支链氨基酸与心血管疾病的研究进展

支链氨基酸是哺乳动物体内的重要营养物质，支链氨基酸代谢稳态对心功能的维持至关重要，同时参与多种疾病的发生发展过程。近年来也有越来越多的研究表明，支链氨基酸的代谢异常和心血管疾病及多种代谢性疾病有着紧密的联系。现对支链氨基酸代谢过程进行概述，就其在心力衰竭、急性心肌梗死、心肌缺血再灌注损伤、心律失常、糖尿病心肌病、高血压等心血管疾病中的研究进展进行综述，并对未来研究方向予以展望。     

异亮氨酸对机体能量代谢的影响

与能量代谢有关的各种代谢性疾病如糖尿病、脂肪肝、心血管疾病等患病率逐年上升, 其发生不仅与糖脂代谢有关, 也与氨基酸代谢有关。其中研究最为广泛的是支链氨基酸, 异亮氨酸是一种重要的支链氨基酸, 其与代谢性疾病的相关性近年来得到越来越多的关注, 本文就异亮氨酸与能量代谢的研究进展进行综述。     

肝硬化患者支链氨基酸的应用进展

氨基酸主要在肝脏代谢,肝硬化患者的蛋白质、糖类、脂肪代谢紊乱,体内氨基酸代谢失衡,继而引起全身多脏器、多系统的功能不全,出现肝性脑病、食管静脉曲张破裂出血、腹水等并发症,导致较高的病死率。总结了肝硬化患者氨基酸代谢特点及支链氨基酸在肝硬化治疗中的应用,指出支链氨基酸制剂在调整肝病患者的血清氨基酸谱,升高支链氨基酸与芳香族氨基酸的比值,预防肝硬化并发症,提高肝硬化患者生活质量方面具有重要作用。     

支链氨基酸对寿命调控作用的研究进展

支链氨基酸对糖脂代谢、蛋白质合成和寿命等具有重要的调节作用。许多研究报道了循环支链氨基酸水平或饮食摄入支链氨基酸与寿命、骨骼肌减少症、肥胖及糖尿病等疾病息息相关。其中,在不同动物模型中支链氨基酸与寿命之间往往存在相反的作用效果。本文综述了支链氨基酸的生物学特征及其在寿命调控中两种相反的作用及机制,以期为支链氨基酸对衰老的干预研究提供崭新的思路及合理的依据。     

肝癌治愈性切除术后长期口服支链氨基酸:一项前瞻性随机研究

近来肝脏外科注意到了接受肝脏治愈性切除的肝癌患者的营养状况。绝大部分的肝癌患者伴有肝硬化,而且必需在营养状况不理想时接受肝切除手术。肝硬化被认为是处于一个过度分解代谢的“蛋白质营养不良”期。而应用支链氨基酸可以纠正这种“营养不良”。研究旨在阐明,对于那些接受肝切除的原发性肝癌患者,长期口服支链氨基酸对于临床症状、实验室指标、癌肿的复发和提高生存率等方面的影响。 方法:在手术后2～3周内,75位患者被随机列为接受口服支链氨基酸,每天100g,共1     

肝硬化时血浆支链氨基酸水平降低的机制

肝硬化时血浆氨基酸改变的特点是芳香族氨基酸(AAA)升高,支链氨基酸(BCAA)降低;这种改变的重要性在于它和肝性脑病有密切的关系.用富含BCAA的氨基酸液治疗肝性脑病的效益已为许多作者证实.因此,阐明血浆BCAA降低的机制和设计更合理的治疗有重要的意义.芳香族氨基酸主要在肝脏内代谢.肝硬化时血浆AAA水平的升高是由于肝清除能力减低之故.但支链氨基酸主要在外周组织内代谢,其降低与肝脏的代谢无关,而由下列多种因素引起.营养不良和饥饿肝病患者常因食欲不振、饮食习惯不良或有其它合并疾病而经常处于"饥饿"状态.长期饥饿使BCAA氧化供能增加,血浆BCAA降     

某些内科疾病中氨基酸代谢紊乱的意义

众所周知,氨基酸在机体的含氮物质代谢以及蛋白质的合成和更新中占重要地位,并参与激素、酶、维生素和其它一些生物活性物质的合成。有些氨基酸如甘氨酸、γ-氨基丁酸和谷氨酸等是神经递质,另一些氨基酸如支链氨基酸具有特殊的生理功用,如参与脂肪酸和蛋白质的合成,作为体内能量的来源和胰岛素释放的调节物。近10年来,许多学者从测定血液游离氨基酸来了解人体的营养代谢状况,研究     

乙型肝炎血清氨基酸谱变化与肝功能相关性研究

肝脏受损伤时,普遍存在着氨基酸代谢的紊乱.肝脏受损的程度不同,血清氨基酸谱发生的改变也不相同,其特征性的改变表现为芳香族氨基酸(AAA,包括苯丙氨酸、酪氨酸)升高,支链氨基酸(BCAA,包括亮氨酸、异亮氨酸、缬氨酸)降低,BCAA/AA比值降低[1].     

支链氨基酸代谢与妊娠期糖尿病的相关性研究

目的通过检测妊娠期糖尿病(GDM)患者的外周血中支链氨基酸的含量,探讨支链氨基酸代谢与机体糖脂代谢的相关关系。方法选择该院2018年1月—2019年1月期间GDM孕妇56例、血糖正常孕妇58名分别作为GDM组及正常对照组。评估两组孕妇外周血的BCAAs含量、糖代谢以及脂质代谢指标的水平差异,及BCAAs含量与糖脂代谢紊乱的相关关系。结果GDM组血清中亮氨酸与异亮氨酸的总量(84.80±14.64)μmol/L、缬氨酸的含量(115.88±18.19)μmol/L均显著高于正常组(74.33±11.92)μmol/L、(105.38±17.61)μmol/L,差异有统计学意义(t=4.179、3.130,P<0.05);GDM组外周血糖代谢指标糖化血红蛋白、空腹胰岛素以及胰岛素抵抗指数的水平均显著高于正常对照组;GDM组外周血中脂质代谢指标总胆固醇、高密度脂蛋白、低密度脂蛋白的含量显著低于正常对照组,甘油三酯的含量显著高于正常对照组,差异有统计学意义(P<0.05)。相关性分析表明,GDM组的支链氨基酸含量与机体糖脂代谢紊乱程度呈正相关。结论GDM组孕妇存在支链氨基酸含量升高的现象,可能是促进机体糖脂代谢紊乱的重要因素。     

支链氨基酸代谢异常在心力衰竭发生发展中作用的研究进展

心肌能量代谢改变在心力衰竭的发生发展中起着重要作用。近年来研究发现,血浆中支链氨基酸(BCAAs)及其代谢产物水平的增高是心力衰竭的重要特征,并形成恶性反馈环,最终导致心力衰竭进展。因此,促进BCAAs分解代谢、减少代谢产物蓄积及恢复BCAAs代谢平衡,有望成为心力衰竭的新治疗靶点。本文对BCAAs代谢异常与心力衰竭的关系进行综述。     

Branched-chain amino acid metabolism in heart disease: an epiphenomenon or a real culprit?

Metabolic remodelling is an integral part of the pathogenesis of heart failure. Although much progress has been made in our current understanding of the metabolic impairment involving carbohydrates and fatty acids in failing hearts, relatively little is known about the changes and potential impact of amino acid metabolism in the onset of heart diseases. Although most amino acid catabolic activities are found in the liver, branched-chain amino acid (BCAA) catabolism requires activity in several non-hepatic tissues, including cardiac muscle, diaphragm, brain and kidney. In this review, the new insights into the regulation of cardiac BCAA catabolism and functional impact on cardiac development and physiology will be discussed along with the potential contribution of impairment in BCAA catabolism to heart diseases. A particular focus will be the new information obtained from recently developed genetic models with BCAA catabolic defects and metabolomic studies in human and animal models. These studies have revealed the potential role of BCAA catabolism in cardiac pathophysiology and have helped to distinguish BCAA metabolic defects as an under-appreciated culprit in cardiac diseases rather than an epiphenomenon associated with metabolic remodelling in the failing heart.     

Blood amine acid levels in patients with insulin excess (functioning insulinoma) and insulin deficiency (diabetic ketosis).

Blood amino acid concentrations were determined in the postabsorptive state in nine patients with insulin excess (functioning insulinomas), nine juvenile-type diabetics with insulin deficiency (diabetic ketosis due to insulin withdrawal), six juvenile diabetics in moderate metabolic control, and five healthy control subjects. Blood branched-chain amino acid (BCAA) levels were elevated in diabetic ketosis and decreased in patients with insulinomas. Blood concentrations of BCAA were significantly correlated to blood glucose levels, and in diabetics they were also correlated to blood ketone bodies, serum free fatty acids, and glycerol levels. These data indicate an inverse relationship between circulating effective insulin levels and blood BCAA concentrations. It is suggested that blood levels of BCAA might represent an indicator of insulin-dependent alterations of protein metabolism.     

Interrupting the mechanisms of brain injury in a model of maple syrup urine disease encephalopathy

Maple syrup urine disease (MSUD) was first recognized as an inherited lethal encephalopathy beginning in the first week of life and associated with an unusual odor in the urine of affected children. It was later confirmed as a deficiency of branched-chain keto acid dehydrogenase (BCKDH), which is the second step in branched-chain amino acid (BCAA) breakdown. MSUD is characterized by BCAA and branched-chain keto acid (BCKA) accumulation. BCAAs are essential amino acids and powerful metabolic signals with severe consequences of both deprivation and accumulation. Treatment requires life-long dietary restriction and monitoring of BCAAs. However, despite excellent compliance, children commonly suffer metabolic decompensation during intercurrent illness resulting in life-threatening cerebral edema and dysmyelination. The mechanisms underlying brain injury have been poorly understood. Recent studies using newly developed mouse models of both classic and intermediate MSUD have yielded insight into the consequences of rapid BCAA accumulation. Additionally, these models have been used to test preliminary treatments aimed at competing with blood-brain barrier transport of BCAA using norleucine. Assessment of biochemical changes with and without treatment suggests different roles for BCAA and BCKA in the mechanism of brain injury.     

The effect of supplementation with branched-chain amino acids in patients with liver cirrhosis

Aim: We investigated the effect of supplementation with branched-chain amino acids (BCAA) in patients with liver cirrhosis on the change of energy metabolism as well as glucose tolerance. Methods: Thirty liver cirrhosis patients underwent nutrient supervision by a dietician for one week. They were then prescribed oral supplementation with three packs of a BCAA nutrient (Livact 4.15 g/pack; Ajinomoto Pharma, Tokyo, Japan), taken three times a day: after breakfast, dinner and before sleep. The change in energy metabolism and glucose tolerance was examined using an indirect calorimeter and 75 g oral glucose tolerance test (75 g OGTT). Results: Non-protein respiratory quotient (npRQ) as well as branched-chain amino acid/tyrosine ratio (BTR) showed significant improvement, especially in patients with a creatinine height index (CHI) greater than 80. There was also a significant correlation between npRQ after one week of BCAA supplementation and the CHI. The patients with CHI greater than 80 and those with borderline pattern assessed by 75 g OGTT showed significant improvement in impaired glucose tolerance. Conclusion: Liver cirrhosis patients with CHI greater than 80 are the first candidates for BCAA supplementation. These patients showed improvement not only in energy metabolism and BTR, but also glucose tolerance.     

Amino acid metabolism during exercise in trained rats: the potential role of carnitine in the metabolic fate of branched-chain amino acids

The influence of endurance training and an acute bout of exercise on plasma concentrations of free amino acids and the intermediates of branched-chain amino acid (BCAA) metabolism were investigated in the rat. Training did not affect the plasma amino acid levels in the resting state. Plasma concentrations of alanine (Ala), aspartic acid (Asp), asparagine (Asn), arginine (Arg), histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), and valine (Val) were significantly lower, whereas glutamate (Glu), glycine (Gly), ornithine (Orn), tryptophan (Trp), tyrosine (Tyr), creatinine, urea, and ammonia levels were unchanged, after one hour of treadmill running in the trained rats. Plasma concentration of glutamine (Glu), the branched-chain keto acids (BCKA) and short-chain acyl carnitines were elevated with exercise. Ratios of plasma BCAA/BCKA were dramatically lowered by exercise in the trained rats. A decrease in plasma-free carnitine levels was also observed. These data suggest that amino acid metabolism is enhanced by exercise even in the trained state. BCAA may only be partially metabolized within muscle and some of their carbon skeletons are released into the circulation in forms of BCKA and short-chain acyl carnitines.     

Maple syrup urine disease mutation spectrum in a cohort of 40 consanguineous patients and insilico analysis of novel mutations

Metabolic Brain Disease - Maple syrup urine disease is the primary aminoacidopathy affecting branched-chain amino acid (BCAA) metabolism. The disease is mainly caused by the deficiency of an enzyme...     

Administration of branched chain amino acids prevents bacterial translocation after liver resection in the cirrhotic rat

After major liver resection, bacterial infectious complications, including sepsis and endotoxemia, can be at least in part, attributed to translocation of enteric bacteria and endotoxin. We evaluated the effectiveness of the enteral and parenteral administration of branched-chain amino acids (BCAA) in preventing bacterial translocation after 70% liver resection in rats with thioacetamide-induced-cirrhosis. Bacterial translocation after hepatectomy was induced by a disturbance of protein metabolism in intestinal epithelial cells. However, the administration of BCAA, particularly via the enteral route, improved amino acid metabolism in the gut and stimulated the synthesis of nonsecreted protein and the proliferation of crypt cells, thereby preventing bacterial translocation after liver resection. Improvement in this cascade of metabolic reactions is believed to have been responsible for the improved outcome after extensive resection of the cirrhotic liver.     

Branched-chain amino acid metabolism in isolated perfused liver of cirrhotic rats.

We examined the possible contribution of the liver to the alterations in branched-chain amino acid (BCAA) metabolism in cirrhosis. The livers of male Sprague-Dawley rats with CCl4-induced cirrhosis were removed and placed in a recirculating perfusion system. Net amino acid uptake and release were determined over 55 min. Results were compared with those obtained with control animals, which were either pair-fed or fed ad libitum. Intrahepatic amino acid concentrations were determined at the end of the perfusion. The release of isoleucine and leucine was significantly lower in the cirrhotic livers than in the controls fed ad libitum. There was no difference between the cirrhotic and pair-fed groups with regard to the fluxes of the three BCAA. Intrahepatic concentrations of BCAA were reduced only in pair-fed controls. These results suggest that both cirrhosis and a low protein/calorie diet alter hepatic BCAA flux, but via different mechanisms. In cirrhosis, alterations could be due both to low food intake and to BCAA metabolism in non-parenchymal cells.     

Branched-Chain Amino Acid Metabolism in Isolated Perfused Liver of Cirrhotic Rats

We examined the possible contribution of the liver to the alterations in branched-chain amino acid (BCAA) metabolism in cirrhosis. The livers of male Sprague-Dawley rats with CCl₄-induced cirrhosis were removed and placed in a recirculating perfusion system. Net amino acid uptake and release were determined over 55 min. Results were compared with those obtained with control animals, which were either pair-fed or fed ad libitum. Intrahepatic amino acid concentrations were determined at the end of the perfusion. The release of isoleucine and leucine was significantly lower in the cirrhotic livers than in the controls fed ad libitum. There was no difference between the cirrhotic and pair-fed groups with regard to the fluxes of the three BCAA. Intrahepatic concentrations of BCAA were reduced only in pair-fed controls. These results suggest that both cirrhosis and a low protein/calorie diet alter hepatic BCAA flux, but via different mechanisms. In cirrhosis, alterations could be due both to low food intake and to BCAA metabolism in non-parenchymal cells.     

Nutritional therapy in cirrhosis

Abstract   In recent years increasing interest has been given to nutritional therapy in a variety of chronic diseases, including cirrhosis. Protein/calorie malnutrition is a common feature of advanced liver disease, and considerably affects prognosis. Hence, the need for nutritional support to provide patients with the minimum protein requirements to balance increased catabolism. Although most patients tolerate normal protein supply, in subjects with impending encephalopathy a nutritional support with branched-chain amino acids (BCAA) was suggested on the basis of neuro-pharmacological studies. A large, randomized trial has recently provided evidence that BCAA may be superior to equicaloric and equinitrogenous supplements, improving survival and retarding hepatocellular failure. Administration schedules including a late evening supplementation may be particularly helpful. Biochemical studies are providing the rationale for the beneficial effects, showing that leucine may be an important regulator of amino acid/protein metabolism.