Glucocorticoid-mediated activation of muscle branched-chain alpha-keto acid dehydrogenase in vivo

Block, Kevin P.; Richmond, Wendy; Mehard, William B.; Buse, Maria G.

doi:10.1152/ajpendo.1987.252.3.e396

Cited by 22 publications

(15 citation statements)

References 18 publications

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“…The BCAA catabolic pathway has a rate-limiting enzyme, the branched chain keto acid dehydrogenase, catalysing deamination of leucine to KIC. The activity of this enzyme in the presence of high insulin concentrations, or low concentrations of BCAA and its intermediates (as in this study: 20% lower leucine and 48% lower KIC), is reduced or inhibited, sparing the BCAA (Block et al, 1987). Despite this, there was no difference in CO 2 concentration, suggesting no change in LO.…”

Section: Discussionsupporting

confidence: 50%

Insulin regulation of amino-acid metabolism in the mammary gland of sheep in early lactation and fed fresh forage

Sinclair

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Davis

et al. 2009

Animal

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Insulin plays an important role in regulating the partitioning of nutrients to the mammary gland, particularly in lactating ruminants fed concentrate-based diets. There is evidence that the nutritional status of the animals might also affect their response to insulin. This is largely untested in early lactating ruminants fed fresh forage. To investigate nutritional effects on insulin response, 12 lactating sheep, housed indoors, were allocated to one of two treatment groups (hyperinsulinaemic euglycaemic clamp (HEC) or control) in a randomised block design and fed perennial ryegrass (Lolium perenne)/white clover (Trifolium repens) pasture. Mammary amino acid (AA) net uptake from plasma and utilisation for milk protein synthesis was measured during the 4th day of the HEC using arterio-venous concentration differences, and 1-13 C-leucine was used to estimate whole body and mammary gland leucine kinetics. There was no change in feed intake, milk protein output and mammary blood flow during the HEC ( P . 0.1). The HEC decreased ( P , 0.1) the arterial concentrations of all essential AA (EAA) except histidine. The mammary net uptake of some EAA (isoleucine, leucine, methionine and phenylalanine) was reduced by the HEC ( P , 0.1). Leucine oxidation in the mammary gland was not altered during the HEC ( P . 0.1) but mammary protein synthesis was reduced by the HEC ( P , 0.05). These results show that sheep mammary gland can adapt to changing AA precursor supply to maintain milk protein production during early lactation, when fed fresh forage. How this occurs remains unclear, and this area deserves further study.

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Section: Discussionsupporting

confidence: 50%

Insulin regulation of amino-acid metabolism in the mammary gland of sheep in early lactation and fed fresh forage

Sinclair

Back

Davis

et al. 2009

Animal

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“…Numerous investigators have considered BCKDHC to be the rate-determining enzyme in BCAA oxidation (33)(34)(35)(36)(37). According to metabolic control theory, if BCKDHC were rate-determining, down-regulation of its activity would be expected to result in accumulation of its substrates (38).…”

Section: Discussionmentioning

confidence: 99%

Adipose Tissue Branched Chain Amino Acid (BCAA) Metabolism Modulates Circulating BCAA Levels

Herman

She

Peroni

et al. 2010

Journal of Biological Chemistry

334

310

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Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent observations demonstrating down-regulation of BCAA oxidation enzymes in adipose tissue in obese and insulin-resistant humans. Using gene set enrichment analysis, we observe alterations in adipose-tissue BCAA enzyme expression caused by adipose-selective genetic alterations in the GLUT4 glucosetransporter expression. We show that the rate of adipose tissue BCAA oxidation per mg of tissue from normal mice is higher than in skeletal muscle. In mice overexpressing GLUT4 specifically in adipose tissue, we observe coordinate down-regulation of BCAA metabolizing enzymes selectively in adipose tissue. This decreases BCAA oxidation rates in adipose tissue, but not in muscle, in association with increased circulating BCAA levels. To confirm the capacity of adipose tissue to modulate circulating BCAA levels in vivo, we demonstrate that transplantation of normal adipose tissue into mice that are globally defective in peripheral BCAA metabolism reduces circulating BCAA levels by 30% (fasting)-50% (fed state). These results demonstrate for the first time the capacity of adipose tissue to catabolize circulating BCAAs in vivo and that coordinate regulation of adiposetissue BCAA enzymes may modulate circulating BCAA levels.The branched chain amino acids (BCAAs) 2 , leucine, isoleucine, and valine, are three of the nine essential amino acids and are relatively abundant in the food supply accounting for ϳ20% of total protein intake (1). In contrast to the other 17 amino acids, which are predominantly metabolized in the liver, BCAAs are poorly metabolized during first pass through the liver as the liver expresses only low levels of the mitochondrial branched chain aminotransferase (BCAT2 or BCATm), the first enzyme in the catabolism of BCAAs in most peripheral tissues (2, 3). BCAAs are therefore in a unique position among amino acids to signal to the periphery and the brain the amino acid content of a meal. Circulating BCAAs, acting as nutrient signals, regulate protein synthesis, and degradation, and insulin secretion, and have been implicated in central nervous system control of food intake and energy balance (4 -7). Our knowledge of the physiologic mechanisms which regulate circulating BCAA levels remains incomplete. In this study, we provide evidence that adipose tissue contributes to the regulation of circulating BCAAs.Over the last two decades, adipose tissue has emerged as a key endocrine organ and a regulator of integrated fuel homeostasis. Whereas its role in glucose and lipid homeostasis is widely recognized, its role in systemic protein ...

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“…Secondly, liver protein and amino acid turnover is very rapid (4-5 times that of white muscle; Narayansingh and Eales (1975)) suggesting that significant proteolysis can occur, releasing free amino acids, in the absence of any detectable change in total protein (Walton and Cowey 1982). Thirdly, similar increases in the plasma BCAAs are seen after exercise and acute (within 2h) cortisol elevation in mammals and here liver is the primary source (Block et al 1987;Wagenmakers et al 1989;MacLean et al 1991). The increase in plasma BCAAs is clearly indicative of proteolysis, since these are essential amino acids (i.e., the increase could not be due to synthesis).…”

Section: Mobilization Of Bcaasmentioning

confidence: 95%

“…5). Rapid, short-term glucocorticoid elevation in rats has been shown to increase muscle BCAA oxidation (Block et al 1987). Within 2h of receiving a single injection of 6-a-methylprednisolone (a water soluble glucocorticoid with rapid effects), there were significant increases in muscle and plasma BCAAs and muscle branched-chain keto acid dehydrogenase activity, due to increases in the unphosphorylated or active form of the enzyme (#4, Fig.…”

Section: Oxidation Of Bcaas In White Musclementioning

confidence: 99%

The role of cortisol in amino acid mobilization and metabolism following exhaustive exercise in rainbow trout (Oncorhynchus mykiss Walbaum)

Milligan

1997

Fish Physiol Biochem

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The role of cortisol in the mobilization and metabolism of amino acids following exhaustive exercise in rainbow trout (Oncorhynchus mykiss) was investigated. Plasma cortisol levels were elevated for 4h following exercise and 6, of a total of 22 amino acids, showed significant responses. In white muscle, alanine and glutamine were elevated immediately after exercise through to 4h, whereas glutamate, and the branchedchain amino acids (BCAA), isoleucine, leucine and valine, all decreased over this time. In plasma all of these amino acids increased from 2-4h post-exercise, while in liver, alanine and glutamine increased, glutamate did not change and the BCAAs declined over this time. Blockade of the post-exercise elevation in plasma cortisol with either metyrapone (cortisol synthesis inhibitor) or dexamethasone (cortisol release blocker) prevented the changes in tissue amino acid levels. This study demonstrates that cortisol can act rapidly (within minutes to hours) to alter amino acid metabolism in fish. A model is presented to explain the action of cortisol on amino acid metabolism.

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Glucocorticoid-mediated activation of muscle branched-chain alpha-keto acid dehydrogenase in vivo

Cited by 22 publications

References 18 publications

Insulin regulation of amino-acid metabolism in the mammary gland of sheep in early lactation and fed fresh forage

Insulin regulation of amino-acid metabolism in the mammary gland of sheep in early lactation and fed fresh forage

Adipose Tissue Branched Chain Amino Acid (BCAA) Metabolism Modulates Circulating BCAA Levels

The role of cortisol in amino acid mobilization and metabolism following exhaustive exercise in rainbow trout (Oncorhynchus mykiss Walbaum)

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