Plasma Free Amino Acid Profiles Research Articles

Common alterations in plasma free amino acid profiles and gut microbiota-derived tryptophan metabolites of five types of cancer patients.

Amino acids not only play a vital role in the synthesis of biological molecules such as proteins in cancer malignant cells, they are also essential metabolites for immune cell activation and antitumor effects in the tumor microenvironment. The abnormal changes in amino acid metabolism are closely related to the occurrence and development of tumors and immunity. Intestinal microorganisms play an essential role in amino acid metabolism, and tryptophan and its intestinal microbial metabolites are typical representatives. However, it is known that the cyclic amino acid profile is affected by specific cancer types, so relevant studies mainly focus on one type of cancer and rarely study different cancer forms at the same time. The objective of this study was to examine the PFAA profile of five cancer patients and the characteristics of tryptophan intestinal microbial metabolites to determine whether there are general amino acid changes across tumors. Plasma samples were collected from esophageal (n = 53), lung (n = 73), colorectal (n = 94), gastric (n = 55), breast cancer (n = 25), and healthy control (HC) (n = 139) subjects. PFAA profile and tryptophan metabolites were measured, and their perioperative changes were examined using high-performance liquid chromatography. Univariate analysis revealed significant differences between cancer patients and HC. Furthermore, multivariate analysis discriminated cancer patients from HC. Regression diagnosis models were established for each cancer group using differential amino acids from univariate analysis. Receiver-operating characteristic analysis was applied to evaluate these diagnosis models. Finally, GABA, arginine, tryptophan, taurine, glutamic acid, and melatonin showed common alterations across all types of cancer patients. Metabolic pathway analysis shows that the most significant enrichment pathways were tryptophan, arginine, and proline metabolism. This study provides evidence that common alterations of the metabolites mentioned above suggest their role in the pathogenesis of each cancer patient. It was suggested that multivariate models based on PFAA profiles and tryptophan metabolites might be applicable in the screening of cancer patients.

Plasma free amino acid profiles are associated with serum high molecular weight adiponectin levels in Japanese medical check-up population without type 2 diabetes mellitus

To prevent the progression of type 2 diabetes mellitus (T2DM), early detection and intervention are important. Several studies have already shown that the serum adiponectin level could be useful for evaluating the future risk of T2DM. Recently, plasma free amino acid (PFAA) concentrations have also emerged as potential biomarkers that predict the future onset of T2DM. In this study, we aimed to further characterise PFAA profiles by elucidating the association with the serum high molecular weight (HMW) adiponectin level in this cross-sectional study. A total of 1000 Japanese subjects who underwent medical check-ups were enrolled, and their plasma concentrations of 21 amino acids and clinical parameters were measured. The subjects without T2DM were divided into quartiles (Q1-4) by serum HMW adiponectin level, and the association with between PFAA concentrations was analysed. Concentrations of glutamate, alanine, proline, tyrosine, histidine, methionine, lysine, branched-chain amino acids (BCAAs) and tryptophan varied significantly according to the adiponectin quartile. Furthermore, serum adiponectin levels showed significant inverse correlations with these amino acids. The change in the PFAA profile in the group with the lowest adiponectin concentrations (Q1) was similar to that of T2DM patients. Although both adiponectin levels and PFAA concentrations are known to be altered by the accumulation of visceral fat and insulin resistance, the levels of glutamate, BCAA, lysine and tryptophan remain significantly associated with adiponectin level after adjustment for age, body mass index and homeostasis model assessment of insulin resistance, showing the direct association between PFAA concentrations and the serum HMW adiponectin level. Registration number: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) UMIN000029920, registered on Nov 13th 2017 (prospectively registered).

Decreased circulating branched-chain amino acids are associated with development of Alzheimer's disease in elderly individuals with mild cognitive impairment.

Nutritional epidemiology has shown that inadequate dietary protein intake is associated with poor brain function in the elderly population. The plasma free amino acid (PFAA) profile reflects nutritional status and may have the potential to predict future changes in cognitive function. Here, we report the results of a 2-year interim analysis of a 3-year longitudinal study following mild cognitive impairment (MCI) participants. In a multicenter prospective cohort design, MCI participants were recruited, and fasting plasma samples were collected. Based on clinical assessment of cognitive function up to 2 years after blood collection, MCI participants were divided into two groups: remained with MCI or reverted to cognitively normal ("MCI-stable," N = 87) and converted to Alzheimer's disease (AD) ("AD-convert," N = 68). The baseline PFAA profile was compared between the two groups. Stratified analysis based on apolipoprotein E ε4 (APOE ε4) allele possession was also conducted. Plasma concentrations of all nine essential amino acids (EAAs) were lower in the AD-convert group. Among EAAs, three branched-chain amino acids (BCAAs), valine, leucine and isoleucine, and histidine (His) exhibited significant differences even in the logistic regression model adjusted for potential confounding factors such as age, sex, body mass index (BMI), and APOE ε4 possession (p < 0.05). In the stratified analysis, differences in plasma concentrations of these four EAAs were more pronounced in the APOE ε4-negative group. The PFAA profile, especially decreases in BCAAs and His, is associated with development of AD in MCI participants, and the difference was larger in the APOE ε4-negative population, suggesting that the PFAA profile is an independent risk indicator for AD development. Measuring the PFAA profile may have importance in assessing the risk of AD conversion in the MCI population, possibly reflecting nutritional status. [https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000025322], identifier [UMIN000021965].

Characteristic changes in plasma glutamate levels and free amino acid profiles in Japanese patients with type 1 diabetes mellitus.

In addition to absolute insulin deficiency, dysregulated glucagon in type 1 diabetes is considered pathophysiologically important. Previously, we confirmed the presence of dysregulated glucagon in Japanese patients with type 1 diabetes, and found a significant correlation between plasma glucagon and blood urea nitrogen levels, suggesting an association between glucagon and amino acid metabolism. In this study, we evaluated plasma amino acid levels in Japanese patients with type 1 diabetes in the context of their functional relationship with glucagon. We assessed plasma free amino acid levels using liquid chromatography-mass spectrometry in 77 Japanese patients with type 1 diabetes, and statistically analyzed their characteristics and relationships with clinical parameters, including glucagon. Participants with type 1 diabetes showed a large decrease in glutamate levels together with a characteristic change in plasma free amino acid profiles. The network structural prediction analyses showed correlations between each amino acid and glucagon in type 1 diabetes. Participants with type 1 diabetes showed characteristic changes in plasma glutamate levels and free amino acid profiles compared with controls and type 2 diabetes patients. Glucagon showed a closer correlation with amino acids than with parameters of glucose metabolism, suggesting that type 1 diabetes includes dysregulation in amino acids through dysregulated glucagon from remaining pancreatic α-cells, together with that in glucose by insulin deficiency.

Associations of AminoIndex Cancer Screening (Breast) Grade with Clinical and Laboratory Variables

Altered metabolism in the blood of cancer patients is closely related to changes in amino acids. Amino acids play an important physiological role as essential metabolites and regulators of metabolism. AminoIndex Cancer Screening (AICS) uses multivariate analysis of plasma-free amino acid profiles to screen for seven cancer types, including breast cancer.To determine the clinical utility of AICS (breast), we retrospectively analyzed associations of AICS (breast) score with clinical and laboratory variables in 390 patients who underwent AICS (breast) testing. The mean age of participants was 50.7 years (range: 26-87 years) and all were female.The AICS (breast) grade was A, B, and C for 250 (64.1%), 90 (23.1%), and 50 (12.8%) participants, respectively. AICS (breast) was significantly correlated with AICS (gastric) (r = 0.487, p < 0.0001) and AICS (lung) (r = 0.523, p < 0.0001). Multivariate linear regression analysis showed no significant difference of AICS (breast) grade with age, body mass index, estimated glomerular filtration rate, dyslipidemia, or blood pressure. However, neutrophil-to-lymphocyte ratio significantly differed in relation to AICS (breast) grade (cut-off value, 1.7; p = 0.030), although only data from 72 patients were analyzed.To our knowledge, this is the first study to report associations of AICS (breast) grade with clinical variables.

Guanidine acetic acid supplementation altered plasma and tissue free amino acid profiles in finishing pigs

BackgroundAs a nutritive feed additive, guanidine acetic acid (GAA) participates in the metabolism of energy and proteins. This study aimed to investigate the effects of GAA on growth performance, organ index, plasma and tissue free amino acid profiles, and related metabolites in finishing pigs. A total of 72 crossbred pigs (body weight 86.59 ± 1.16 kg) were randomly assigned to 1 of 4 dietary treatments (GAA0, GAA500, GAA1000, and GAA1500). They were fed the basal diets supplemented with 0, 500, 1000, or 1500 mg/kg GAA for 42 days, respectively. The growth performance and organ weight were evaluated, and the contents of crude protein, free amino acids, and metabolites in plasma and tissues were determined. Spearman correlation between plasma and tissue free amino acids and related metabolites was also analyzed.ResultsGrowth performance in pigs was not altered by GAA (P > 0.05). The absolute and relative weight of kidneys increased (quadratic, P < 0.05). As dietary GAA concentration was increased, the contents of plasma glycine, serine, leucine, ornithine, and ratio of ornithine/arginine decreased (linear or quadratic, P < 0.05), but the contents of plasma isoleucine and taurine and the ratios of alanine/branched-chain amino acids and proline/ornithine increased quadratically (P < 0.05). The hepatic γ-amino-n-butyric acid content increased linearly and quadratically (P < 0.001), while the carnosine content decreased (quadratic, P = 0.004). The contents of renal arginine, proline, cystine, glutamate, and total amino acids (TAA) decreased quadratically (P < 0.05), but the contents of glycine (quadratic, P = 0.015) and γ-amino-n-butyric acid (linear, P = 0.008) increased. The pancreatic tryptophan content (quadratic, P = 0.024) increased, while the contents of pancreatic proline (linear, P = 0.005) and hydroxyproline (quadratic, P = 0.032) decreased in response to GAA supplementation. The contents of cardiac essential amino acids (EAA), nonessential amino acids (NEAA), and TAA in GAA1000 were higher than those in GAA1500 (P < 0.05). Supplementing with GAA linearly increased the contents of methionine, threonine, valine, isoleucine, leucine, phenylalanine, tryptophan, lysine, histidine, arginine, serine, alanine, glutamine, asparagine, tyrosine, proline, taurine, cystathionine, α-aminoadipic acid, β-aminoisobutyric acid, EAA, NEAA, and TAA in the spleen (P < 0.05). A strong Spearman correlation existed between plasma and tissue free amino acids and related metabolites.ConclusionGAA supplementation did not altered pig growth performance, but it altered plasma and tissue free amino acid profiles and the contents of related metabolites in pigs in a tissue-dependent manner.

Development of a Novel Nutrition-Related Multivariate Biomarker for Mild Cognitive Impairment Based on the Plasma Free Amino Acid Profile.

Nutritional epidemiology has shown the importance of protein intake for maintaining brain function in the elderly population. Mild cognitive impairment (MCI) may be associated with malnutrition, especially protein intake. We explored blood-based biomarkers linking protein nutritional status with MCI in a multicenter study. In total, 219 individuals with MCI (79.5 ± 5.7 year) from 10 institutions and 220 individuals who were cognitively normal (CN, 76.3 ± 6.6 year) in four different cities in Japan were recruited. They were divided into the training (120 MCI and 120 CN) and validation (99 MCI and 100 CN) groups. A model involving concentrations of PFAAs and albumin to discriminate MCI from CN individuals was constructed by multivariate logistic regression analysis in the training dataset, and the performance was evaluated in the validation dataset. The concentrations of some essential amino acids and albumin were significantly lower in MCI group than CN group. An index incorporating albumin and PFAA discriminated MCI from CN participants with the AUC of 0.705 (95% CI: 0.632–0.778), and the sensitivities at specificities of 90% and 60% were 25.3% and 76.8%, respectively. No significant association with BMI or APOE status was observed. This cross-sectional study suggests that the biomarker changes in MCI group may be associated with protein nutrition.

The use of metabolomics tools in the evaluation of the fattening performance of lambs

This study aimed to determine the metabolomic characteristics associated with the fattening performance of the Awassi lamb breed under intensive fattening for 90 days. Twenty-four lambs were used in the research. The lambs were divided into two groups according to their fattening performance (good fattening performance, n = 12, and poor fattening performance, n = 12), and their metabolomic properties were evaluated. The differences between the two research groups in the amino acids of alloisoleucine, aspartic acid, histidine, hydroxylysine, isoleucine, lysine, methionine, phenylalanine, tryptophan, valine, and 1-methylhistidine were found to be statistically significant (P ≤ 0.001). Moderately significant negative correlations were found between daily concentrate feed intake and 3-methylhistidine (r = −0.469; P = 0.021), hydroxylysine (r = −0.408; P = 0.048), and serotonin (r= −0.467; P = 0.021); as well as between the average daily weight gain (ADWG) and alloisoleucine (r = −0.528; P = 0.008), 3-methylhistidine (r = −0.440; P = 0.032), and hydroxylysine (r = −0.577; P = 0.003). A moderate positive correlation was found between hydroxyisovalerylcarnitine and ADWG (r = 0.476; P = 0.019), and a negative correlation was found between hydroxyisovalerylcarnitine and the feed conversion ratio (r = −0.430; P = 0.036). Pathway analysis revealed that the most important biological pathway was the phenylalanine, tyrosine, and tryptophan biosynthesis pathway. The results of the research reveal the potential for plasma free amino acid and carnitine profiles to be used as candidate biomarkers in the evaluation of fattening performance in lambs.

Relationship between plasma free amino acid profiles and changes in Crohn’s disease activity index after administration of an elemental diet in patients with Crohn’s disease

Purpose: We aimed to elucidate the relationship between plasma free amino acid profiles and changes in the Crohn’s disease activity index (CDAI) among patients with Crohn’s disease (CD) after administration of an elemental diet (ED). Patients and methods: We measured fasting plasma concentrations of free amino acids in 5 patients with CD and evaluated the relationship between amino acid concentration and disease activity at 4 weeks after administration of an ED. Results: Concentrations of valine, lysine, tyrosine, and glutamic acid were significantly increased after administration of an ED. Significant correlations were noted between changes in CDAI scores and valine concentrations. Tryptophan concentrations also exhibited a strong correlation with CDAI scores. Conclusion: In patients with CD, plasma concentrations of valine and tryptophan appear to be associated with disease activity following treatment with an ED.

Cancer risk screening based on plasma free amino acid profiles

Cancer risk screening based on plasma free amino acid profiles

Clinical correlation of plasma amino acid profile of post-surgical gastric cancer patients and metastatic gastric cancer patients for establishing biomarker of metastasis

Objectives: This research is aimed to evaluate plasma free amino acid in gastric cancer patients without metastasis (early gastric cancer post gastrectomy) and with metastasis (advanced gastric cancer). Amino acids level of postoperative gastric cancer (M0) patients are compared with metastatic gastric cancer (M1) patients in search of biomarker which can predict the metastasis of gastric cancer. We have made clinical correlation of patients’ vital signs, respiratory rate, pulse rate, blood pressure, body temperature, disease stages, chief complaints, complications and survival curve within light of metastatic and nonmetastatic domain. Background: Majority of cancer patients are diagnosed after seeding of metastatic cells to adjacent organs and distant sites. At this point, treatment is palliative and supportive. The cellular propagation of cancer cells and tumor micro-environment plays vital role in genesis of gastric cancer. Genetic alteration leading to faulty nucleotides to amino acids, then to protein, and finally formation of tumor is the natural sequence of pathogenesis of gastric cancer. Prediction of metastasis by use of plasma free amino acid profile may be of great significance because it will help to tailor the patient specific cancer treatment. Plasma Amino acids are ideal for being developed as tool for prediction of metastasis as they are affordable, less expensive and convenient. Method: This study includes total 54 patients, among which 27 had metastasis of Gastric cancer and rest 27 had undergone gastric surgery at early stage with no recurrence at the time of the study. Twenty-three amino acids were studied. Student’s t test was performed to find out statistically significant values of amino acids. The p value of ≤ 0.05 was considered statistically significant. Amino acids with significant p values were investigated with multivariate logistic regression. Partial Least Squares Discriminant Analysis (PLS DA) was done using Microsoft SPSS 23 version software®. Variable Importance of Projection (VIP) was estimated, values ≥ 1 was considered statistically significant. Result: Performance Score (PS) (p= 0.004) and Body Mass Index (BMI) (p= 0.035) were statistically significant between M0 and M1 groups. Staging (I, II vs. III, IV) (p&lt; 0.001) was significant. Seven amino acids, Asp, Cys, Hcy, His, Leu, Orn and Ser were significant between M0 and M1 in first month evaluation. Eight amino acids, Cys, Hcy, His, Leu, Met, Thr, Trp and Tyr were significant between M0 and M1 in sixth month evaluation. PLS DA regression analysis, VIP test showed Cys, Ser, Hcy, Thr, His, Met, Tyr, Trp to be more important amino acids of significance. Kaplan Meier Overall Survival (OS) = 34.979 months. Mean survival time in M0 was 43.53± 1.741 months. Mean survival in M1 was 26.29± 2.635 months. Conclusion: We found BMI and PS as most important variables in defining and determining the disease status of gastric cancer patients. Nutrition and physical activity is very much characteristic of disease outcome from a physician’s perspective. This study propounds amino acids can be valuable biomarkers of predictive and prognostic importance in metastasis in gastric cancer patients.

A Pilot Study for Investigation of Plasma Amino Acid Profile in Neurofibromatosis Type 1 Patients.

Neurofibromatosis, also known as Von Recklinghausen disease, is a systemic and progressive genetic disease that primarily affects the skin, eyes, nervous system, and bones. The disease can occur in a variety of ways and can vary in individuals. Metabolomic-based research using blood samples has enabled new diagnostic methods to be used in the diagnosis of various diseases, especially cancer. Among the metabolites, profiling of plasma free amino acids (PFAA) is a promising approach because PFAAs bind all organ systems and play an important role in the metabolism. This study aimed to determine the characteristics of PFAA profiles in neurofibromatosis patients and the possibility of using them for early detection and treatment of the disease. Patients with a diagnosis of Neurofibromatosis Type I confirmed by genetic analysis and healthy individuals of the same age group without any disease were included in the study. We analysed the nineteen plasma free amino acids (phenylalanine, proline, threonine, arginine, asparagine, cystine, valine, glutamate, tyrosine, serine, glutamine, glycine, tryptophane, leucine, lysine, methionine, isoleucine, aspartate and alanine) from neurofibromatosis Type I patients and control group by liquid chromatography tandem mass spectrometry (LC-MS/MS) in Metabolism Laboratory of Harran University Research and Application Hospital. The results of the plasma free amino acid levels were divided into 3 groups as essential, semi-essential, and non-essential. The differences in amino acid levels between groups were determined. The levels of eight amino acids (methionine, arginine, cystine, glutamine, proline, asparagine, serine, aspartate) were significantly altered in patients with neurofibromatosis type 1. In essential amino acids, methionine levels were significantly higher in the patient group than control group. While the levels of arginine and glutamine in semi-essential amino acids were statistically significantly higher in the patient group, a significant decrease was observed in cystine and proline levels compared to the control group's amino acid levels. In the non-essential amino acids group, asparagine, serine and aspartate amino acid levels were significantly higher in the patient group compared to the control group. The current research predicates that eight amino acids, namely methionine, arginine, cystine, glutamine, proline, asparagine, serine, aspartate can be considered to be valuable biomarkers for neurofibromatosis type I. This present study is the first to build models for neurofibromatosis Type I screening using plasma free amino acids and the amino acid profile will be able to guide the prediction of the complications that may occur during the course of the disease.

Amino Acids Profile and Vitamin D Measurement in Hypertension in Egyptian Population

Objective: To investigate the association between plasma free amino acids (PFAAs) profile changes, vitamin D concentration and hypertension and evaluate the clinical utility of this association for nascent hypertension before the development of complications.&#x0D; Methods: 70 subjects were enrolled in this study; 50 of them were hypertensive (25 were with uncontrolled hypertensive and 25 were with controlled hypertensive), the other 20 subjects were healthy controls.&#x0D; Results: Circulating levels of Branched chain amino acids (BCAAs); (valine, leucine, and isoleucine), Aromatic amino acids (AAAs); (phenylalanine, tyrosine, and tryptophan), homocysteine, aspartic, ornithine, asparagine and lysine were elevated significantly in both uncontrolled and controlled hypertensive subgroups in comparison with control group. On the contrary, the results showed marked decline in the concentration of threonine, serine, methionine, and arginine amino acids in the two hypertensive subgroups compared to control group. Moreover, there was a marked decrease of vitamin D level in hypertensive population in comparison with control.&#x0D; Conclusion: There is obvious association between PFAAs profile changes, hypovitaminosis D and hypertension.

Use of plasma-free amino acids as biomarkers for detecting and predicting disease risk.

This paper reviews developments regarding the use of plasma-free amino acid (PFAA) profiles as biomarkers for detecting and predicting disease risk. This work was initiated and first published in 2006 and was subsequently developed by Ajinomoto Co., Inc. After commercialization in 2011, PFAA-based tests were adopted in over 1500 clinics and hospitals in Japan, and numerous clinician-led studies have been performed to validate these tests. Evidence is accumulating that PFAA profiles can be used for diabetes prediction and evaluation of frailty; in particular, decreased plasma essential amino acids could contribute to the pathophysiology of severe frailty. Integration of PFAA evaluation as a biomarker and effective essential amino acid supplementation, which improves physical and mental functions in the elderly, could facilitate the development of precision nutrition, including personalized solutions. This present review provides the background for the technology as well as more recent clinical findings, and offers future possibilities regarding the implementation of precision nutrition.

The free amino acid profiles and metabolic biomarkers of predicting the chemotherapeutic response in advanced sarcoma patients

Metabolomics is an emerging field in cancer research. Plasma free amino acid profiles (PFAAs) have shown different features in various cancers, but the characteristic in advanced sarcoma remains unclear. We aimed to uncover the specific PFAAs in advanced sarcoma and to find the relationship between the altering of PFAAs and response to chemotherapy. We analyzed the differences in PFAAs between 23 sarcoma patients and 30 healthy subjects basing on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Then, we compared the dynamics of PFAAs after chemotherapy between improvement group and deterioration group. We identified seven biological differential amino acids and four pathways which were perturbed in the sarcoma patients compared with healthy subjects. After one cycle chemotherapy, the levels of γ-aminobutyric acid (GABA) and carnosine (Car) decreased significantly in the improvement group but not in deterioration group. The levels of α-aminobutyric acid (Abu) increased significantly in the deterioration group but not in the improvement group. Our study suggests the potential specific PFAAs in sarcoma patients. The unusual amino acids and metabolic pathways may provide ideas for clinical drugs targeting therapy. Three amino acids including Car, GABA and Abu may be metabolic biomarkers playing a role in dynamic monitoring of the therapeutic effect.

Screening Strategy of Pancreatic Cancer in Patients with Diabetes Mellitus

The incidence of pancreatic cancer (PCa) is increasing worldwide and has become one of the leading causes of cancer-related death. Screening for high risk populations is fundamental to overcome this intractable malignancy. Diabetes mellitus (DM) is classically known as a risk factor for PCa. Recently the reverse causality is in the spotlight, that is to say, DM is considered to be a manifestation of PCa. Numbers of epidemiological studies clarified that new-onset DM (≤2-year duration) was predominant in PCa patients and the relative risk for PCa inversely correlated with duration of DM. Among patients with new-onset DM, elder onset, weight loss, and rapid exacerbation of glycemic control were reported to be promising risk factors and signs, and the model was developed by combining these factors. Several pilot studies disclosed the possible utility of biomarkers to discriminate PCa-associated DM from type 2 DM. However, there is no reliable biomarkers to be used in the practice. We previously reported the application of a multivariate index for PCa based on the profile of plasma free amino acids (PFAAs) among diabetic patients. We are further investigating on the PFAA profile of PCa-associated DM, and it can be useful for developing the novel biomarker in the near future.

Moderate intake of BCAA-rich protein improves glucose homeostasis in high-fat-fed mice

Notwithstanding the fact that dietary branched-chain amino acids (BCAAs) have been considered to be a cause of insulin resistance (IR), evidence indicates that BCAA-rich whey proteins (WPs) do not lead to IR in animals consuming high-fat (HF) diets and may instead improve glucose homeostasis. To address the role of BCAA-rich WP as dietary protein in IR and inflammatory response, we fed C57BL/6J mice either high-fat (HF) or low-fat (LF) diets formulated with moderate protein levels (13% w/w) of either WP or hydrolyzed WP (WPH) and compared them with casein (CAS) as a reference. The muscle and plasma free amino acid profiles, inflammatory parameters and glycemic homeostasis were examined. While the LF/CAS diet promoted the rise in triglycerides and inflammatory parameters, the HF/CAS induced typical IR responses and impaired biochemical parameters. No differences in plasma BCAAs were detected, but the HF/WPH diet led to a twofold increase in gastrocnemius muscle free amino acids, including BCAAs. In general, ingestion of WPH was effective at averting or attenuating the damage caused by both the LF and HF diets. No high concentrations of BCAAs in the plasma or signs of IR were found in those mice fed an HF diet along with the hydrolyzed whey proteins. It is concluded that consumption of BCAA-rich whey proteins, especially WPH, does not result in the development of IR.

Role of Plasma Amino Acids Profiles in Pathogenesis and Prediction of Severity in Patients with Drug Resistant Epilepsy

Background: Abnormal plasma levels of free amino acids may predict the severity in patients with drug resistant epilepsy (PRE), having probability to affect their therapeutic approach. Objectives:We aimed to illuminate the effect of plasma free amino acids (PFAAs) profiles on the etiology of patients with PRE and their contribution on the frequencies of epileptic fits. Patients and Methods:We collected clinical and metabolomic data of 90 subjects; 45 of them were PRE patients, and other 45 age and sex matched healthy controls. Quantitative measurements of PFAAs profiles using SykamAutomatic Amino Acid Analyzer S433, in addition to fasting blood sugar, liver function tests, kidney function tests and lipid profile also, were determined. Results: The plasma levels of glutamate, glycine and Gamma amino butyric acid(GABA) plasma levels were significantly increased in PRE group compared to controls (p˂0.0001),their plasma levels also showed significant increase with increased frequency of epileptic fits. Plasma leucine, phenylalanine, aspartate ,ornithine, citrulline, serine and alanine levels (p˂0.0001) were significantly increased in PRE group in relation to healthy controls. Interestingly, on the other hand, histidine, isoleucine, lysine, threonine and the amino acid derivative taurine levels were significantly decreased in PRE patients compared to healthy controls. Conclusion:Few biomarkers of PRE are available to find the severity and rate of progressionof PRE. The present study showed that altered plasma amino acids and their derivatives may be candidate markers for PRE, help explaining its pathogenesis, and for further researches concerning normalization of the disturbed amino acid/s or its derivative/s (GABA and taurine) in managing PRE patients.

Alteration of plasma free amino acids’ level in oral squamous cell carcinoma patients using High Performance Liquid Chromatography

ObjectivesOral cancer inflicts a substantial challenge worldwide being a highly lethal and disfiguring disease. Delayed diagnosis keeps the mortality high. Plasma free amino acids (PFAAs) circulate throughout the body, participating in metabolism. Subsequently, changes in PFAA profile might mirror cancer induced protein metabolism. In this context, this study aims to quantify, compare and correlate PFAAs level in OSCC and control group using High performance liquid chromatography (HPLC). MethodsA total of 60 samples: 30 OSCC subjects and 30 age, sex matched healthy controls were taken. Following clinical examination and histopathological confirmation, 5 ml blood was collected in a tube containing EDTA and centrifuged. The PFAAs levels were quantified using HPLC. ResultsOut of 19 PFAAs, concentration of aspartate, glutamate and arginine were significantly decreased and of asparagine, glutamine and cysteine were significantly increased in OSCC group. Furthermore, comparing well (group I) and moderately (group II) differentiated OSCC group, the level of asparagine was significantly decreased, and of serine significantly increased in group II. Significant alterations were also observed, when group I and II were compared to control group in the following: aspartate, glutamate, asparagine, serine, arginine and cysteine. On comparing stage III, IV OSCC group to control group the levels of aspartate, glutamate, asparagine and cysteine showed significant alterations. ConclusionAltered protein metabolism, as shown in PFAA profile may be employed as a supplementary tool for diagnosing OSCC. Meticulous study of amino acid assays may facilitate in understanding the route of metabolic derangement in OSCC patients.

Associations among amino acid, lipid, and glucose metabolic profiles in childhood obesity

BackgroundPlasma-free amino acid profiles have been reported to correlate with obesity and glucose metabolism, and have been studied as potentially useful biomarkers of lifestyle-related diseases affecting metabolism in adulthood. However, knowledge of these relationships is lacking in children, despite the growing public health problem posed by childhood obesity.The aim of this study was to assess whether plasma-free amino acid profiles can serve as useful biomarkers of lifestyle-related diseases in children with obesity.MethodsThis retrospective study used the medical records of 26 patients (15 male, 11 female) aged 9 or 10 years presenting with moderate to severe obesity and hyperlipidemia between April 2015 and March 2017. A degree of obesity of 30% or more was defined as moderate or severe. Amino acid levels were compared between obese children with and without impaired glucose tolerance using a t-test or Mann–Whitney U test. In addition, the influence of factors such as intima media thickness, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, amino acids, and homeostasis model assessment-insulin resistance (HOMA-IR) were analyzed pairwise using Pearson’s correlation or Spearman’s rank correlation.ResultsHOMA-IR was positively correlated with valine, leucine (Leu), isoleucine, phenylalanine, tryptophan, methionine, threonine, lysine, alanine, tyrosine, glutamate (Glu), proline, arginine, ornithine, total free amino acids (all P < 0.01), and aspartate (P = 0.010). Moreover, blood uric acid levels were positively correlated with Leu (P = 0.005) and Glu (P = 0.019), and negatively correlated with serine, glycine, and asparagine (P = 0.007, P = 0.003, and P = 0.013, respectively).ConclusionsAmino acid profile reflects impaired glucose tolerance and hyperuricemia at an early stage of obesity. It is therefore a useful marker to inform early intervention in children with obesity, as in adults.