Enhanced Glutamine Availability Exerts Different Effects on Protein and Amino Acid Metabolism in Skeletal Muscle From Healthy and Septic Rats

Background: Enhanced glutamine (GLN) intake may affect the catabolism of branched‐chain amino acids (BCAAs; valine, leucine, and isoleucine), which play a regulatory role in protein turnover. We examined the effects of enhanced GLN availability on leucine oxidation, amino acid concentrations, and protein metabolism in muscles from healthy and septic rats. Methods: Cecal ligation and puncture were used as a model of sepsis. Twenty‐four hours after surgery, the soleus (SOL, red muscle) and the extensor digitorum longus (EDL, white muscle) were incubated in medium containing 0.5 or 2.0 mM GLN. Protein breakdown, protein synthesis, and leucine oxidation were determined via 3‐methylhistidine release, muscle L‐[1‐¹⁴C]leucine radioactivity, and the radioactivity of released ¹⁴CO₂, respectively. Results: In muscles from septic animals, increased proteolysis and leucine oxidation and decreased protein synthesis were detected. These effects were more pronounced in the EDL. In septic muscles, the addition of GLN decreased leucine oxidation in both muscles and increased protein synthesis in the EDL. In muscles from untreated animals, decreased leucine oxidation after the addition of GLN to the medium was associated with decreased protein synthesis in the SOL and decreased concentrations of serine, glycine, histidine, alanine, arginine, proline, and lysine in both muscles. Conclusions: White muscle fibers are more sensitive to septic stimuli than red fibers are. In sepsis, enhanced GLN intake may ameliorate GLN deficiency, inhibit BCAA catabolism, and stimulate protein synthesis. In the healthy state, surplus of GLN may lead to severe alterations in the intramuscular concentration of several amino acids and impair protein synthesis.     

Leucine and protein synthesis: mTOR and beyond

The effects of amino acid intake on protein synthesis in the intact rat appear to be mediated almost entirely by a single amino acid: leucine. The effect of leucine on protein synthesis appears to be closely associated with eIF4G phosphorylation and its association with eIF4E, but whether eIF4G phosphorylation actually mediates the effects of leucine or is merely associated with these events has not been elucidated. Additional research is needed to determine whether leucine effects eIF4G phosphorylation, whether eIF4G phos-phorylation is essential for the effect of leucine on protein synthesis, and whether mTOR (mammalian target of rapamycin) or another component of the mTOR complex is somehow involved in leucine-specific signaling.     

Insulinotropic and Muscle Protein Synthetic Effects of Branched-Chain Amino Acids: Potential Therapy for Type 2 Diabetes and Sarcopenia

The loss of muscle mass and strength with aging (i.e., sarcopenia) has a negative effect on functional independence and overall quality of life. One main contributing factor to sarcopenia is the reduced ability to increase skeletal muscle protein synthesis in response to habitual feeding, possibly due to a reduction in postprandial insulin release and an increase in insulin resistance. Branched-chain amino acids (BCAA), primarily leucine, increases the activation of pathways involved in muscle protein synthesis through insulin-dependent and independent mechanisms, which may help counteract the “anabolic resistance” to feeding in older adults. Leucine exhibits strong insulinotropic characteristics, which may increase amino acid availability for muscle protein synthesis, reduce muscle protein breakdown, and enhance glucose disposal to help maintain blood glucose homeostasis.     

Meal-induced thermogenesis and macronutrient oxidation in lean and obese women after consumption of carbohydrate-rich and fat-rich meals

Objective

To examine differences in meal-induced thermogenesis and macronutrient oxidation between lean and obese women after consumption of two different isocaloric meals, one rich in carbohydrate (CHO) and one rich in fat.

Methods

A total of 19 lean and 22 obese women were studied on two occasions, 1 wk apart. In one visit they consumed a CHO-rich meal and in the other visit a fat-rich meal. The two meals were isocaloric and were given in random order. Resting energy expenditure and macronutrient oxidation rates were measured and calculated in the fasting state and every hour for 3 h after meal consumption.

Results

Meal-induced thermogenesis was not different between lean and obese subjects after the CHO-rich (P = 0.89) or fat-rich (P = 0.32) meal, but it was significantly higher after the CHO-rich compared with the fat-rich meal in the lean and the obese individuals (P < 0.05). Protein oxidation rate increased slightly but significantly after the test meals in both groups (P < 0.01). Fat oxidation rate decreased after consumption of the CHO-rich meal (P < 0.001), whereas it increased after consumption of the fat-rich meal in both groups (P < 0.01). CHO oxidation rate increased in both groups after consumption of the CHO-rich meal (P < 0.001). Oxidation rates of protein, fat, and CHO during the experiment were not significantly different between lean and obese participants.

Conclusion

Meal-induced thermogenesis and macronutrient oxidation rates were not significantly different between lean and obese women after consumption of a CHO-rich or a fat-rich meal.     

PALMITATE AND PROTEIN SYNTHESIS IN CARDIAC MUSCLE

Fatty acids maintain protein synthesis in the heart muscle of normal and diabetic rats perfused in vitro, even in the absence of circulating insulin.     

Association between dietary branched-chain amino acid intake and skeletal muscle mass index among Korean adults: Interaction with obesity

BACKGROUND/OBJECTIVESThe branched-chain amino acids (BCAA), including isoleucine, leucine, and valine, promote muscle protein synthesis. However, obesity may interfere with protein synthesis by dysregulating mitochondrial function in the muscles. This study aimed to examine the association between dietary intake levels of BCAA and skeletal muscle mass index (SMI) in middle-aged participants, and the effect of obesity/abdominal obesity on this association.SUBJECTS/METHODSThe data of 3,966 men and women aged 50–64 years who participated in the 2008–2011 Korea National Health and Nutrition Examination Survey were analyzed. Intake levels of energy-adjusted dietary amino acids were obtained using a 24-hour dietary recall. SMI was calculated by dividing the appendicular skeletal muscle mass by body weight (kg) and multiplying the result by 100%. Multivariable general linear models were used to analyze the association of dietary BCAA intake levels with SMI.RESULTSThe beneficial effects of energy-adjusted dietary BCAA intakes on SMI were greater in the non-obesity/non-abdominal obesity groups; however, no significant associations were observed in the obesity/abdominal obesity groups (P > 0.05).CONCLUSIONSHealthy weight and sufficient intake of dietary BCAA are recommended to maintain muscle mass.     

Chemical composition,protein profile and physicochemical properties of whey protein concentrate ingredients enriched in α-lactalbumin

The objective of this study was to complete a comprehensive evaluation of the nutritional composition, physicochemical properties and protein profile of three different whey protein concentrate ingredients enriched in α-lactalbumin (LAC). The LAC ingredients studied were manufactured using different enrichment approaches, namely membrane filtration (LAC-M), selective precipitation (LAC-P) and ion exchange (LAC-IE), and were compared to benchmark whey protein concentrate (WPC) and skim milk powder (SMP) ingredients with unaltered protein profile. The LAC ingredients had heterogeneous chemical composition and protein profile, which depended on the enrichment approach used. Protein profile of LAC ingredients was dominant in α-lactalbumin and therefore higher in tryptophan when compared to the benchmark ingredients. Unlike LAC-M and LAC-IE, LAC-P had a very complex protein profile. The new information provided by this study for these novel added-value whey protein ingredients will support the development of next-generation dairy-based formulated nutritional products.     

Higher Branched-Chain Amino Acid Intake Is Associated with Handgrip Strength among Korean Older Adults

Sarcopenia is a disease of old age characterized by decreased muscle mass and strength. Branched-chain amino acids (BCAAs) promote muscle mass synthesis and increase muscle strength. We aimed to develop a dietary amino acid database and to examine the association between BCAA intake and handgrip strength in Korean older adults. Data from the Korea National Health and Nutrition Examination Survey 2014–2018 were used. Overall, 4852 participants aged ≥65 years were included in the study. Demographic, lifestyle, and health data were obtained through interviews and questionnaires. The 24-h recall method was used to assess dietary intake. An amino acid database was established using the 9th revision of the Korean Standard Food Composition Table. The mean handgrip strength was estimated from triplicate measurements obtained using the dominant hand. Multivariable linear regression analysis was performed to assess the association between BCAA intake and handgrip strength. Grains greatly contributed to amino acid intake; however, a significant negative association was observed between handgrip strength and increased BCAA intake through grains. In the fully adjusted model, leucine intake and handgrip strength showed a positive association. Thus, consuming BCAAs (especially leucine) via a variety of food sources can help maintain muscle health in older people.     

METABOLISM OF ALPHA-KETO ANALOGUES OF ESSENTIAL AMINO ACIDS

Perfusion of alpha-keto analogues of essential amino acids into isolated rat liver and skeletal muscle results in significant increases in the respective amino acids in the perfusion fluid.     

水解乳清蛋白对生长期大鼠氮代谢影响的研究

目的:观察水解乳清蛋白对生长期大鼠氮代谢的影响. 方法:40只大鼠随机分为实验组和对照组.实验组饲料氮源为水解乳清蛋白(乳清蛋白肽),对照组饲料氮源为浓缩乳清蛋白(未水解乳清蛋白).主要观察指标为蛋白质功效比值( PER)、蛋白质表观消化率(AD)和动物体重变化情况. 结果:实验组大鼠PER和AD值均显著高于对照组,实...     

Parenteral Amino Acid Intakes in Critically Ill Children

Background: Parenteral and enteral amino acid requirements for nutrition balance and function have not been defined in critically ill children or adults. In addition to playing a role in protein synthesis, amino acids trigger signaling cascades that regulate various aspects of fuel and energy metabolism and serve as precursors for important substrates. Amino acids can also be toxic. In this study, parenteral intakes of essential and nonessential amino acids (EAAs and NEAAs) supplied to critically ill children were assessed as an initial step for further studies aimed at establishing parenteral amino acid requirements. Methods: A retrospective review was conducted to assess intakes of parenteral amino acid for 116 critically ill children, and these intakes were compared with EAA intakes recommended by the Institute of Medicine. Because there are no recommended intakes for NEAA, NEAA intakes were compared with mixed muscle protein content in the older children and breast milk amino acid content in the infants. Results: Parenteral EAAs were provided in amounts that exceeded recommended intakes for healthy children, except for phenylalanine and methionine, which although excessive, were given in less generous amounts. NEAAs were supplied in lower or higher amounts than the content of mixed muscle proteins or breast milk. Parenteral amino acid formulas are limited in taurine, glutamine, and asparagine despite the fact that inflammatory/immune proteins are rich in these amino acids. Conclusions: Amino acid composition of parenteral formulas is variable and lacks scientific support. Parenteral amino acid intakes should be based on measured requirements to maintain nutrition and functional balance and on knowledge of toxicity.     

Effect of corn gluten and its hydrolysate consumptions on weight reduction in rats fed a high-fat diet

This study examined the effects of corn gluten (CG) and its hydrolysate consumptions on weight reduction in rats fed a high-fat diet. Eight-month-old male Sprague-Dawley rats (n=40) were fed a high-fat diet (40% calorie as fat) for 4 weeks. They were then randomly divided into four groups and fed the isocaloric diets with different protein sources for 8 weeks. The protein sources were casein (control group), intact CG (CG group), CG hydrolysate A (CGHA group, 30% of protein as peptides and 70% as free amino acids) and CG hydrolysate P (CGHP group, 93% of protein as peptides and 7% as free amino acids). Body weight gain, adipose tissue weights, nitrogen balance, absorptions of energy, protein and fat, lipid profiles in plasma, liver and feces and hepatic activities of carnitine palmitoyl transferase (CPT), fatty acid synthase (FAS), malic enzyme (ME) and glucose-6-phosphate dehydrogenase (G6PDH) were assessed. The CGHA diet had the highest amount of BCAAs, especially leucine, and most of them existed as free amino acid forms. The CGHA group showed significant weight reduction and negative nitrogen balance. Protein absorption and apparent protein digestibility in the CGHA group were significantly lower than those in other groups. Adipose tissue weights were the lowest in the CGHA group. Activity of CPT tended to be higher in the CGHA group than in other groups and those of FAS, ME and G6PDH were significantly lower in the CGHA group than in other groups. In conclusion, the CGHA diet which had relatively high amounts of free amino acids and BCAAs, especially leucine, had a weight reduction effect by lowering adipose tissue weight and the activities of FAS, ME and G6PDH in experimental animals, but it seemed to be a negative result induced by lowering protein absorption, increasing urinary nitrogen excretion and protein catabolism.     

Nonimprovement of healing of jejunal anastomoses by exogenous amino acids in protein depleted rats

The healing rate, as measured by bursting strength in 5 days of jejunal anastomoses in protein depleted rats is not improved by a) feeding stock diet rather than protein free diet following surgery or b) infusing a total parenteral nutrition (TPN) solution known to improve the healing rate of jejunal anastomoses in normal rats rather than either a standard TPN solution or 5% glucose.     

Predicting integrated protein nutritional quality Part 2: Integrated protein nutritional quality predicted from Amino Acid Availability Corrected Amino Acid Score (AACAAS)

An important goal in protein nutrition is the development of a reliable in vitro assay for measuring overall nutritional quality. Such an assay would be based on the assumption that quality depends on the content and availability of essential amino acids, values of which should be measurable in vitro. However, prior to development of such an assay, it is necessary to elucidate a quantitative relationship between available essential amino acid content measured in an animal model and overall quality measured in the same animal model. In the research reported here, it was found that for a group of four actual and a theoretically ideal protein, a simple linear relationship exists between Amino Acid Availability Corrected Amino Acid Score (AAACAAS) and the non-linear protein intake-response saturation kinetics parameters K_0.5 and K_0.5/n. Thus, it was possible to predict response at any intake of the five proteins and protein quality at any intake/response point.     

An Examination of Serum Acylcarnitine and Amino Acid Profiles at Different Time Point of Ketogenic Diet Therapy and Their Association of Ketogenic Diet Effectiveness

Background: This study aimed to identify metabolic parameters at different time points of ketogenic diet therapy (KDT) and investigate their association with response to KDT in pediatric drug-resistant epilepsy (DRE). Methods: Prospectively, twenty-nine patients (0.67~20 years old) with DRE received classic ketogenic diet with non-fasting, gradual KD initiation protocol (GRAD-KD) for 1 year were enrolled. A total of 22 patients remaining in study received blood examinations at baseline, 3rd, 6th, 9th, and 12th months of KDT. β-hydroxybutyrate, free carnitine, acylcarnitines, and amino acids were compared between responders (seizure reduction rate ≥ 50%) and non-responders (seizure reduction rate < 50%) to identify the effectiveness of KDT. Results: The 12-month retention rate was 76%. The responders after 12 months of KDT were 59% (13/22). The free carnitine level decreased significantly at 9th months (p < 0.001) but increased toward baseline without symptoms. Propionyl carnitine (C3), Isovaleryl carnitine (C5), 3-Hydroxyisovalerylcarnitine (C5:OH) and methylmalonyl carnitine (C4-DC) decreased but 3-hydroxybutyrylcarnitine (C4:OH) increased significantly at 12th months of KDT. The glycine level was persistently higher than baseline after KDT. KDT responders had lower baseline C3 and long-chain acylcarnitines, C14 and C18, as well as lower C5, C18, and leucine/isoleucine. Conclusions: KDT should be avoided in patients with non-ketotic hyperglycemia. Routine carnitine supplementation is not recommended because hypocarnitinemia was transient and asymptomatic during KDT. Better mitochondrial βoxidation function associates with greater KDT response.     

Muscle Protein Catabolism In Cirrhotic Patients Reduced By Branched-Chain Amino Acids

Amino acid solutions rich in branched-chain amino acids infused in six patients with cirrhosis of the liver reduced rates of protein catabolism in muscle as determined by the urinary excretion of 3-methylhistidine.     

Effect of dietary protein or amino acids on the rapid change in plasma zinc concentration in rats fed zinc deficient diets

The effects of dietary protein or amino acids on the rapid fall in plasma zinc concentration was studied in rats fed zinc deficient diets. After a 24 hr. fast, young (100 g) rats were given access to a single zinc deficient meal containing various amounts and types of protein or amino acids. Sixteen hours later, plasma zinc levels were determined. EDTA-treated soy protein, egg white and an amino acid mixture, when fed as 20% of the test meal, caused a significant (P<0.05) depression of plasma zinc concentration compared to rats given the zinc deficient meal without protein or amino acids. Plasma zinc could also be significantly lowered (P<0.05) under these conditions by a variety of absorbable chelating agents fed at 2% of the test meal. The effect of dietary protein on plasma zinc concentration could not be attributed to increased urinary zinc excretion in these studies.     

Dietary protein and calcium loss; a review

For several decades, high levels of dietary protein have been suspected to induce hypercalciuria. This increase has been found to be independent of the protein source. Intestinal calcium absorption appears to be increased by the high protein levels; serum calcium levels are not affected. Researchers have found varying effects on calcium balance; some have found that calcium balance is decreased, some have found no difference. Renal handling of calcium does appear to be altered; there is both a decreased renal tubular fractional reabsorption of calcium and an increased glomerular filtration rate. There are some data to suggest that these alterations may be due to the levels of sulfur-containing amino acids in diet. There are other data indicating that changing insulin levels may produce the hypercalciuria. Animal research suggests that there may be an increase in small intestine mucosal surface area.