Branched Chain Amino Acids: Beyond Nutrition Metabolism

Nie, Cunxi; He, Ting; Zhang, Wenju; Zhang, Guolong; Ma, Xi

doi:10.3390/ijms19040954

Cited by 541 publications

(408 citation statements)

References 117 publications

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“…Of note, increases in catabolism of BCAAs to CoA species by BCKDC paralleled increases in TCA cycle energetics, supporting a role of BCAA catabolic anaplerosis in “closing” TCA cycle separations and increasing immune and organ regenerative anabolic pathways. Valine and isoleucine catabolic pathways enter the TCA cycle at succinyl‐CoA and leucine at acetyl‐CoA . These findings suggest that BCAAs may play a vital and previously unrecognized role in regulating mitochondrial bioenergetics during inflammatory stress and that this process is controlled, at least in part, by the PDC/PDK axis.…”

Section: Discussionmentioning

confidence: 97%

“…Valine and isoleucine catabolic pathways enter the TCA cycle at succinyl-CoA and leucine at acetyl-CoA. 49 These findings suggest that BCAAs may play a vital and previously unrecognized role in regulating mitochondrial bioenergetics during inflammatory stress and that this process is controlled, at least in part, by the PDC/PDK axis. It is possible that both the PDC and BCKDC regulate itaconate levels, and that increases in leucine levels are required to restore repressed anabolic functions of mTOR.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Stimulating pyruvate dehydrogenase complex reduces itaconate levels and enhances TCA cycle anabolic bioenergetics in acutely inflamed monocytes

Zhu

Long

Zabalawi

et al. 2020

Journal of Leukocyte Biology

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The pyruvate dehydrogenase complex (PDC)/pyruvate dehydrogenase kinase (PDK) axis directs the universal survival principles of immune resistance and tolerance in monocytes by controlling anabolic and catabolic energetics. Immune resistance shifts to immune tolerance during inflammatory shock syndromes when inactivation of PDC by increased PDK activity disrupts the tricarboxylic acid (TCA) cycle support of anabolic pathways. The transition from immune resistance to tolerance also diverts the TCA cycle from citrate‐derived cis‐aconitate to itaconate, a recently discovered catabolic mediator that separates the TCA cycle at isocitrate and succinate dehydrogenase (SDH). Itaconate inhibits succinate dehydrogenase and its anabolic role in mitochondrial ATP generation. We previously reported that inhibiting PDK in septic mice with dichloroacetate (DCA) increased TCA cycle activity, reversed septic shock, restored innate and adaptive immune and organ function, and increased survival. Here, using unbiased metabolomics in a monocyte culture model of severe acute inflammation that simulates sepsis reprogramming, we show that DCA‐induced activation of PDC restored anabolic energetics in inflammatory monocytes while increasing TCA cycle intermediates, decreasing itaconate, and increasing amino acid anaplerotic catabolism of branched‐chain amino acids (BCAAs). Our study provides new mechanistic insight that the DCA‐stimulated PDC homeostat reconfigures the TCA cycle and promotes anabolic energetics in monocytes by reducing levels of the catabolic mediator itaconate. It further supports the theory that PDC is an energy sensing and signaling homeostat that restores metabolic and energy fitness during acute inflammation.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Stimulating pyruvate dehydrogenase complex reduces itaconate levels and enhances TCA cycle anabolic bioenergetics in acutely inflamed monocytes

Zhu

Long

Zabalawi

et al. 2020

Journal of Leukocyte Biology

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“…Although many play a role in protein synthesis, branched-chain amino acids and their derivatives are of particular importance for building and maintaining muscle mass. 36,37 Of particular note is leucine, the most important regulator of muscle growth, and its metabolite derivative b-hydroxy-b-methylbutyrate (HMB). HMB has been shown to act as a potent stimulator of protein synthesis as well as an inhibitor of protein breakdown.…”

Section: Identify and Assess Low Muscle Mass For Those At Risk Of Malmentioning

confidence: 99%

The Underappreciated Role of Low Muscle Mass in the Management of Malnutrition

Deutz

Ashurst

Ballesteros³

et al. 2019

Journal of the American Medical Directors Association

146

135

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a b s t r a c tPreserving muscle is not only crucial for maintaining proper physical movement, but also for its many metabolic and homeostatic roles. Low muscle mass has been shown to adversely affect health outcomes in a variety of disease states (eg, chronic obstructive pulmonary disease, cancer, cardiovascular disease) and leads to an increased risk for readmission and mortality in hospitalized patients. Low muscle mass is now included in the most recent diagnostic criteria for malnutrition. Current management strategies for malnutrition may not prioritize the maintenance and restoration of muscle mass. This likely reflects the challenge of identifying and measuring this body composition compartment in clinical practice and the lack of awareness by health care professionals of the importance that muscle plays in patient health outcomes. As such, we provide a review of current approaches and make recommendations for managing low muscle mass and preventing muscle loss in clinical practice. Recommendations to assist the clinician in the optimal management of patients at risk of low muscle mass include the following: (1) place muscle mass at the core of nutritional assessment and management strategies; (2) identify and assess low muscle mass; (3) develop a management pathway for patients at risk of low muscle mass; (4) optimize nutrition to focus on muscle mass gain versus weight gain alone; and (5) promote exercise and/or rehabilitation therapy to help maintain and build muscle mass. The need to raise awareness of the importance of screening and managing 'at risk' patients so it becomes routine is imperative for change to occur. Health systems need to drive clinicians to treat patients with this focused approach, and the economic benefits This opinion paper was sponsored by Abbott with all authors receiving honorarium for their contributions.

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“…Apparent digestibility coefficients of branched-chain amino acids in four small intestinal segments and their digestion rate constants in birds offered sorghum-based diets (adapted from [44]). Three reviews provide instructive insights into the complexities of both leucine per se and the BCAAs in general [110][111][112]. The notion that the requirements for amino acids that are typically present in more than adequate amounts in broiler diets may not be adequately identified has been advanced [113].…”

Section: Branched-chain Amino Acids: Isoleucine Leucine and Valinementioning

confidence: 99%

Synthetic and Crystalline Amino Acids: Alternatives to Soybean Meal in Chicken-Meat Production

Selle

Dorigam

Lemme

et al. 2020

Animals

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Simple Summary: There is a distinct possibility that synthetic and crystalline, or non-bound, amino acids will partially replace soybean meal in diets for broiler chickens and reduce the dependency of the chicken-meat industry on soybean meal as its principal source of protein.The genesis of this partial replacement will be the successful development of reduced-crude protein diets. A reduced-crude protein diet contains less soybean meal, and therefore less crude protein, but an increased array of essential and even non-essential non-bound amino acids so that requirements are met. There are, however, several challenges to be overcome if reduced-crude protein diets are to be successfully developed and adopted.Abstract: This review explores the premise that non-bound (synthetic and crystalline) amino acids are alternatives to soybean meal, the dominant source of protein, in diets for broiler chickens. Non-bound essential and non-essential amino acids can partially replace soybean meal so that requirements are still met but dietary crude protein levels are reduced. This review considers the production of non-bound amino acids, soybeans, and soybean meal and discusses the concept of reduced-crude protein diets. There is a focus on specific amino acids, including glycine, serine, threonine, and branched-chain amino acids, because they may be pivotal to the successful development of reduced-crude protein diets. Presently, moderate dietary crude protein reductions of approximately 30 g/kg are feasible, but more radical reductions compromise broiler performance. In theory, an 'ideal' amino acid profile would prevent this, but this is not necessarily the case in practice. The dependence of the chicken-meat industry on soybean meal will be halved if crude protein reductions in the order of 50 g/kg are attained without compromising the growth performance of broiler chickens. In this event, synthetic and crystalline, or non-bound, amino acids will become viable alternatives to soybean meal in chicken-meat production.Animals 2020, 10, 729 2 of 20 generates 1.1 kg CO 2 equivalents, which is considerably less than that of pork (3.8 kg CO 2 equivalents) or beef (14.8 kg CO 2 equivalents) production [2]. Moreover, it has been predicted that chicken-meat production will contribute 7.1% of greenhouse gas emissions compared to 29.8% and 63.1% for pork and beef, respectively [2]. However, diets for broiler chickens may contain more than 200 g/kg protein, the majority of which is derived from soybean meal; consequently, the chicken-meat industry has a huge demand for soybean meal. The production of 1 kg of chicken meat will require an input in the order of 560 g soybean meal given a conservative 250 g/kg dietary inclusion of soybean meal and a 2.25:1 conversion of feed into carcass weight. Importantly, this demand can be diminished by inclusions of non-bound (synthetic and crystalline) amino acids in broiler diets at the expense of soybean meal via the successful development of reduced-crude protein (CP) diets [3]. Therefore, synthetic...

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Branched Chain Amino Acids: Beyond Nutrition Metabolism

Cited by 541 publications

References 117 publications

Stimulating pyruvate dehydrogenase complex reduces itaconate levels and enhances TCA cycle anabolic bioenergetics in acutely inflamed monocytes

Stimulating pyruvate dehydrogenase complex reduces itaconate levels and enhances TCA cycle anabolic bioenergetics in acutely inflamed monocytes

The Underappreciated Role of Low Muscle Mass in the Management of Malnutrition

Synthetic and Crystalline Amino Acids: Alternatives to Soybean Meal in Chicken-Meat Production

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