OPTICALLY ACTIVE AMINO ACIDS WITH HIGHLY BRANCHED SIDE CHAIN (I) SYNTHESIS OF D- AND L- 2-AMINO-5,5-DIMETHYLHEXANOIC ACID AND 2-AMINO-6,6-DIMETHYLHEPTANOIC ACID

The title compounds were prepared by the enzymatic resolution of the corresponding N-acetylated DL-amino acids methyl esters, which were obtained from t-butyl chloride via an 8-step synthesis.

Diagnostic value of methylated branched chain amino acid transaminase 1/IKAROS family zinc finger 1 for colorectal cancer

BACKGROUND The diagnostic value of combined methylated branched chain amino acid transaminase 1(BCAT1)/IKAROS family zinc finger 1(IKZF1)in plasma for colorectal cancer(CRC)has been explored since 2015.Recently,several related studies have published their results and showed its diagnostic efficacy.AIM To analyze the diagnostic value of methylated BCAT1/IKZF1 in plasma for screening and postoperative follow-up of CRC.METHODS The candidate studies were identified by searching the PubMed,Embase,Cochrane Library,CNKI,and Wanfang databases from May 31,2003 to June 1,2023.Sensitivity,specificity,and diagnostic accuracy were calculated by merging ratios or means.RESULTS Twelve eligible studies were included in the analysis,involving 6561 participants.The sensitivity of methylated BCAT1/IKZF1 in plasma for CRC diagnosis was 60%[95%confidence interval(CI)53-67]and specificity was 92%(95%CI:90-94).The positive and negative likelihood ratios were 8.0(95%CI:5.8-11.0)and 0.43(95%CI:0.36-0.52),respectively.Diagnostic odds ratio was 19(95%CI:11-30)and area under the curve was 0.88(95%CI:0.85-0.91).The sensitivity and specificity for CRC screening were 64%(95%CI:59-69)and 92%(95%CI:91-93),respectively.The sensitivity and specificity for recurrence detection during follow-up were 54%CONCLUSION The detection of methylated BCAT1/IKZF1 in plasma,as a non-invasive detection method of circulating tumor DNA,has potential CRC diagnosis,but the clinical application prospect needs to be further explored.

Impairment of innate immune responses in cirrhotic patients and treatment by branched-chain amino acids

It has been reported that host defense responses, such as phagocytic function of neutrophils and natural killer (NK) cell activity of lymphocytes, are impaired in cirrhotic patients. This review will concentrate on the impairment of innate immune responses in decompensated cirrhotic patients and the effect of the treatment by branched-chain amino acids (BCAA) on innate immune responses. We already reported that phagocytic function of neutrophils was significantly improved by 3-mo BCAA supplementation. In addition, the changes of NK activity were also significant at 3 mo of supplementation compared with before supplementation. Also, Fisher’s ratios were reported to be significantly increased at 3 mo of BCAA supplementation compared with those before oral supplementation. Therefore, administration of BCAA could reduce the risk of bacterial and viral infection in patients with decompensated cirrhosis by restoring impaired innate immune responses of the host. In addition, it was also revealed that BCAA oral supplementation could reduce the risk of development of hepatocellular carcinoma in cirrhotic patients. The mechanisms of the effects will also be discussed in this review article.

Synergistic renoprotective effect of a compiled branched-chain amino acids and Cymbopogon schoenanthus extract against experimentally induced oxido-nitrosative renal insult

Objective: To better investigate the protective role of branched-chain amino acids(BCAAs)and Cymbopogon schoenanthus(CS) extract against the potassium dichromate(PDC)-induced oxido-nitrosative nephrotoxic insult in the experimental rat model. Methods: Thirty male rats were randomly divided into five equal groups: The 1 st group served as control; the 2^(nd)was injected with a single dose of PDC(15 mg/kg b.w i.p.);the 3^(rd), 4^(th), and 5^(th) groups were respectively treated with BCAAs, CS, and their combination for 15 d prior to induction of renal insult via PDC single dose(15 mg/kg b.w s.c.). The experimental period was terminated in all groups 2 d after induction of renal insult. The harvested kdney samples were divided for biochemical assays and histological examination. Results: The PDC-induced nephrotoxic effect caused a depletion of renal oxidative scavengers glutathione, superoxide dismutase with consequent lipo-oxidative cellular membrane deterioration manifested by a rise in malonaldehyde, oxidized glutathione, myeloperoxidase and the concomitant increase in inflammatory response elements tumor necrosis factor α, nitric oxide, and interleukin 1 β.Moreover, the comet assay and increased 8-hydroxy-2-deoxyguanosine proved an accelerated apoptotic DNA fragmentation. These local renal changes were met with global altered blood biochemistry. The BCAAs and CS or their compiled administration showed an ameliorative effect against PDC-induced nephrotoxic in a synergistic pattern. Conclusions: Both BCAAs and CS or their combined administration afford potential competitors against renal insult induced by polyvalent anion pollutants in experimentally studied animals model. As a route for novel drug discovery, further investigation should be attempted to optimize their augmenting reno-protecting potential.

Effect of branched-chain amino acids in patients receiving intervention for hepatocellular carcinoma

AIM: To investigate the usefulness of branched-chain amino acids (BCAA) before transarterial chemoembolization (TACE) or radiofrequency ablation (RFA).

Herbicide-Resistant Mutations in Acetolactate Synthase Can Reduce Feedback Inhibition and Lead to Accumulation of Branched-Chain Amino Acids

The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are essential amino acids that are critical for animal growth and development. Animals need to obtain BCAAs from their diet because they cannot synthesize them. Plants are the ultimate source of these amino acids. Acetolactate synthase (ALS) is the first common enzyme in the biosynthesis of BCAAs. The metabolic control of BCAA biosynthesis involves allosteric regulation of ALS by the end-products of the pathway, i.e., valine, leucine and isoleucine. ALS holoenzyme seems to consist of two large catalytic subunits and two small regulatory subunits. In a previous study, using homologous recombination dependent gene targeting we created rice plants in which W548Land S627I mutations were induced into the endogenous gene encoding the ALS catalytic subunit. These two amino acid substitutions conferred hypertolerance to the ALS-inhibiting herbicide bispyripac-sodium. In this study, we revealed that feedback regulation by valine and leucine was reduced by these two amino acid substitutions. Furthermore, in leaves and seeds of ALS mutants with W548Land/or S627I substitution, a 2- to 3-fold increase in BCAAs was detected. Our results suggest that the ALS catalytic subunit is also involved in feedback regulation of ALS, and that judicious modification of the regulatory and catalytic subunits of ALS-coding genes by gene targeting can lead to the efficient accumulation of BCAA in plants.

Functional microbiomics reveals branched-chain amino acids depletion for alleviation of insulin resistance by berberine

Increased circulating branched-chain amino acids(BCAAs)have been involved in the pathogenesis of obesity and insulin resistance.However,evidence relating berberine(BBR),gut microbiota,BCAAs,and insulin resis⁃tance is limited.Here,we showed that BBR could effectively rectify steatohepatitis and glucose intolerance in high-fat diet(HFD)-fed mice.BBR reorganized gut microbiota populations under both the normal chow diet(NCD)and HFD.Particu⁃larly,BBR noticeably decreased the relative abundance of BCAA-producing bacteria,including order Clostridiales;fami⁃lies Streptococcaceae,Clostridiaceae,and Prevotellaceae;and genera Streptococcus and Prevotella.Compared with the HFD group,predictive metagenomics indicated a reduction in the proportion of gut microbiota genes involved in BCAA biosynthesis but the enrichment genes for BCAA degradation and transport by BBR treatment.Accordingly,the elevated serum BCAAs of HFD group were significantly decreased by BBR.Furthermore,the Western blotting results implied that BBR could promote the BCAA catabolism in the liver and epididymal white adipose tissues of HFD-fed mice by acti⁃vation of the multienzyme branched-chain α-ketoacid dehydrogenase complex,whereas by inhibition of the phosphoryla⁃tion state of BCKDHA(E1α subunit)and branched-chain α-ketoacid dehydrogenase kinase.The ex vivo assay further confirmed that BBR could increase BCAA catabolism in both AML12 hepatocytes and 3T3-L1 adipocytes.Finally,data from healthy subjects and diabetics confirmed that BBR could improve glycemic control and modulate circulating BCAAs.Besides,functional microbiomics integrated high-throughput microbial genomics,metabolomics and molecular biotechnology has also been successfully applied to reveal the anti-obesity mechanism of hydroxysafflor yellow A.

Branched-chain amino acids in liver diseases

Branched chain amino acids(BCAAs)have been shown to affect gene expression,protein metabolism,apoptosis and regeneration of hepatocytes,and insulin resistance.They have also been shown to inhibit the proliferation of liver cancer cells in vitro,and are essential for lymphocyte proliferation and dendritic cell maturation.In patients with advanced chronic liver disease,BCAA concentrations are low,whereas the concentrations of aromatic amino acids such as phenylalanine and tyrosine are high,conditions that may be closely associated with hepatic encephalopathy and the prognosis of these patients.Based on these basic observations,patients with advanced chronic liver disease have been treated clinically with BCAA-rich medicines,with positive effects.

A Method to Predict Amino Acids at Proximity of Beta-Sheet Axes from Protein Sequences

A general and elementary protein folding step was described in a previous article. Energy conservation during this folding step yielded an equation with remarkable solutions over the field of rational numbers. Sets of sequences optimized for folding were derived. In this work, a geometrical analysis of protein beta-sheet backbone structures allows the definition of positions of topological interest. They correspond to amino acids’ alpha carbons located on a unique axis crossing all beta-sheet’s strands or at proximity of this axis defined here. These positions of topological interest are shown to be highly correlated with the absence of sequences optimized for folding. Applications in protein structure prediction for the quality assessment of structural models are envisioned.

Plasma Levels of Amino Acids in Japanese Men and Their Changes after the Administration of Glucose and Sucrose

Background: It is not known whether plasma amino acids levels are different between young and old men in Japan. No research has been reported about changes in plasma levels of amino acids after the administration of glucose or sucrose to young and aged men. Objective: We want to know whether there are age differences in plasma levels of amino acids and if the administration of glucose or sucrose influences their levels. Results: Old people had lower plasma levels of most of amino acids, especially essential and branched-chain amino acids than young men. Plasma levels of amino acids were measured after the administration of 50 grams of glucose or sucrose to young (18 - 22 years old) and aged (≥50 years old) male adults. Plasma levels of total amino acids decreased after the administration of glucose. Decrease in the total amino acid levels was significant in aged men after the administration of sucrose. A significant decrease in plasma levels of total non-essential amino acids was observed at 120 min after the administration of glucose but not sucrose in both aged and young men. Both glucose and sucrose administrations resulted in a significant decrease in the plasma levels of the total essential amino acid levels and branched amino acids in young and aged men. Conclusion: These results suggest that there are age differences in plasma levels of amino acids. Upon the administration of glucose or sucrose amino acids, particularly essential amino acids, decreased in plasma. These amino acids may be transported from the blood soon after the administration of sugar (glucose or sucrose) to the tissues, such as muscles, possibly due to an increase in the insulin levels.

支链氨基酸有效预测慢性阻塞性肺病的急性加重

目的:探讨支链氨基酸(BCAAs)代谢在慢性阻塞性肺病(COPD)发生机制中的作用。方法:收集42例COPD稳定期患者纳入COPD组,40例COPD急性加重(AECOPD)期患者纳入AECOPD组,收集同期46例健康体检者为对照组,采集外周血,应用液相色谱-质谱分析检测BCAAs水平,酶联免疫吸附(ELISA)法检测炎症因子水平,并对二者的相关性进行分析。结果:与对照组比较,COPD组及AECOPD组患者血浆亮氨酸、缬氨酸水平更低,且AECOPD组低于COPD组;血浆白介素(IL)-8、C-反应蛋白(CRP)水平更高,且AECOPD组高于COPD组(P均<0.001)。血浆中亮氨酸、缬氨酸水平与IL-8、CRP水平呈负相关(r=-0.64、-0.71、-0.73、-0.73,P均<0.05)。结论:BCAAs代谢可能通过炎症反应参与COPD的发生,临床中BCAAs水平有可能成为检测COPD急性加重潜在的生物标志物。

支链氨基酸代谢物对风湿性心脏瓣膜病体外循环术后低心排血量的预测价值

目的:探讨支链氨基酸代谢物对风湿性心脏瓣膜病病人行体外循环术后发生低心排血量事件的预测价值。方法:选取2019年1月—2022年1月我院收治的风湿性心脏瓣膜病病人154例作为研究对象,根据体外循环术后是否出现低心排血量,将病人分为低心排血量组(52例)和非低心排血量组(102例)。对比分析两组病人情况,多因素Logistic回归分析低心排血量事件的影响因素。Cox比例风险模型调整混杂变量,分析支链氨基酸代谢物和传统标志物与低心排血量事件的关联性。GRACE风险评分探讨支链氨基酸和传统标志物结合后对低心排血量的预测能力。Cox回归评价支链氨基酸代谢物和传统标志物之间的交互作用。建立回归方程y=1-1/(1+e-z)预测模型并进行验证。结果:脑钠肽、肌钙蛋白I、亮氨酸、缬氨酸、异亮氨酸等是低心排血量事件的独立危险因素。随着脑钠肽、肌钙蛋白I、亮氨酸、缬氨酸、异亮氨酸水平的升高,与低心排血量事件的关联效应也更强。支链氨基酸代谢物和传统标志物结合,会提高GRACE风险评分对低心排血量的预测能力。异亮氨酸联合脑钠肽前体对低心排血量事件的预测效应最高。经Bootstrap自抽样,预测模型区分度、准确度较好。结论:支链氨基酸代谢物和低心排血量密切相关。支链氨基酸代谢物加入传统标志物中,会提高对低心排血量的预测能力,有助于改善风湿性心脏瓣膜病病人预后。

微生物组及其代谢物调控神经胶质瘤的研究进展

神经胶质瘤是最常见的脑肿瘤,占恶性脑肿瘤的80%,其中多形性胶质母细胞瘤是最具侵袭性的神经胶质瘤类型,是全球难治性肿瘤之一。目前胶质母细胞瘤的主要治疗手段是手术,而手术不良反应大,易复发,且生存率不高。因此寻求更多潜在生物标志物,提高生存率仍是神经胶质瘤研究的重要挑战。越来越多的证据表明,瘤内微生物组及肠道微生物组对神经胶质瘤的进展和治疗有重要影响,且特定微生物群与肿瘤进展的不同阶段有关。与此同时,微生物代谢物与中枢神经系统之间的相互作用及机制受到广泛关注。然而,微生物组、代谢物与神经胶质瘤之间的相关性仍不明确。本文综述了目前与神经胶质瘤相关微生物组的研究进展,重点介绍了瘤内微生物组、肠道微生物组及其代谢物,如氨基酸(包括色氨酸、精氨酸、谷氨酸)、短链脂肪酸、神经递质类物质等,与神经胶质瘤之间的关系。并简要概述了益生菌对神经胶质瘤的改善作用。本综述为基于微生物组提早预测及治疗神经胶质瘤提供相关依据。

支链氨基酸代谢与2型糖尿病关系的研究进展

支链氨基酸(BCAAs)是一类因存在脂肪烃链而得名的必需氨基酸,包括亮氨酸、异亮氨酸以及缬氨酸。BCAAs同胰岛素抵抗的关系于1964年被提出,该类氨基酸在膳食中常见,其循环水平通过对糖脂代谢和胰岛素分泌的调控对2型糖尿病(T2DM)病程发展起着重要的作用。作为一种发病率高、并发症严重的慢性代谢性疾病,糖尿病已经对全球人民生活生产造成了极大的困扰。其中T2DM作为糖尿病中占比最高的类型,正大幅度降低患者的生活质量。本文通过糖脂代谢以及其他相关机制,将BCAAs代谢分解过程与T2DM发生发展联系起来,从而为临床T2DM的治疗诊断提供更多思路。

支链氨基酸的生理功能及其在反刍动物生产中的应用研究进展

支链氨基酸是维持动物机体生长发育、生命活动和生理功能的必需氨基酸。支链氨基酸由于其特殊的分子结构而具有特殊生理功能。近年来研究发现,支链氨基酸具有氧化供能、调节蛋白质代谢、调节脂肪代谢、调节激素分泌、调节免疫、缓解氧化应激等多种功能。本文综述了支链氨基酸的生理功能及其在反刍动物生产中的应用,旨在为支链氨基酸在反刍动物生产中的合理应用提供理论依据和参考。

母马补喂支链氨基酸对哺乳马驹生长性能和粪便菌群的影响

[目的]本试验旨在探究泌乳期伊犁马母马补喂不同剂量的支链氨基酸(BCAAs)对哺乳期马驹生长性能和粪便菌群的影响,为保障马驹哺乳期生长及健康提供参考依据。[方法]选择泌乳期母马及其马驹各20匹(哺乳期马驹在2~3月龄之间,初始体重为97.60 kg±13.24 kg;泌乳期母马体重为392.90 kg±12.18 kg),随机分成4组,每组母马及其马驹各5匹,分别为对照组和试验Ⅰ组、Ⅱ组、Ⅲ组,在相同饲养管理条件下饲养67 d(预饲期7 d,试验期60 d)。试验期间,对照组与试验组母马每天补喂精料补充料2 kg,试验Ⅰ、Ⅱ、Ⅲ组母马分别额外补喂38、76、114 g/d BCAAs。试验前1 d和第60天测量马驹的体尺和体重数据,第60天采用直肠取粪法采集马驹粪便,分析马驹粪便菌群多样性。[结果]试验第60天,试验Ⅲ组马驹的胸围和体重显著高于对照组(P<0.05),试验Ⅱ组马驹的体重显著高于对照组(P<0.05);试验Ⅰ、Ⅱ、Ⅲ组和对照组粪便菌群OTUs数量分别为4553、4483、4607和3839。各组间Alpha多样性指数以及观测到的物种数均无显著差异(P>0.05)。试验Ⅱ组马驹粪便螺旋体菌门相对丰度显著高于对照组和试验Ⅰ组(P<0.05),毛螺旋菌科相对丰度显著高于对照组和试验Ⅲ组(P<0.05);试验Ⅰ和Ⅱ组的瘤胃球菌科相对丰度均显著高于对照组(P<0.05),试验Ⅲ组的理研菌科相对丰度显著高于对照组(P<0.05)。在属水平上,试验Ⅱ组密螺旋体属的相对丰度最高且显著高于试验Ⅰ组(P<0.05),且瘤胃球菌属相对丰度显著高于其他3个组(P<0.05);试验Ⅲ组普氏菌科未分类菌004相对丰度极显著高于对照组和试验Ⅰ组(P<0.01)。LEfSe分析与PICRUSt2功能预测所表现的差异项目均与肠道发酵代谢、短链脂肪酸的生产、氨基酸的代谢相关。[结论]给伊犁马母马补喂不同剂量的BCAAs可促进哺乳马驹胸围和体重的增长,提高其肠道有益菌群的丰度,降低有害菌群的丰度,以母马补喂76 g/d BCAAs效果最佳。

支链氨基酸转氨酶1在食管鳞癌中的表达及其临床意义

目的探讨食管鳞癌(ESCC)患者癌组织中支链氨基酸转氨酶1(BCAT1)的表达及临床意义。方法采用qRT-PCR和Western blot技术检测食管鳞癌细胞系中BCAT1基因的表达水平,筛选出合适的食管癌细胞,作为后续研究。敲低和过表达BCAT1,采用Western blot检测ESCC细胞中BCAT1的蛋白表达水平。CCK-8活力测定、克隆形成实验、划痕实验、Transwell检测ESCC细胞增殖、迁移和侵袭等细胞表型的变化。结果qRT-PCR和Western blot结果显示,与正常细胞相比,BCAT1在ESCC中的相对表达量降低,尤其是KYSE150和Eca109细胞更为明显,因此选择这两株细胞进行研究。CCK-8细胞增殖实验结果显示,细胞在转染BCAT1 siRNA 48 h后,其增殖率明显高于对照组;而过表达BCAT1之后,效果则相反。克隆形成实验结果表明,BCAT1的敲低显著促进ESCC细胞的克隆形成,而BCAT1的过表达显著抑制ESCC细胞的克隆形成。细胞划痕实验和Transwell实验结果表明,与Control siRNA组相比,BCAT1 siRNA组ESCC细胞的迁移和侵袭明显升高;而过表达组中ESCC细胞的迁移和侵袭明显受到抑制。结论BCAT1在ESCC中低表达,BCAT1低表达显著促进ESCC细胞增殖、迁移和侵袭。

家禽支链氨基酸营养需要研究进展

支链氨基酸(branched-chain amino acids,BCAA)在家禽生长、生产性能、免疫功能和肠道健康等方面发挥着重要作用,涉及器官发育、免疫反应、肌肉蛋白周转和基因调控等关键过程。然而,单一BCAA的过量、缺乏或比例失衡均会影响家禽蛋白质合成和肠道健康,因此保持BCAA比例的平衡对于家禽的生产性能至关重要。尽管NRC(1994)提供了肉鸡、蛋鸡和种鸡的BCAA推荐量,但不同日粮蛋白质水平以及不同品种和生长阶段的家禽对BCAA的需求存在差异。同时,鉴于抗生素生长促进剂的禁用及养殖端所面临的多种疾病的挑战,也需要重新评估家禽对BCAA的推荐摄取水平。另外,BCAA在维持肠道完整性、调控肠道微生物组成以及提高机体蛋白周转效率的作用机理研究仍有待进一步探究。本综述在阐述BCAA在家禽中的营养生理作用以及其对生产和健康的基础上,推荐了不同饲养条件下不同肉鸡品种(肉鸡、蛋鸡和种鸡)BCAA需要量,以期为家禽低蛋白日粮BCAA推荐量提供理论参考。

同位素稀释-气相色谱-质谱法测定血清中三种支链氨基酸

建立了一种同位素稀释-气相色谱-质谱法测定血清中三种支链氨基酸含量的检测方法。采用该方法对血清中缬氨酸、亮氨酸、异亮氨酸进行定量分析,结果的相对标准偏差为0.19%~0.46%,平均回收率为99.9%~102.2%。方法重复性好、准确度高、结果准确可靠,可满足临床血清样品中三种氨基酸含量的准确检测。

肿瘤恶液质患者的营养治疗专家共识

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