


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Mayela Vaquero-Baez ◽  
Araceli Díaz-Ruíz ◽  
Luis Tristán-López ◽  
Carlos Aviña-Cervantes ◽  
Carlos Torner ◽  
...  

Abstract Purpose The aim of present study is to measure plasma clozapine (CLZ) and N-desmethyl clozapine (DMC) as biomarkers to correlate drug concentrations with the appearance of preclinical adverse hematic effects. Methods A high-performance liquid chromatographic method, using a diode-array (ultraviolet) detector, was validated to obtain reliable concentrations of CLZ and DMC, its main metabolite, in plasma of 41 schizophrenic patients taking CLZ. Blood neutrophils and leucocytes counting were concurrently assessed as a proxy to subclinical adverse reactions. Results The analytical method employed was linear, reproducible, and stable to measure concentrations of CLZ between 30 and 1000 ng/mL, while 12.5–560 ng/mL of the metabolite. The method allowed us to correlate CLZ plasma concentrations, the time taking CLZ and CLZ dose as determinants of neutrophils’ counting with a R2 = 0.447, using a multiple regression analysis model. Likewise, the correlation of leucocyte counting vs CLZ plasma levels and CLZ time, showed a R2 = 0.461. DMC correlated significantly with both neutrophils and leucocytes counting, but was excluded from the regression when CLZ concentration was included in the model. Finally, no other hematological adverse reactions were recorded. One patient presented a cardiovascular complication. The negative correlation between clozapine and neutrophil count observed in patients, suggest that CLZ itself, but not DMC, could be related to hematologic side-effects. Conclusion The findings of this study, demonstrate for the first time, that plasma levels of CLZ and time taking the drug are independent determinants of blood neutrophils and leucocytes, so the monitoring of plasma CLZ may be useful in the clinic practice to determine safe dosing of the drug.


2005 ◽  
Vol 94 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Gerdien C. Melis ◽  
Petra G. Boelens ◽  
Joost R. M. van der Sijp ◽  
Theodora Popovici ◽  
Jean-Pascal De Bandt ◽  
...  

Enhancement of depressed plasma concentrations of glutamine and arginine is associated with better clinical outcome. Supplementation of glutamine might be a way to provide the patient with glutamine, and also arginine, because glutamine provides the kidney with citrulline, from which the kidney produces arginine when plasma levels of arginine are low. The aim of the present study was to investigate the parenteral and enteral response of the administered dipeptide Ala-Gln, glutamine, citrulline and arginine. Therefore, seven patients received 20 g Ala-Gln, administered over 4 h, parenterally or enterally, on two separate occasions. Arterial blood samples were taken before and during the administration of Ala-Gln. ANOVA and a pairedttest were used to test differences (P<0·05). Ala-Gln was undetectable with enteral administration, whereas Ala-Gln remained stable at a plasma concentration of 268 μmol/l throughout parenteral infusion and rapidly decreased towards zero after infusion was stopped. The highest level of glutamine was observed with parenteral infusion of the dipeptide, although enteral infusion also significantly increased plasma levels of glutamine. The highest plasma response of citrulline was observed with the enteral administration of the dipeptide, although parenteral administration also increased plasma levels of citrulline. Plasma arginine increased significantly with parenteral infusion, but not with enteral administration of Ala-Gln. In conclusion, administrations of Ala-Gln, parenteral or enteral, resulted in an increased plasma glutamine response, as compared with baseline. Interestingly, in spite of the high availability of citrulline with enteral administration of the dipeptide, only parenteral infusion of Ala-Gln increased plasma arginine concentration.


1974 ◽  
Vol 46 (4) ◽  
pp. 559-562 ◽  
Author(s):  
B. H. Buxton ◽  
D. A. Stewart ◽  
I. M. Murray-Lyon ◽  
G. Curzon ◽  
R. Williams

1. Sixteen plasma amino acids were measured serially in an experimental model of acute hepatic failure produced in the pig by devascularization of the liver. 2. Significant increases in the concentration of glycine, alanine and methionine were observed. 3. Altered concentrations in plasma of neutral amino acids which compete with tryptophan for transport into the brain had no apparent influence on brain tryptophan concentration.


2007 ◽  
Vol 99 (4) ◽  
pp. 855-862 ◽  
Author(s):  
C. Moinard ◽  
I. Nicolis ◽  
N. Neveux ◽  
S. Darquy ◽  
S. Bénazeth ◽  
...  

Previous experimental studies have highlighted that citrulline (CIT) could be a promising pharmaconutrient. However, its pharmacokinetic characteristics and tolerance to loading have not been studied to date. The objective was to characterise the plasma kinetics of CIT in a multiple-dosing study design and to assess the effect of CIT intake on the concentrations of other plasma amino acids (AA). The effects of CIT loading on anabolic hormones were also determined. Eight fasting healthy males underwent four separate oral loading tests (2, 5, 10 or 15 g CIT) in random order. Blood was drawn ten times over an 8 h period for measurement of plasma AA, insulin and growth hormone (Gh). Urine samples were collected before CIT administration and over the next 24 h. None of the subjects experienced side effects whatever the CIT dose. Concerning AA, only CIT, ornithine (ORN) and arginine (ARG) plasma concentrations were affected (maximum concentration 146 (sem 8) to 303 (sem 11) μmol/l (ARG) and 81 (sem 4) to 179 (sem 10) μmol/l (ORN); time to reach maximum concentration 1·17 (sem 0·26) to 2·29 (sem 0·20) h (ARG) and 1·38 (sem 0·25) to 1·79 (sem 0·11) h (ORN) according to CIT dose). Even at high doses, urinary excretion of CIT remained low ( < 5 %). Plasma insulin and Gh were not affected by CIT administration. Short-term CIT administration is safe and well-tolerated. CIT is a potent precursor of ARG. However, at the highest doses, CIT accumulated in plasma while plasma ARG levels increased less than expected. This may be due to saturation of the renal conversion of CIT into ARG.


1992 ◽  
Vol 68 (2) ◽  
pp. 409-420 ◽  
Author(s):  
José L. Venero ◽  
Antonio J. Herrera ◽  
Alberto Machado ◽  
Josefina Cano

The contents of dopamine (DA) and serotonin (5-HT) and their metabolites were measured in rat substantia nigra and corpus striatum following dietary changes, including restriction of protein content (low-protein diet; LPD) and the contents of several large neutral amino acids (isoleucine, leucine, methionine, phenylalanine, tryptophan and valine) for 25 d. The LPD produced an increase in the concentration of tyrosine (TYR) in the two regions of the brain studied. This effect was also observed with all amino acid deficiencies studied except for valine in the substantia nigra, tryptophan in the striatum and phenylalanine in both regions. Likewise, the concentration of 5-hydroxyindolacetic acid (5-HIAA), the main metabolite of 5-HT, increased in the substantia nigra but not in the striatum after LPD, as well as with all the amino acid deficiencies studied, with the exception of tryptophan deficiency. In this case there was a dramatic effect on all components of the serotoninergic system, with decreases in the concentration of tryptophan (TRP; precursor), 5-HT and 5-HIAA. This behaviour clearly shows an interrelationship between precursor (TRP) availability and 5-HT synthesis and metabolism. With valine deficiency, dopaminergic and serotoninergic systems demonstrated opposite effects in the substantia nigra and the corpus striatum, and the behaviour of the two monoamines was also opposite within each structure. The significance of these changes is discussed.


2021 ◽  
Vol 12 ◽  
Author(s):  
Abdelrahim Alqudah ◽  
Mohammed Wedyan ◽  
Esam Qnais ◽  
Hassan Jawarneh ◽  
Lana McClements

The perturbation in plasma free amino acid metabolome has been observed previously in diabetes mellitus, and is associated with insulin resistance as well as the onset of cardiovascular disease in this population. In this study, we investigated, for the first time, changes in the amino acid profile in a group of people with and without type 2 diabetes (T2D) with normal BMI, from Jordan, who were only managed on metformin. Twenty one amino acids were evaluated in plasma samples from 124 people with T2D and 67 healthy controls, matched for age, gender and BMI, using amino acids analyser. Total amino acids, essential amino acids, non-essential amino acids and semi-essential amino acids were similar in T2D compared to healthy controls. Plasma concentrations of four essential amino acids were increased in the presence of T2D (Leucine, p &lt; 0.01, Lysine, p &lt; 0.001, Phenylalanine, p &lt; 0.01, Tryptophan, p &lt; 0.05). On the other hand, in relation to non-essential amino acids, Alanine and Serine were reduced in T2D (p &lt; 0.01, p &lt; 0.001, respectively), whereas Aspartate and Glutamate were increased in T2D compared to healthy controls (p &lt; 0.001, p &lt; 0.01, respectively). A semi-essential amino acid, Cystine, was also increased in T2D compared to healthy controls (p &lt; 0.01). Citrulline, a metabolic indicator amino acid, demonstrated lower plasma concentration in T2D compared to healthy controls (p &lt; 0.01). These amino acids were also correlated with fasting blood glucose and HbA1c (p &lt; 0.05). Glutamate, glycine and arginine were correlated with the duration of metformin treatment (p &lt; 0.05). No amino acid was correlated with lipid profiles. Disturbances in the metabolism of these amino acids are closely implicated in the pathogenesis of T2D and associated cardiovascular disease. Therefore, these perturbed amino acids could be explored as therapeutic targets to improve T2D management and prevent associated cardiovascular complications.


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