Plasma Amino Acid Profiles Research Articles

Regulation of the plasma amino acid profile by leucine via the system L amino acid transporter.

Plasma concentrations of amino acids reflect the intracellular amino acid pool in mammals. However, the regulatory mechanism requires clarification. In this study, we examined the effect of leucine administration on plasma amino acid profiles in mice with and without the treatment of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) or rapamycin as an inhibitor of system L or mammalian target of rapamycin complex 1, respectively. The elevation of plasma leucine concentration after leucine administration was associated with a significant decrease in the plasma concentrations of isoleucine, valine, methionine, phenylalanine, and tyrosine; BCH treatment almost completely blocked the leucine-induced decrease in plasma amino acid concentrations. Rapamycin treatment had much less effects on the actions of leucine than BCH treatment. These results suggest that leucine regulates the plasma concentrations of branched-chain amino acids, methionine, phenylalanine, and tyrosine, and that system L amino acid transporters are involved in the leucine action.

Maternal Low Quality Protein Diet Alters Plasma Amino Acid Concentrations of Weaning Rats.

Several studies have indicated the influence of a maternal low protein diet on the fetus. However, the effect of a maternal low quality protein diet on fetal growth and development is largely unknown. Wistar rats (11 weeks old) were mated and maintained on either a chow diet with 20% casein (n = 6) as the control group (C), or a low quality protein diet with 20% wheat gluten (n = 7) as the experimental group (WG) through gestation and lactation. Maternal body weights were similar in both groups throughout the study. Birth weights were not influenced by maternal diet and offspring body weights during lactation were similar between the groups. Offspring’s plasma amino acid profiles showed that plasma methionine, glutamine and lysine were significantly lower and aspartic acid, ornithine and glycine-proline were significantly higher in the WG. Plant based protein comprises an important part of protein intake in developing countries. It is well-known that these diets can be inadequate in terms of essential amino acids. The current study shows differential effects of a maternal low quality protein diet on the offspring’s plasma amino acids. Future studies will examine further aspects of the influence of maternal low quality protein diets on fetal growth and development.

CORRELATION BETWEEN CD4 LYMPHOCYTES, VIRAL LOAD AND L-LYSINE PLASMA LEVEL IN HIV-INFECTED PATIENTS

Introduction.HIV-infection is associated with significant pathological changes of the host metabolic processes, such as energy dysfunction, dyslipidemia, protein catabolic effects and amino acid imbalance, which ultimately form the polymorphism of clinical symptoms of the disease. The significant disturbances of protein and lipid metabolism are widely described in asymptomatic and advanced stage HIV-infected patients, but infection-related amino acid abnormalities is not fully explored. The further research of HIV impact on the host metabolic processes in particular, the plasma amino acid profile, are essential for understanding the pathophysiology of HIV-infection. Our aim was to determine the association between CD4 lymphocytes, viral load and plasma L-lysine levels in clinical stages HIV-infected patients. Material and methods.A total of 750 HIV-1-infected males before highly active antiretroviral therapy (HAART) monitored in our center. The patients were classified into four stages of the disease 3, 4a, 4b and 4c, according to the classification system for HIV-infection in Russian Federation (2006). Quantitative HIV-1 RNA assay was performed using (RT-PCR) reverse-transcriptase polymerase chain reaction. The plasma L-lysine levels were assessed by thin layer chromatography (TLC). Results. We observed that plasma L-lysine concentrations markedly decreased with the clinical stages of HIV-infection. Low levels of essential amino acid were found in 57% of HIV-infected subjects in the asymptomatic stage (3), 67% and 68% in the advanced stages (4a and 4b, 4c, respectively). Our data revealed that plasma amino acid concentrations were positively correlated with CD4 count lymphocytes (P 0.01) and inversely with HIV viral load (P 0.05) in the total cohort. The mean L-lysine acid levels were significantly lower in advanced stage (4a and 4b, 4c) HIV-infected patients than in controls and asymptomatic stage (3) patients (P 0.01 and P 0.001, respectively). Conclusion. There was evidence of the association between plasma L-lysine and HIV-1 RNA level, immunological markers and clinical stages of HIV-infection among the entire cohort. The results show that advanced stages of HIV-infection are characterized by significant changes in plasma L-lysine concentrations with the disease stages of HIV-infection. Levels of this basic amino acid negatively correlating with viral load and inversely with CD4 count lymphocytes. These findings are important for understanding the pathophysiology of HIV-infection and the development of new approaches in the treatment. Although the mechanism is at present conjectural, the influence of plasma L-lysine on the HIV-1 RNA levels must be considered and remains to be proved.

Significance of Plasma Free Fatty Acid and Amino Acid Profile in Obesity-related Heart Failure

Significance of Plasma Free Fatty Acid and Amino Acid Profile in Obesity-related Heart Failure

Plasma amino acid profiles in healthy East Asian subpopulations living in Japan

ObjectivesProfiles of plasma free amino acids (PFAAs) have been utilized as biomarkers to detect various diseases. However, few studies have investigated whether ethnicity or specific subpopulations within East Asia influence PFAA concentrations.MethodsA total of 95 healthy volunteers living in Japan, including 31 Japanese individuals, 36 Korean individuals and 28 Chinese individuals, were enrolled. Participants’ PFAA levels were measured by high‐performance liquid chromatography mass spectrometry, and the effects of factors such as sex, age, body mass index (BMI) and subpopulation on PFAA profiles were analyzed.ResultsWith the exception of glutamine and α‐aminobutyric acid, there were no significant differences among the three examined subpopulations with respect to either the means or the distributions of PFAA concentrations. A multiple regression analysis revealed that most of the PFAA concentrations were significantly related to sex. Ornithine concentrations, glutamate concentrations, and glutamine and α‐aminobutyric acid concentrations were significantly associated with age, BMI, and Chinese subpopulation, respectively.ConclusionThe study results indicate that the contributions of subpopulation within East Asia to PFAA profiles are small, particularly relative to the contributions provided by sex. Am. J. Hum. Biol. 28:236–239, 2016. © 2015 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc.

Profiles of serum amino acids to screen for catabolic and inflammation status in calves with mycoplasma bronchopneumonia

Amino acid metabolism in cancer cells is significantly altered compared with that of normal cells. These changes are also reflected in the plasma amino acid profiles of patients with various types of inflammatory disease in human. Our hypothesis is that serum amino acid profiles of calves with mycoplasma Effecbronchopneumonia will be similar to those in human disease due to the inflammation and generalized catabolic state of these animals. The aim of this study was to investigate the relationships with serum amino acid profiles, total amino acids (TAA), branched amino acid:aromatic amino acid (BCAA/AAA) ratio, branched chain amino acid to tyrosine ratio (BTR) and serine to phosphorserine ratio (SPR) in calves with lung inflammation associated with mycoplasma bronchopneumonia. Receiver operative characteristic (ROC) curves was constructed to describe the performance of amino acid profiles in calves with mycoplasma bronchopneumonia. These data may be useful diagnostically and prognostically in calves with bronchopneumonia.

MON-PP031: Development of a Plasma Assay for the Bacterial ClpB Protein as a Biomarker of Eating Disorders

compared with animal-derived proteins. However, there are few data to support this contention. We assessed postprandial plasma amino acid profiles and whole-body protein synthesis following the ingestion of 35 g wheat protein hydrolysate compared with casein and whey in healthy, older males. Methods: Healthy older males (73±1 y) received a primed continuous infusion of L-[C6]-phenylalanine and L-[H2]tyrosine and ingested 35 g wheat protein hydrolysate (WHEAT; n = 12), whey (WHEY; n = 12), or micellar casein (CAS; n = 12). Plasma and muscle samples were collected at regular intervals. Repeated measures ANOVA was used to identify differences between groups over time. Results: Plasma leucine concentrations increased following protein ingestion (P < 0.01), to a similar extent following WHEAT and CAS (P = 0.86) and to a greater extent following WHEY (P < 0.01). In agreement, peak leucine concentrations averaged 351±11, 316±24, and 580±18mM for WHEAT, CAS, and WHEY, respectively (WHEAT vs CAS P = 0.40; WHEY vs WHEAT and CAS P < 0.01). Whole-body protein synthesis increased following protein ingestion in all groups (P < 0.01), with no significant differences between groups (P = 0.13). Postprandial muscle protein synthesis rates will be assessed by determining the incorporation of L-[C6]-phenylalanine into myofibrillar protein. Conclusion: Ingesting wheat protein hydrolysate increases plasma amino acid availability and stimulates whole-body protein synthesis as effectively as casein in healthy, older males.

Administration of Exogenous Growth Hormone Is Associated with Changes in Plasma and Intracellular Mammary Amino Acid Profiles and Abundance of the Mammary Gland Amino Acid Transporter SLC3A2 in Mid-Lactation Dairy Cows

The objectives of this study were to (1) identify changes in plasma and mammary intracellular amino acid (AA) profiles in dairy cows treated with growth hormone (GH), and (2) evaluate the expression of mammary gland genes involved in the transport of AA identified in (1). Eight non-pregnant (n = 4 per group) lactating dairy cows were treated with a single subcutaneous injection of either a slow-release formulation of commercially available GH (Lactotropin 500 mg) or physiological saline solution. Six days after treatment, cows were milked and blood collected from the jugular vein for the analysis of free AA in the plasma. Cows were euthanized and mammary tissue harvested. Treatment with GH increased milk, protein, fat and lactose yields, with no effect on dry matter intake. Plasma concentrations of lysine and group I AA decreased significantly, and arginine, methionine, tyrosine and arginine-family AA tended to decrease in GH-treated cows. Concentrations of intracellular glycine, serine and glutamate increased significantly, with a trend for decreased arginine observed in the mammary gland of GH-treated cows. A trend for increased concentrations of intracellular total AA, NEAA and arginine-family AA were observed in the mammary gland of GH-treated cows. Variance in the concentration of plasma methionine, tyrosine, valine, alanine, ornithine, BCAA, EAA was significantly different between treatments. Variance in the concentration of intracellular lysine, valine, glutamine, EAA and group II was significantly different between treatments. AA changes were associated with increased mRNA abundance of the mammary gland AA transporter SLC3A2. We propose that these changes occur to support increased milk protein and fatty acid production in the mammary gland of GH-treated cows via potential mTOR pathway signaling.

Role of amino acids in the pathophysiology of autism spectrum disorders in Saudi and Egyptian population samples

Autism spectrum disorders are complex developmental disorders with increasing incidence and poorly understood etiology. Imbalance of amino acids profoundly influences brain function, and is thought to be one of the key players in the pathophysiology of autism. This study aimed to measure the plasma amino acid profiles of 20 Egyptian and 20 Saudi autistic patients in comparison to matching healthy controls to clarify the role of impaired amino acid concentrations in the etiology of autism. Plasma amino acids profiles were measured using high performance liquid chromatography. While plasma levels of glutamic, aspartic, and glycine recorded the most significant percentage elevated amino acids, glutamine, asparagine, arginine, tyrosine and isoleucine recorded the most remarkable percentage decrease in autistic patients from both populations compared to controls. Among the calculated relative values, only acidic/basic, and glutamate/glutamine ratios were significantly higher in autistics compared to controls. Non-essential/essential and glucogenic/ketogenic ratios were unaltered in autistics compared to controls. Increased plasma glutamate/glutamine ratio, together with increased glycine, arginine, aspartate, aspargine levels, and acidic/basic amino acid ratio can serve as a predictive tools for the early detection of autism. These findings suggest that glu- tamatergic abnormalities in the brain may be associated with the pathobiology of autism.

Extruded soybean meal increased feed intake and milk production in dairy cows

The objective of this study was to assess the effects of 2 extruded soybean meals (ESBM) processed at 2 extruder temperatures, 149°C (LTM) and 171°C (HTM), on performance, nutrient digestibility, milk fatty acid and plasma amino acid profiles, and rumen fermentation in lactating dairy cows. Nine multiparous Holstein cows were included in a replicated 3×3 Latin square design experiment with three 28-d periods. The control diet contained 13% solvent-extracted soybean meal (SSBM; 53.5% crude protein with 74.1% ruminal degradability and 1.8% fat), which was replaced with equivalent amount (dry matter basis) of LTM (46.8%, 59.8%, and 10.0%) or HTM (46.9%, 41.1%, and 10.9%, respectively) ESBM in the 2 experimental diets (LTM and HTM, respectively). The diets met or exceeded the nutrient requirements of the cows for net energy of lactation and metabolizable protein. The 2 ESBM diets increased dry matter intake and milk yield compared with SSBM. Feed efficiency and milk composition were not affected by treatment. Milk protein yield tended to be increased by ESBM compared with SSBM. Milk urea N and urinary urea N excretions were increased by the ESBM diets compared with SSBM. Concentration of fatty acids with chain length of up to C17 and total saturated fatty acids in milk fat were generally decreased and that of C18 and total mono- and polyunsaturated fatty acids was increased by the ESBM diets compared with SSBM. Blood plasma concentrations of His, Leu, and Val were increased by HTM compared with LTM and SSBM. Plasma concentration of Met was decreased, whereas that of carnosine was increased by the ESBM diets. Treatments had no effect on rumen fermentation, but the proportion of Fibrobacter spp. in whole ruminal contents was increased by HTM compared with SSBM and LTM. Overall, data from this crossover experiment suggest that substituting SSBM with ESBM in the diet has a positive effect on feed intake and milk yield in dairy cows.

High Protein Intake Does Not Prevent Low Plasma Levels of Conditionally Essential Amino Acids in Very Preterm Infants Receiving Parenteral Nutrition.

We have shown that increasing protein intake using a standardized, concentrated, added macronutrients parenteral (SCAMP) nutrition regimen improves head growth in very preterm infants (VPIs) compared with a control parenteral nutrition (PN) regimen. VPIs are at risk of conditionally essential amino acid (CEAA) deficiencies because of current neonatal PN amino acid (AA) formulations. We hypothesized that the SCAMP regimen would prevent low plasma levels of CEAAs. To compare the plasma AA profiles at approximately day 9 of life in VPIs receiving SCAMP vs a control PN regimen. VPIs (<29 weeks' gestation) were randomized to receive SCAMP (30% more PN AA) or a control regimen. Data were collected to measure parenteral and enteral protein, energy, and individual AA intake and the first plasma AA profile. Plasma profiles of the 20 individual protogenic AA levels were measured using ion exchange chromatography. Plasma AA profiles were obtained at median (interquartile range [IQR]) age of 9 (8-10) days in both SCAMP (n = 59) and control (n = 67) groups after randomizing 150 VPIs. Median (IQR) plasma levels of individual essential AAs were higher than the reference population mean (RPM) in both groups, especially for threonine. SCAMP infants had higher plasma levels of essential AAs than did the controls. Median (IQR) plasma levels of glutamine, arginine, and cysteine (CEAAs) were lower than the RPM in both groups. Plasma AA levels in PN-dependent VPIs indicate there is an imbalance in essential and CEAA provision in neonatal PN AA formulations that is not improved by increasing protein intake.

Association between insulin resistance and plasma amino acid profile in non-diabetic Japanese subjects.

Aims/IntroductionElevation of the branched-chain amino acids (BCAAs), valine, leucine and isoleucine; and the aromatic amino acids, tyrosine and phenylalanine, has been observed in obesity-related insulin resistance. However, there have been few studies on Asians, who are generally less obese and less insulin-resistant than Caucasian or African-Americans. In the present study, we investigated the relationship between homeostasis model assessment of insulin resistance (HOMA-IR) and plasma amino acid concentration in non-diabetic Japanese participants.Materials and MethodsA total of 94 healthy men and women were enrolled, and plasma amino acid concentration was measured by liquid chromatography/mass spectrometry after overnight fasting. The associations between HOMA-IR and 20 amino acid concentrations, and anthropometric and clinical parameters of lifestyle-related diseases were evaluated.ResultsThe mean age and body mass index were 40.1 ± 9.6 years and 22.7 ± 3.9, respectively. Significantly positive correlations were observed between HOMA-IR and valine, isoleucine, leucine, tyrosine, phenylalanine and total BCAA concentration. Compared with the HOMA-IR ≤ 1.6 group, the HOMA-IR > 1.6 group showed significantly exacerbated anthropometric and clinical parameters, and significantly elevated levels of valine, isoleucine, leucine, tyrosine, phenylalanine and BCAA.ConclusionsThe present study shows that the insulin resistance-related change in amino acid profile is also observed in non-diabetic Japanese subjects. These amino acids include BCAAs (valine, isoleucine and leucine) and aromatic amino acids (tyrosine and phenylalanine), in agreement with previous studies carried out using different ethnic groups with different degrees of obesity and insulin resistance.

Tryptophan provision by dietary supplementation of a Bacillus subtilis mutant strain in piglets

Supplementing Bacillus (B.) subtilis mutants selected to overproduce a specific amino acid (AA) may be an alternative method to provide essential AA in pig diets. Two experiments on a B. subtilis strain selected to overproduce Trp were conducted using 8-kg pigs fed Trp-deficient diets for 20 d. B. subtilis were supplied in a low or high dose in Experiments 1 and 2, respectively. The Trp-deficient diet (0.15 SID Trp:Lys) reduced (p < .05) both gain and feed intake of piglets compared to the positive control diet (0.17 SID Trp:Lys). Supplementation of the B. subtilis strain was not able to counterbalance the Trp deficiency in any of the two experiments. No effect of B. subtilis supplementation to piglet diets was observed on the plasma AA profile. In conclusion, this mutant strain of B. subtilis was not able to compensate a Trp deficiency in the tested doses.

Plasma Metabolomics Reveal Longitudinal Changes in Branched‐Chain Amino Acids and other Metabolites during Diabetes Progression in the UCD‐Type‐2‐Diabetes Rat Model

Type 2 diabetes mellitus (T2D) causes dysregulation in many metabolic pathways; however, temporal progression of these disturbances has not been fully elucidated. Alterations of branched‐chain amino acids (BCAAs) have been implicated in the diabetes phenotype, but cause‐effect is not established. Using a model that closely resembles T2D in humans, the UCD‐T2DM rat, we utilized metabolomics to assess plasma metabolites in pre‐diabetic rats and after the onset of diabetes at 2‐, 12, and 24 weeks. Partial least squares‐discriminant analysis (PLS‐DA) identified a high number of amino acids that were decreased in plasma at 12‐ and 24‐weeks relative to pre‐diabetic rats. Increased leucine and isoleucine plasma abundances were identified in 24 week diabetic rats only. Plasma BCAAs were inversely related to the decline in the total body weight as diabetes progressed over time. All other amino acids decreased in parallel with the decline in total body weight. TCA cycle intermediates, phenols and glucose derivatives were increased by diabetes at 12‐ and 24‐weeks. These observations indicate that the association between plasma BCAAs and T2D is apparent after the onset of the disease phenotype; thus, a result of T2D. Associations between amino acids and weight suggest that the plasma amino acid profile tracks catabolic changes associated with T2D. Additional metabolites that may provide biomarkers of diabetes progression will also be presented.

Abstract P150: Weight-Loss Diets and 2-Year Change of Circulating Amino Acids in Two Randomized Intervention Trials

Background: Emerging evidence has related circulating amino acids to diabetes and cardiovascular risk. Little is known about how diet modifications affect circulating amino acids. The present study aimed to examine the effects of weight-loss diets on long-term changes in plasma amino acids, and their relations with weight loss and metabolic outcomes. Methods and Results: We repeatedly measured plasma amino acid profiles over 2 years among overweight or obese participants from two randomized dietary interventional weight-loss trials: 774 from the Preventing Overweight Using Novel Dietary Strategies trial (POUNDS LOST) and 318 from Dietary Intervention Randomized Controlled Trial (DIRECT). The plasma levels of most amino acids decreased from baseline during follow-up in both trials. In the POUNDS LOST trial, compared to the high-protein diets, the average-protein weight-loss diets showed a greater effect on decreasing plasma levels of a diabetes-associated branched-chain amino acid (BCAA) valine and another amino acid methyl-histidine at 6 months, independent of weight change (p&lt;0.002). Furthermore, the changes of plasma BCAA leucine/isoleucine, aromatic amino acid tyrosine and phenylalanine, and four other amino acids (alanine, sarcosine, hydroxyproline, and methionine) were positively related to concurrent weight loss, consistently in both trials (5-13g weight loss per 1 unit decease in log[amino acid in μmol/L], p&lt;0.002). Moreover, the changes in tyrosine and alanine were positively related to changes in insulin resistance, independent of weight change, in both trials (p&lt;0.05). Conclusion: Our findings underscore the potential importance of weight-loss dietary interventions in improvement of amino acid profiles and related cardiometabolic risk.

Plasma branched-chain and aromatic amino acid concentration after ingestion of an urban or rural diet in rural Mexican women.

BackgroundPeople living in rural areas are prone to move to urban cities experiencing a dramatic change in the type of protein consumed. However, it is not know if those changes are associated with changes in the plasma amino acid concentration, especially the branched chain amino acids. Thus, the aim of the present study was to evaluate, in a rural Mexican population, the plasma amino acid profile after consumption of typical Mexican rural or urban diet.ResultsWe evaluated the plasma amino acid concentrations of women from a rural population at 0, 30, 60, 90, 120, 180 and 240 min after ingestion of a typical Mexican rural or urban diet. Ingestion of a Mexican urban diet induced a higher increase in leucine, isoleucine, valine, phenylalanine, tyrosine and proline than ingestion of a Mexican rural diet in women from a Mexican rural population. Arginine, histidine, lysine, threonine, alanine, glycine and serine had the same area under the curve regardless of the experimental diet.ConclusionsIngestion of a Mexican urban diet induced a higher increase in leucine, isoleucine, valine, phenylalanine, tyrosine and proline than ingestion of a Mexican rural diet in women from a Mexican rural area.

Plasma amino acid profiling identifies specific amino acid associations with cardiovascular function in patients with systolic heart failure.

BackgroundThe heart has close interactions with other organs’ functions and concomitant systemic factors such as oxidative stress, nitric oxide (NO), inflammation, and nutrition in systolic heart failure (HF). Recently, plasma amino acid (AA) profiling as a systemic metabolic indicator has attracted considerable attention in predicting the future risk of human cardiometabolic diseases, but it has been scarcely studied in HF.MethodsThirty-eight stable but greater than New York Heart Association class II symptomatic patients with left ventricular (LV) ejection fraction <45% and 33 asymptomatic individuals with normal B-type natriuretic peptide (BNP) value were registered as the HF and control groups, respectively. We analyzed fasting plasma concentrations of 41 AAs using high-performance liquid chromatography, serum NO metabolite concentration, hydroperoxide and high-sensitivity C-reactive protein measurements, echocardiography, and flow-mediated dilatation.ResultsWe found that 17 AAs and two ratios significantly changed in the HF group compared with those in the control group (p < 0.05). In the HF group, subsequent univariate and stepwise multivariate analyses with clinical variables revealed that Fischer ratio and five specific AAs, ie, monoethanolamine, methionine, tyrosine, 1-methylhistidine, and histidine have significant correlation with BNP, LV ejection fraction, LV end-diastolic volume index, inferior vena cava diameter, the ratio of early diastolic velocity of the mitral inflow to mitral annulus, and BNP, respectively (p < 0.05). Interestingly, further exploratory factor analysis categorized these AAs into hepatic-related (monoethanolamine, tyrosine, and Fischer ratio) and skeletal muscle-related (histidine, methionine, and 1-methylhistidine) components. Some categorized AAs showed unique correlations with concomitant factors: monoethanolamine, tyrosine, and Fischer ratio with serum NO concentration; histidine with serum albumin; and 1-methylhistidine with flow-mediated dilatation (p < 0.05).ConclusionsPlasma AA profiling identified correlations of specific AAs with cardiac function and concomitant factors, highlighting the cardio-hepatic-skeletal muscle axis in patients with systolic HF.

A New Mouse Model of Mild Ornithine Transcarbamylase Deficiency (spf-j) Displays Cerebral Amino Acid Perturbations at Baseline and upon Systemic Immune Activation

Ornithine transcarbamylase deficiency (OTCD, OMIM# 311250) is an inherited X-linked urea cycle disorder that is characterized by hyperammonemia and orotic aciduria. In this report, we describe a new animal model of OTCD caused by a spontaneous mutation in the mouse Otc gene (c.240T>A, p.K80N). This transversion in exon 3 of ornithine transcarbamylase leads to normal levels of mRNA with low levels of mature protein and is homologous to a mutation that has also been described in a single patient affected with late-onset OTCD. With higher residual enzyme activity, spf-J were found to have normal plasma ammonia and orotate. Baseline plasma amino acid profiles were consistent with mild OTCD: elevated glutamine, and lower citrulline and arginine. In contrast to WT, spf-J displayed baseline elevations in cerebral amino acids with depletion following immune challenge with polyinosinic:polycytidylic acid. Our results indicate that the mild spf-J mutation constitutes a new mouse model that is suitable for mechanistic studies of mild OTCD and the exploration of cerebral pathophysiology during acute decompensation that characterizes proximal urea cycle dysfunction in humans.

Metabolomics Approach Reveals Altered Plasma Amino Acid and Sphingolipid Profiles Associated with Patholological State in Transition Dairy Cows

Every other cow in a dairy herd is affected by one or multiple diseases during the periparturient period; however, the reason for this high incidence rate of diseases is not clear yet. The objective of this study was to evaluate whether diseased cows show alterations in the amino acid and sphingolipid profiles around calving. Transition dairy cows affected by multiple periparturient diseases (n=6) and healthy controls (n=6) were selected to quantify amino acid and sphingolipid components in the plasma at 4 time points (-4, -1, +1, and +4 wks) around parturition. Samples were sorted retrospectively and analyzed by DI-MS/MS. Univariate and multivariate data analyses were performed at each time point to elucidate the relationship between metabolite alterations and disease progression. Results from the univariate ananlysis indicated increased concentrations of multiple plasma amino acids in the sick cows as compared to healthy controls at -4 wk before parturition. At -1 wk before parturition marked elevations of sphingolipids occured in the sick cows. During the week of parturition very minor differences in amino acid and sphingolipid profiles were observed between healthy and sick cows. However, at +4 wk after parturion a marked decrease in various amino acid and sphingolipid compounds were observed in cows with health problems. Multivariate analysis also classified the sick and healthy cows on the basis of plasma amino acid profiles at -4 wk before calving. In conclusion, altered profiles of plasma amino acids and sphingolipids in the sick cows during the transition period suggest an association among disease state and the dynamics of amino acid and sphingolipid metabolism giving insight on the etiopathology of the disease state. Moreover, this suggests utilization of selected amino acids as biomarkers for disease or deviations from normal state of health.

Plasma amino acid profiling in major depressive disorder treated with selective serotonin reuptake inhibitors.

Amino acids are important body metabolites and seem to be helpful for understanding pathogenesis and predicting therapeutic response in major depressive disorder (MDD). We performed amino acid profiling to discover potential biomarkers in major depressive patients treated with selective serotonin reuptake inhibitors (SSRIs). Amino acid profiling using aTRAQ™ kits for Amino Acid Analysis in Physiological Fluids on a liquid chromatography-tandem mass spectrometry (LC-MS/MS) system was performed on 158 specimens at baseline and at 6 weeks after the initiation of SSRI treatment for 68 patients with MDD and from 22 healthy controls. Baseline alpha-aminobutyric acid (ABA) discriminated the patients according to the therapeutic response. Plasma glutamic acid concentration and glutamine/glutamic acid ratio were different between before and after SSRI treatment only in the response group. Comparing patients with MDD with healthy controls, alterations of ten amino acids, including alanine, beta-alanine, beta-aminoisobutyric acid, cystathionine, ethanolamine, glutamic acid, homocystine, methionine, O-phospho-L-serine, and sarcosine, were observed in MDD. Metabolism of amino acids, including ABA and glutamic acid, has the potential to contribute to understandings of pathogenesis and predictions of therapeutic response in MDD.