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.
Much is known about the positive effects of branched‐chain amino acids (BCAA) in regulating muscle protein metabolism. Comparatively much less is known about the effects of these amino acids and their metabolites in regulating myotube formation. Using cultured myoblasts, we showed that although leucine is required for myotube formation, this requirement is easily met by α‐ketoisocaproic acid, the ketoacid of leucine. We then demonstrated increases in the expression of the first two enzymes in the catabolism of the three BCAA, branched‐chain amino transferase (BCAT2) and branched‐chain α‐ketoacid dehydrogenase (BCKD), with ~3× increase in BCKD protein expression (p < .05) during differentiation. Furthermore, depletion of BCAT2 abolished myoblast differentiation, as indicated by reduction in the levels of myosin heavy chain‐1, troponin and myogenin. Supplementation of incubation medium with branched‐chain α‐ketoacids or related metabolites derivable from BCAT2 functions did not rescue the defects. However, co‐depletion of BCKD kinase partially rescued the defects. Collectively, our data indicate a requirement for BCAA catabolism during myotube formation and that this requirement for BCAT2 likely goes beyond the need for this enzyme to generate the α‐ketoacids of the BCAA.
1. Under normal English storage conditions, the heat production of mature potatoes drops rapidly from a value of probably about 150 b.th.u./ton/hr. immediately after harvest to about 30–50 b.th.u./ton/hr. Sprouting is accompanied by an increase in the rate of heat production. The initial heat production of immature potatoes may be of the order of 250 b.th.u./ton/hr.2. As a result of the production of heat, the temperatures in stacks of potatoes will tend to rise to levels above that of the outside air which are just sufficient to cause the convection and conduction necessary to remove the metabolic heat as fast as it is produced.3. The difference in temperature between the potatoes and the ambient air is a function of the heat production of the potatoes and of the height of the stack, and is practically independent of its other dimensions if these exceed twice the height. Under average conditions during the middle of the storage season, and for heights of storage of from about 6 to 12 ft. it may be taken as a rough practical guide that the average and maximum temperatures of the potatoes will tend to exceed the average temperature of the store air by about 2/3 and 1° F. respectively for every foot of height.4. Overheating is possible at both the beginning and end of the storage season, when heat production is high and the outside temperatures also possibly high. In general it is safe to store unventilated potatoes to a height of about 6 ft. if they are mature, though if they are harvested with a great deal of earth late storage should not be attempted. If there is no intention of storing late, and the potatoes are fairly clean, storage to aheight of 12 ft. may be permissible. Immature potatoes should not be stored to a height of more than 3 ft.
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