Alterations in protein and amino acid metabolism in rats fed a branched-chain amino acid- or leucine-enriched diet during postprandial and postabsorptive states

Nutrition & Metabolism, Feb 2016

Background Many people believe in favourable effects of branched-chain amino acids (BCAAs; valine, leucine, and isoleucine), especially leucine, on muscle protein balance and consume BCAAs for many years. We determined the effects of the chronic intake of a BCAA- or leucine-enriched diet on protein and amino acid metabolism in fed and postabsorptive states. Methods Rats were fed a standard diet, a diet with a high content of valine, leucine, and isoleucine (HVLID), or a high content of leucine (HLD) for 2 months. Half of the animals in each group were sacrificed in the fed state on the last day, and the other half were sacrificed after overnight fast. Protein synthesis was assessed using the flooding dose method (L-[3,4,5- 3 H]phenylalanine), proteolysis on the basis of chymotrypsin-like activity (CHTLA) of proteasome and cathepsin B and L activities. Results Chronic intake of HVLID or HLD enhanced plasma levels of urea, alanine and glutamine. HVLID also increased levels of all three BCAA and branched-chain keto acids (BCKA), HLD increased leucine, ketoisocaproate and alanine aminotransferase and decreased valine, ketovaline, isoleucine, ketoisoleucine, and LDL cholesterol. Tissue weight and protein content were lower in extensor digitorum longus muscles in the HLD group and higher in kidneys in the HVLID and HLD groups. Muscle protein synthesis in postprandial state was higher in the HVLID group, and CHTLA was lower in muscles of the HVLID and HLD groups compared to controls. Overnight starvation enhanced alanine aminotransferase activity in muscles, and decreased protein synthesis in gastrocnemius (in HVLID group) and extensor digitorum longus (in HLD group) muscles more than in controls. Effect of HVLID and HLD on CHTLA in muscles in postabsorptive state was insignificant. Conclusions The results failed to demonstrate positive effects of the chronic consumption of a BCAA-enriched diet on protein balance in skeletal muscle and indicate rather negative effects from a leucine-enriched diet. The primary effects of both diets are an activated catabolism of BCAAs, which leads to an enhanced production of BCKA, alanine and glutamine and their utilization in visceral tissues and an impaired protein synthesis in postabsorptive state, particularly in fast-twitch (white) muscles.

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Alterations in protein and amino acid metabolism in rats fed a branched-chain amino acid- or leucine-enriched diet during postprandial and postabsorptive states

Holecek et al. Nutrition & Metabolism Alterations in protein and amino acid metabolism in rats fed a branched-chain amino acid- or leucine-enriched diet during postprandial and postabsorptive states Milan Holecek 0 Pavel Siman 2 Melita Vodenicarovova 0 Roman Kandar 1 0 Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University in Prague , Simkova 870, Hradec Kralove 500 38 , Czech Republic 1 Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice , Pardubice , Czech Republic 2 Department of Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University Prague , Hradec Kralove , Czech Republic Background: Many people believe in favourable effects of branched-chain amino acids (BCAAs; valine, leucine, and isoleucine), especially leucine, on muscle protein balance and consume BCAAs for many years. We determined the effects of the chronic intake of a BCAA- or leucine-enriched diet on protein and amino acid metabolism in fed and postabsorptive states. Methods: Rats were fed a standard diet, a diet with a high content of valine, leucine, and isoleucine (HVLID), or a high content of leucine (HLD) for 2 months. Half of the animals in each group were sacrificed in the fed state on the last day, and the other half were sacrificed after overnight fast. Protein synthesis was assessed using the flooding dose method (L-[3,4,5-3H]phenylalanine), proteolysis on the basis of chymotrypsin-like activity (CHTLA) of proteasome and cathepsin B and L activities. Results: Chronic intake of HVLID or HLD enhanced plasma levels of urea, alanine and glutamine. HVLID also increased levels of all three BCAA and branched-chain keto acids (BCKA), HLD increased leucine, ketoisocaproate and alanine aminotransferase and decreased valine, ketovaline, isoleucine, ketoisoleucine, and LDL cholesterol. Tissue weight and protein content were lower in extensor digitorum longus muscles in the HLD group and higher in kidneys in the HVLID and HLD groups. Muscle protein synthesis in postprandial state was higher in the HVLID group, and CHTLA was lower in muscles of the HVLID and HLD groups compared to controls. Overnight starvation enhanced alanine aminotransferase activity in muscles, and decreased protein synthesis in gastrocnemius (in HVLID group) and extensor digitorum longus (in HLD group) muscles more than in controls. Effect of HVLID and HLD on CHTLA in muscles in postabsorptive state was insignificant. Conclusions: The results failed to demonstrate positive effects of the chronic consumption of a BCAA-enriched diet on protein balance in skeletal muscle and indicate rather negative effects from a leucine-enriched diet. The primary effects of both diets are an activated catabolism of BCAAs, which leads to an enhanced production of BCKA, alanine and glutamine and their utilization in visceral tissues and an impaired protein synthesis in postabsorptive state, particularly in fast-twitch (white) muscles. Nutritional supplements; Glutamine; Protein synthesis; Proteolysis; Muscle; Starvation Background The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are essential substrates and important regulators in the synthesis of body proteins, substrates for energy production and precursors for the formation of other amino acids. The stimulatory effect of BCAAs on protein synthesis and the inhibitory effect on proteolysis have been known for many years [ 1–3 ]. Particularly, leucine was implicated in the stimulation of protein synthesis in skeletal muscle. Leucine enhances insulin release from β-cells of the pancreas and directly stimulates protein synthesis through the mammalian target of rapamycin (mTOR) signalling pathway and the phosphorylation of translation initiation factors and ribosomal proteins [ 4, 5 ]. The inhibitory effect of BCAAs on proteolysis is likely mediated by several metabolites of BCAAs, particularly branched-chain keto acids and beta-hydroxy-beta-methylbutyrate [ 6, 7 ]. The initial site for most BCAA catabolism is skeletal muscle because of the high activity of BCAA aminotransferase, which enables the transfer of the amino group of BCAAs to α-ketoglutarate to form glutamate and branched-chain keto acids (BCKA), i.e., αketoisocaproate (KIC, ketoleucine), α-keto-β-methylvalerate (KMV, ketoisoleucine) and α-ketoisovalerate (KIV, ketovaline). The enhanced availability of glutamic acid increases the flux through glutamine synthetase and alanine aminotransferase leading to enhanced synthesis of glutamine and alanine. These amino acids are released together with most of the BCKA from skeletal muscle to the blood [ 8–10 ]. Overall, an enhanced intake of BCAAs should lead to enhanced BCAA catabolism and the release of glutamine, alanine and BCKA from muscles to the blood stream (Fig. 1). The unique effects of BCAAs on protein metabolism led to the use of BCAAs in patients with cachectic disorders and as popular dietary supple (...truncated)


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Milan Holecek, Pavel Siman, Melita Vodenicarovova, Roman Kandar. Alterations in protein and amino acid metabolism in rats fed a branched-chain amino acid- or leucine-enriched diet during postprandial and postabsorptive states, Nutrition & Metabolism, 2016, pp. 12, 13, DOI: 10.1186/s12986-016-0072-3