Whole-body metabolic fate of branched-chain amino acids

2021 ◽  
Vol 478 (4) ◽  
pp. 765-776
Author(s):  
Megan C. Blair ◽  
Michael D. Neinast ◽  
Zoltan Arany
Keyword(s):  
Amino Acids ◽  
Branched Chain Amino Acids ◽  
The Body ◽  
Whole Body ◽  
Key Factors ◽  
Tissue Mass ◽  
Branched Chain ◽  
Ketoacid Dehydrogenase ◽  
Rate Limiting ◽  
Total Tissue

Oxidation of branched-chain amino acids (BCAAs) is tightly regulated in mammals. We review here the distribution and regulation of whole-body BCAA oxidation. Phosphorylation and dephosphorylation of the rate-limiting enzyme, branched-chain α-ketoacid dehydrogenase complex directly regulates BCAA oxidation, and various other indirect mechanisms of regulation also exist. Most tissues throughout the body are capable of BCAA oxidation, and the flux of oxidative BCAA disposal in each tissue is influenced by three key factors: 1. tissue-specific preference for BCAA oxidation relative to other fuels, 2. the overall oxidative activity of mitochondria within a tissue, and 3. total tissue mass. Perturbations in BCAA oxidation have been implicated in many disease contexts, underscoring the importance of BCAA homeostasis in overall health.

Isoleucine Plays an Important Role for Maintaining Immune Function

2019 ◽  
Vol 20 (7) ◽  
pp. 644-651 ◽  
Author(s):  
Changsong Gu ◽  
Xiangbing Mao ◽  
Daiwen Chen ◽  
Bing Yu ◽  
Qing Yang
Keyword(s):  
Amino Acids ◽  
Acid Metabolism ◽  
Branched Chain Amino Acids ◽  
Whole Body ◽  
Immune Functions ◽  
Host Defense Peptides ◽  
Innate And Adaptive Immunity ◽  
Physiological Functions ◽  
Branched Chain ◽  
The Relationship

Branched chain amino acids are the essential nutrients for humans and many animals. As functional amino acids, they play important roles in physiological functions, including immune functions. Isoleucine, as one of the branched chain amino acids, is also critical in physiological functions of the whole body, such as growth, immunity, protein metabolism, fatty acid metabolism and glucose transportation. Isoleucine can improve the immune system, including immune organs, cells and reactive substances. Recent studies have also shown that isoleucine may induce the expression of host defense peptides (i.e., β-defensins) that can regulate host innate and adaptive immunity. In addition, isoleucine administration can restore the effect of some pathogens on the health of humans and animals via increasing the expression of β-defensins. Therefore, the present review will emphatically discuss the effect of isoleucine on immunity while summarizing the relationship between branched chain amino acids and immune functions.

scholarly journals Quantitative Analysis of the Whole-Body Metabolic Fate of Branched-Chain Amino Acids

2019 ◽  
Vol 29 (2) ◽  
pp. 417-429.e4 ◽  
Author(s):  
Michael D. Neinast ◽  
Cholsoon Jang ◽  
Sheng Hui ◽  
Danielle S. Murashige ◽  
Qingwei Chu ◽  
...  
Keyword(s):  
Amino Acids ◽  
Quantitative Analysis ◽  
Branched Chain Amino Acids ◽  
Whole Body ◽  
Metabolic Fate ◽  
Branched Chain

scholarly journals Effects of branched chain amino acids infusion on whole‐body plasma glucose disposal: a pilot study

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Sarah Everman ◽  
Lawrence J Mandarino ◽  
Guilherme M Puga ◽  
Christian Meyer ◽  
Christos S Katsanos
Keyword(s):  
Amino Acids ◽  
Pilot Study ◽  
Plasma Glucose ◽  
Branched Chain Amino Acids ◽  
Whole Body ◽  
Glucose Disposal ◽  
Branched Chain

scholarly journals Metabolic effects of low cortisol during exercise in humans

1998 ◽  
Vol 84 (3) ◽  
pp. 939-947 ◽  
Author(s):  
Pedro Del Corral ◽  
Edward T. Howley ◽  
Mike Hartsell ◽  
Muhammad Ashraf ◽  
Mary Sue Younger
Keyword(s):  
Amino Acids ◽  
Growth Hormone ◽  
Plasma Glucose ◽  
Respiratory Exchange Ratio ◽  
Branched Chain Amino Acids ◽  
Physiological Effect ◽  
Metabolic Effects ◽  
Whole Body ◽  
Branched Chain ◽  
Exercise In Humans

This study examined the physiological effect of reduced plasma cortisol (C) during prolonged exercise in humans. The effects of normal C (NC) were compared with metyrapone-induced low C (LC) on plasma substrate availability and the respiratory exchange ratio during 2 h of exercise at ∼60% peak O2 consumption in nine subjects. The C responses were compared with preexercise (Pre) levels and with a rest day (Con). At rest, C was attenuated by ∼70% for LC compared with NC. At rest, plasma glucose, lactate, glycerol, β-hydroxybutyrate, alanine, branched-chain amino acids, insulin, glucagon, growth hormone, epinephrine, and norepinephrine were similar under LC and NC ( P > 0.05). During exercise under NC, plasma C increased compared with Pre, whereas it remained unchanged during LC. During NC, plasma C was elevated at 90 min (compared with Con) and at 120 min (compared with Con and Pre). During exercise, plasma glucose decreased to the same extent and lactate was similar under both conditions, whereas plasma glycerol, β-hydroxybutyrate, alanine, and branched-chain amino acids were higher ( P < 0.01) under NC. Plasma insulin declined ( P = 0.01) to a greater extent under LC, whereas growth hormone, epinephrine, and norepinephrine tended to be higher (0.05 ≤ P ≤ 0.10). Plasma glucagon increased under both conditions ( P < 0.01). The respiratory exchange ratio did not differ between conditions. We conclude that, during exercise, 1) C accelerates lipolysis, ketogenesis, and proteolysis; 2) under LC, glucoregulatory hormone adjustments maintain glucose homeostasis; and 3) LC does not alter whole body substrate utilization or the ability to complete 2 h of moderate exercise.

scholarly journals Associations between Plasma Branched Chain Amino Acids and Health Biomarkers in Response to Resistance Exercise Training Across Age

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3029
Author(s):  
Mariwan H. Sayda ◽  
Bethan E. Phillips ◽  
John P. Williams ◽  
Paul L. Greenhaff ◽  
Daniel J. Wilkinson ◽  
...  
Keyword(s):  
Amino Acids ◽  
Exercise Training ◽  
Resistance Exercise ◽  
Branched Chain Amino Acids ◽  
Metabolic Health ◽  
Whole Body ◽  
Gas Chromatography Mass Spectrometry ◽  
Resistance Exercise Training ◽  
Fasting Plasma ◽  
Branched Chain

Leucine, isoleucine and valine (i.e., the branched chain amino acids, BCAA) play a key role in the support of tissue protein regulation and can be mobilized as energy substrates during times of starvation. However, positive relationships exist between elevated levels of BCAA and insulin resistance (IR). Thus, we sought to investigate the links between fasting plasma BCAA following a progressive resistance exercise training (RET) programme, an intervention known to improve metabolic health. Fasting plasma BCAA were quantified in adults (young: 18–28 y, n = 8; middle-aged: 45–55 y, n = 9; older: 65–75 y, n = 15; BMI: 23–28 kg/m2, both males and females (~50:50), in a cross-sectional, intervention study. Participants underwent 20-weeks whole-body RET. Measurements of body composition, muscle strength (1-RM) and metabolic health biomarkers (e.g., HOMA-IR) were made at baseline and post-RET. BCAA concentrations were determined by gas-chromatography mass spectrometry (GC-MS). No associations were observed across age with BCAA; however, RET elicited (p < 0.05) increases in plasma BCAA (all age-groups), while HOMA-IR scores reduced (p < 0.05) following RET. After RET, positive correlations in lean body mass (p = 0.007) and strength gains (p = 0.001) with fasting BCAA levels were observed. Elevated BCAA are not a robust marker of ageing nor IR in those with a healthy BMI; rather, despite decreasing IR, RET was associated with increased BCAA.

scholarly journals Branched-chain Amino Acids: Catabolism in Skeletal Muscle and Implications for Muscle and Whole-body Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Gagandeep Mann ◽  
Stephen Mora ◽  
Glory Madu ◽  
Olasunkanmi A. J. Adegoke
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Chronic Diseases ◽  
Branched Chain Amino Acids ◽  
Whole Body ◽  
Management Options ◽  
Impaired Metabolism ◽  
Whole Body Metabolism ◽  
Branched Chain ◽  
The Impact

Branched-chain amino acids (BCAAs) are critical for skeletal muscle and whole-body anabolism and energy homeostasis. They also serve as signaling molecules, for example, being able to activate mammalian/mechanistic target of rapamycin complex 1 (mTORC1). This has implication for macronutrient metabolism. However, elevated circulating levels of BCAAs and of their ketoacids as well as impaired catabolism of these amino acids (AAs) are implicated in the development of insulin resistance and its sequelae, including type 2 diabetes, cardiovascular disease, and of some cancers, although other studies indicate supplements of these AAs may help in the management of some chronic diseases. Here, we first reviewed the catabolism of these AAs especially in skeletal muscle as this tissue contributes the most to whole body disposal of the BCAA. We then reviewed emerging mechanisms of control of enzymes involved in regulating BCAA catabolism. Such mechanisms include regulation of their abundance by microRNA and by post translational modifications such as phosphorylation, acetylation, and ubiquitination. We also reviewed implications of impaired metabolism of BCAA for muscle and whole-body metabolism. We comment on outstanding questions in the regulation of catabolism of these AAs, including regulation of the abundance and post-transcriptional/post-translational modification of enzymes that regulate BCAA catabolism, as well the impact of circadian rhythm, age and mTORC1 on these enzymes. Answers to such questions may facilitate emergence of treatment/management options that can help patients suffering from chronic diseases linked to impaired metabolism of the BCAAs.

scholarly journals Tissue-specific responses of branched-chain alpha-ketoacid dehydrogenase activity in metabolic acidosis.

1998 ◽  
Vol 9 (10) ◽  
pp. 1892-1898
Author(s):  
S R Price ◽  
X Wang ◽  
J L Bailey
Keyword(s):  
Amino Acid ◽  
Whole Body ◽  
Tissue Specific ◽  
Subunit Mrna ◽  
Branched Chain Amino Acid ◽  
Leucine Catabolism ◽  
Branched Chain ◽  
Ketoacid Dehydrogenase ◽  
Rate Limiting ◽  
Adrenalectomized Rats

In adrenalectomized rats, acidosis does not increase whole-body leucine oxidation unless a physiologic amount of glucocorticoids (dexamethasone) is also provided; an equivalent dose of dexamethasone without acidosis does not change leucine catabolism. Because the influences of acidification and glucocorticoids on branched-chain amino acid metabolism in specific organs are unknown, the function of branched-chain alpha-ketoacid dehydrogenase (BCKAD), the rate-limiting enzyme in branched-chain amino acid catabolism, in adrenalectomized rat skeletal muscle and liver, the two major tissues that degrade branched-chain amino acid was measured. In muscle of acidotic adrenalectomized rats receiving dexamethasone, basal and total BCKAD activities were increased 2.6- (P < 0.05) and 2.8-fold (P < 0.05), respectively. Neither acidosis nor dexamethasone alone increased these activities. BCKAD E1alpha subunit mRNA in muscle of acidotic rats given dexamethasone was increased 1.89-fold (P < 0.05) in parallel with the change in BCKAD activity; BCKAD E2 subunit mRNA was increased by acidosis, dexamethasone, or a combination of both stimuli. In contrast, basal BCKAD activity in liver of rats with acidosis or dexamethasone was nearly threefold lower (P < 0.05) and changes in enzyme activity reflected reduced subunit mRNA. Thus, there are reciprocal, tissue-specific changes in BCKAD function in response to acidosis.

Relation between transamination of branched-chain amino acids and urea synthesis: evidence from human pregnancy

1998 ◽  
Vol 275 (3) ◽  
pp. E423-E431 ◽  
Author(s):  
Satish C. Kalhan ◽  
Karen Q. Rossi ◽  
Lourdes L. Gruca ◽  
Dennis M. Super ◽  
Samuel M. Savin
Keyword(s):  
Amino Acids ◽  
Normal Pregnancy ◽  
Branched Chain Amino Acids ◽  
Whole Body ◽  
Urea Synthesis ◽  
N Metabolism ◽  
Quantitative Changes ◽  
Branched Chain ◽  
Total Body ◽  
Nutrient Administration

Protein and nitrogen (N) accretion by the mother is a major adaptive response to pregnancy in humans and animals to meet the demands of the growing conceptus. Quantitative changes in whole body N metabolism were examined during normal pregnancy by measuring the rates of leucine N ( QN) and carbon ( QC) kinetics with the use of [1-13C,15N]leucine. Rate of synthesis of urea was measured by [15N2]urea tracer. Pregnancy-related change in total body water was quantified by H2[18O] dilution, and respiratory calorimetry was performed to quantify substrate oxidation. A significant decrease in the rate of urea synthesis was evident in the 1st trimester (nonpregnant 4.69 ± 1.14 vs. pregnant 3.44 ± 1.11 μmol ⋅ kg−1⋅ min−1; means ± SD, P < 0.05). The lower rate of urea synthesis was sustained through the 2nd and 3rd trimesters. QNwas also lower in the 1st trimester during fasting; however, it reached a significant level only in the 3rd trimester (nonpregnant 166 ± 35 vs. 3rd trimester 135 ± 16 μmol ⋅ kg−1⋅ h−1; P < 0.05). There was no significant change in QCduring pregnancy. A significant decrease in the rate of transamination of leucine was evident in the 3rd trimester both during fasting and in response to nutrient administration ( P< 0.05). The rate of deamination of leucine was correlated with the rate of urea synthesis during fasting ( r = 0.59, P = 0.001) and during feeding ( r = 0.407, P = 0.01). These data show that pregnancy-related adaptations in maternal N metabolism are evident early in gestation before any significant increase in fetal N accretion. It is speculated that the lower transamination of branched-chain amino acids may be due to decreased availability of N acceptors such as α-ketoglutarate as a consequence of resistance to insulin action evident in pregnancy.

Changes in leucine kinetics during meal absorption: effects of dietary leucine availability

1986 ◽  
Vol 250 (6) ◽  
pp. E695-E701 ◽  
Author(s):  
S. Nissen ◽  
M. W. Haymond
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Branched Chain Amino Acids ◽  
Whole Body ◽  
Constant Infusion ◽  
Leucine Oxidation ◽  
Amino Acid Availability ◽  
Dietary Amino Acid ◽  
Branched Chain

Whole-body leucine and alpha-ketoisocaproate (KIC) metabolism were estimated in mature dogs fed a complete meal, a meal devoid of branched-chain amino acids, and a meal devoid of all amino acids. Using a constant infusion of [4,5-3H]leucine and alpha-[1-14C]ketoisocaproate (KIC), combined with dietary [5,5,5-2H3]leucine, the rate of whole-body proteolysis, protein synthesis, leucine oxidation, and interconversion of leucine and KIC were estimated along with the rate of leucine absorption. Ingestion of the complete meal resulted in a decrease in the rate of endogenous proteolysis, a small increase in the estimated rate of leucine entering protein, and a twofold increase in the rate of leucine oxidation. Ingestion of either the meal devoid of branched-chain amino acids or devoid of all amino acids resulted in a decrease in estimates of whole-body rates of proteolysis and protein synthesis, decreased leucine oxidation, and a decrease in the interconversion of leucine and KIC. The decrease in whole-body proteolysis was closely associated with the rise in plasma insulin concentrations following meal ingestion. Together these data suggest that the transition from tissue catabolism to anabolism is the result, at least in part, of decreased whole-body proteolysis. This meal-related decrease in proteolysis is independent of the dietary amino acid composition or content. In contrast, the rate of protein synthesis was sustained only when the meal complete in all amino acids was provided, indicating an overriding control of protein synthesis by amino acid availability.

Effect of Infused Branched-Chain Amino Acids on Muscle and Whole-Body Amino Acid Metabolism in Man

1990 ◽  
Vol 79 (5) ◽  
pp. 457-466 ◽  
Author(s):  
Rita J. Louard ◽  
Eugene J. Barrett ◽  
Robert A. Gelfand
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Branched Chain Amino Acids ◽  
Whole Body ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Branched Chain Amino Acid ◽  
Branched Chain

1. Using the forearm balance method, together with systemic infusions of l-[ring-2,6-3H]phenylalanine and l-[1-14C]leucine, we examined the effects of infused branched-chain amino acids on whole-body and skeletal muscle amino acid kinetics in 10 postabsorptive normal subjects; 10 control subjects received only saline. 2. Infusion of branched-chain amino acids caused a four-fold rise in arterial branched-chain amino acid levels and a two-fold rise in branched-chain keto acids; significant declines were observed in circulating levels of most other amino acids, including phenylalanine, which fell by 34%. Plasma insulin levels were unchanged from basal levels (8 ± 1 μ-units/ml). 3. Whole-body phenylalanine flux, an index of proteolysis, was significantly suppressed by branched-chain amino acid infusion (P < 0.002), and forearm phenylalanine production was also inhibited (P < 0.03). With branched-chain amino acid infusion total leucine flux rose, with marked increments in both oxidative and non-oxidative leucine disposal (P < 0.001). Proteolysis, as measured by endogenous leucine production, showed a modest 12% decrease, although this was not significant when compared with saline controls. The net forearm balance of leucine and other branched-chain amino acids changed from a basal net output to a marked net uptake (P < 0.001) during branched-chain amino acid infusion, with significant stimulation of local leucine disposal. Despite the rise in whole-body non-oxidative leucine disposal, and in forearm leucine uptake and disposal, forearm phenylalanine disposal, an index of muscle protein synthesis, was not stimulated by infusion of branched-chain amino acids. 4. The results suggest that in normal man branched-chain amino acid infusion suppresses skeletal muscle proteolysis independently of any rise of plasma insulin. Muscle branched-chain amino acid uptake rose dramatically in the absence of any apparent increase in muscle protein synthesis, as measured by phenylalanine disposal, or in branched-chain keto acid release. Thus, an increase in muscle branched-chain amino acid concentrations and/ or local branched-chain amino acid oxidation must account for the increased disposal of branched-chain amino acids.

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