scholarly journals Structural Rearrangements of a Dodecameric Ketol-Acid Reductoisomerase Isolated from a Marine Thermophilic Methanogen

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1679
Author(s):  
Olivier Nicolas Lemaire ◽  
Marie-Caroline Müller ◽  
Jörg Kahnt ◽  
Tristan Wagner
Keyword(s):  
Amino Acids ◽  
Active Site ◽  
Methanogenic Archaea ◽  
Branched Chain Amino Acids ◽  
Structural Rearrangements ◽  
Coenzyme Binding ◽  
High Conservation ◽  
Branched Chain ◽  
Very High

Ketol-acid reductoisomerase (KARI) orchestrates the biosynthesis of branched-chain amino acids, an elementary reaction in prototrophic organisms as well as a valuable process in biotechnology. Bacterial KARIs belonging to class I organise as dimers or dodecamers and were intensively studied to understand their remarkable specificity towards NADH or NADPH, but also to develop antibiotics. Here, we present the first structural study on a KARI natively isolated from a methanogenic archaea. The dodecameric structure of 0.44-MDa was obtained in two different conformations, an open and close state refined to a resolution of 2.2-Å and 2.1-Å, respectively. These structures illustrate the conformational movement required for substrate and coenzyme binding. While the close state presents the complete NADP bound in front of a partially occupied Mg2+-site, the Mg2+-free open state contains a tartrate at the nicotinamide location and a bound NADP with the adenine-nicotinamide protruding out of the active site. Structural comparisons show a very high conservation of the active site environment and detailed analyses point towards few specific residues required for the dodecamerisation. These residues are not conserved in other dodecameric KARIs that stabilise their trimeric interface differently, suggesting that dodecamerisation, the cellular role of which is still unknown, might have occurred several times in the evolution of KARIs.

scholarly journals Plasma Branched-Chain Amino Acids and Incident Cardiovascular Disease in the PREDIMED Trial

2016 ◽  
Vol 62 (4) ◽  
pp. 582-592 ◽  
Author(s):  
Miguel Ruiz-Canela ◽  
Estefania Toledo ◽  
Clary B Clish ◽  
Adela Hruby ◽  
Liming Liang ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Amino Acids ◽  
Cardiovascular Death ◽  
Branched Chain Amino Acids ◽  
Control Group ◽  
Cvd Risk ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Branched Chain

Abstract BACKGROUND The role of branched-chain amino acids (BCAAs) in cardiovascular disease (CVD) remains poorly understood. We hypothesized that baseline BCAA concentrations predict future risk of CVD and that a Mediterranean diet (MedDiet) intervention may counteract this effect. METHODS We developed a case-cohort study within the Prevención con Dieta Mediterránea (PREDIMED), with 226 incident CVD cases and 744 noncases. We used LC-MS/MS to measure plasma BCAAs (leucine, isoleucine, and valine), both at baseline and after 1 year of follow-up. The primary outcome was a composite of incident stroke, myocardial infarction, or cardiovascular death. RESULTS After adjustment for potential confounders, baseline leucine and isoleucine concentrations were associated with higher CVD risk: the hazard ratios (HRs) for the highest vs lowest quartile were 1.70 (95% CI, 1.05–2.76) and 2.09 (1.27–3.44), respectively. Stronger associations were found for stroke. For both CVD and stroke, we found higher HRs across successive quartiles of BCAAs in the control group than in the MedDiet groups. With stroke as the outcome, a significant interaction (P = 0.009) between baseline BCAA score and intervention with MedDiet was observed. No significant effect of the intervention on 1-year changes in BCAAs or any association between 1-year changes in BCAAs and CVD were observed. CONCLUSIONS Higher concentrations of baseline BCAAs were associated with increased risk of CVD, especially stroke, in a high cardiovascular risk population. A Mediterranean-style diet had a negligible effect on 1-year changes in BCAAs, but it may counteract the harmful effects of BCAAs on stroke.

scholarly journals From mitochondria to healthy aging: The role of branched-chain amino acids treatment: MATeR a randomized study

2020 ◽  
Vol 39 (7) ◽  
pp. 2080-2091 ◽  
Author(s):  
Ilaria Buondonno ◽  
Francesca Sassi ◽  
Giulia Carignano ◽  
Francesca Dutto ◽  
Cinzia Ferreri ◽  
...  
Keyword(s):  
Amino Acids ◽  
Healthy Aging ◽  
Randomized Study ◽  
Branched Chain Amino Acids ◽  
Branched Chain

Amino acid transportation, sensing and signal transduction in the mammary gland: key molecular signalling pathways in the regulation of milk synthesis

2020 ◽  
Vol 33 (2) ◽  
pp. 287-297
Author(s):  
Zhihui Wu ◽  
Jinghui Heng ◽  
Min Tian ◽  
Hanqing Song ◽  
Fang Chen ◽  
...  
Keyword(s):  
Amino Acids ◽  
Mammary Gland ◽  
Milk Protein ◽  
Building Blocks ◽  
Branched Chain Amino Acids ◽  
Signalling Pathways ◽  
Recent Advances ◽  
Branched Chain ◽  
Molecular Signalling Pathways

AbstractThe mammary gland, a unique exocrine organ, is responsible for milk synthesis in mammals. Neonatal growth and health are predominantly determined by quality and quantity of milk production. Amino acids are crucial maternal nutrients that are the building blocks for milk protein and are potential energy sources for neonates. Recent advances made regarding the mammary gland further demonstrate that some functional amino acids also regulate milk protein and fat synthesis through distinct intracellular and extracellular pathways. In the present study, we discuss recent advances in the role of amino acids (especially branched-chain amino acids, methionine, arginine and lysine) in the regulation of milk synthesis. The present review also addresses the crucial questions of how amino acids are transported, sensed and transduced in the mammary gland.

scholarly journals The Role of Skeletal Muscle in The Pathogenesis of Altered Concentrations of Branched-Chain Amino Acids (Valine, Leucine, and Isoleucine) in Liver Cirrhosis, Diabetes, and Other Diseases

2021 ◽  
pp. 293-305
Author(s):  
M Holeček
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Liver Cirrhosis ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Branched Chain Amino Acids ◽  
Acid Oxidation ◽  
Amino Group ◽  
Branched Chain

The article shows that skeletal muscle plays a dominant role in the catabolism of branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) and the pathogenesis of their decreased concentrations in liver cirrhosis, increased concentrations in diabetes, and nonspecific alterations in disorders with signs of systemic inflammatory response syndrome (SIRS), such as burn injury and sepsis. The main role of skeletal muscle in BCAA catabolism is due to its mass and high activity of BCAA aminotransferase, which is absent in the liver. Decreased BCAA levels in liver cirrhosis are due to increased use of the BCAA as a donor of amino group to α-ketoglutarate for synthesis of glutamate, which in muscles acts as a substrate for ammonia detoxification to glutamine. Increased BCAA levels in diabetes are due to alterations in glycolysis, citric acid cycle, and fatty acid oxidation. Decreased glycolysis and citric cycle activity impair BCAA transamination to branched-chain keto acids (BCKAs) due to decreased supply of amino group acceptors (α-ketoglutarate, pyruvate, and oxaloacetate); increased fatty acid oxidation inhibits flux of BCKA through BCKA dehydrogenase due to increased supply of NADH and acyl-CoAs. Alterations in BCAA levels in disorders with SIRS are inconsistent due to contradictory effects of SIRS on muscles. Specifically, increased proteolysis and insulin resistance tend to increase BCAA levels, whereas activation of BCKA dehydrogenase and glutamine synthesis tend to decrease BCAA levels. The studies are needed to elucidate the role of alterations in BCAA metabolism and the effects of BCAA supplementation on the outcomes of specific diseases.

Role of Leucine in Protein Metabolism During Exercise and Recovery

2002 ◽  
Vol 27 (6) ◽  
pp. 646-662 ◽  
Author(s):  
Donald K. Layman
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Branched Chain Amino Acids ◽  
New Findings ◽  
Branched Chain

Exercise produces changes in protein and amino acid metabolism. These changes include degradation of the branched-chain amino acids, production of alanine and glutamine, and changes in protein turnover. One of the amino acid most affected by exercise is the branched-chain amino acid leucine. Recently, there has been an increased understanding of the role of leucine in metabolic regulations and remarkable new findings about the role of leucine in intracellular signaling. Leucine appears to exert a synergistic role with insulin as a regulatory factor in the insulin/phosphatidylinositol-3 kinase (PI3-K) signal cascade. Insulin serves to activate the signal pathway, while leucine is essential to enhance or amplify the signal for protein synthesis at the level of peptide initiation. Studies feeding amino acids or leucine soon after exercise suggest that post-exercise consumption of amino acids stimulates recovery of muscle protein synthesis via translation regulations. This review focuses on the unique roles of leucine in amino acid metabolism in skeletal muscle during and after exercise. Key words: branched-chain amino acids, insulin, protein synthesis, skeletal muscle

Branched-chain amino acids, especially of leucine and valine, mediate the protein restricted response in a piglet model

2020 ◽  
Vol 11 (2) ◽  
pp. 1304-1311 ◽  
Author(s):  
Jie Yin ◽  
Jie Ma ◽  
Yuying Li ◽  
Xiaokang Ma ◽  
Jiashun Chen ◽  
...  
Keyword(s):  
Amino Acids ◽  
Branched Chain Amino Acids ◽  
Branched Chain

Branched-chain amino acids (BCAAs) are reduced in various protein restricted models, while the detailed role of BCAAs in protein restricted response is still obscure.

Sign in / Sign up

Export Citation Format

Share Document