Leucine Oxidation Research Articles

Effects of proteasome inhibitors MG132, ZL3VS and AdaAhx3L3VS on protein metabolism in septic rats

Proteasome inhibitors are novel therapeutic agents for the treatment of cancer and other severe disorders. One of the possible side effects is influencing the metabolism of proteins. The aim of our study was to evaluate the influence of three proteasome inhibitors MG132, ZL(3)VS and AdaAhx(3)L(3)VS on protein metabolism and leucine oxidation in incubated skeletal muscle of control and septic rats. Total proteolysis was determined according to the rates of tyrosine release into the medium during incubation. The rates of protein synthesis and leucine oxidation were measured in a medium containing L-[1-(14)C]leucine. Protein synthesis was determined as the amount of L-[1-(14)C]leucine incorporated into proteins, and leucine oxidation was evaluated according to the release of (14)CO(2) during incubation. Sepsis was induced in rats by means of caecal ligation and puncture. MG132 reduced proteolysis by more than 50% and protein synthesis by 10-20% in the muscles of healthy rats. In septic rats, proteasome inhibitors, except ZL(3)VS, decreased proteolysis in both soleus and extensor digitorum longus (EDL) muscles, although none of the inhibitors had any effect on protein synthesis. Leucine oxidation was increased by AdaAhx(3)L(3)VS in the septic EDL muscle and decreased by MG132 in intact EDL muscle. We conclude that MG132 and AdaAhx(3)L(3)VS reversed protein catabolism in septic rat muscles.

Postoperative Protein Sparing With Epidural Analgesia and Hypocaloric Dextrose

We examined the hypothesis that epidural analgesia prevents the increase in amino acid oxidation after elective colorectal surgery in patients receiving hypocaloric infusion of dextrose. Increased oxidative protein loss after surgery may adversely affect postoperative outcome. We have previously shown that effective segmental pain relief by epidural analgesia improves postoperative substrate utilization, resulting in less protein catabolism. We randomly allocated 10 patients to receive general anesthesia combined with epidural analgesia using bupivacaine/fentanyl and 10 to receive general anesthesia followed by patient-controlled analgesia with intravenous morphine. All patients received a peripheral 72-hour infusion of dextrose 10% from the day before until the second day after surgery. The dextrose infusion rate was adjusted to provide 50% of the patients' resting energy expenditure. The primary end point was whole-body leucine oxidation as determined by a stable isotope tracer technique (l-[1-C]leucine). In the intravenous analgesia group, leucine oxidation increased from 19 +/- 4 to 28 +/- 6 micromol kg h after surgery. Epidural analgesia prevented this increase of leucine oxidation (preoperative 21 +/- 6 micromol kg h, postoperative 21 +/- 5 micromol kg h). This difference was statistically significant (P = 0.01; analysis of variance for repeated measures). Perioperative epidural analgesia and hypocaloric dextrose infusion suppress the postoperative increase in amino acid oxidation, thereby saving more than 100 g of lean body mass per day.

Protein quantity, not protein quality, accelerates whole-body leucine kinetics and the acute-phase response during acute infection in marasmic Malawian children

The present study compared leucine kinetics and acute-phase-protein concentrations in three groups of marasmic, acutely infected Malawian children fed one of three isoenergetic diets. These were: an enhanced-protein-quality diet (egg-white+tryptophan, providing 1.2 g protein/kg per d; n 14); an increased-protein-content diet (egg-white+tryptophan, providing 1.8 g protein/kg per d; n 14); a standard-protein diet (1.2 g milk protein/kg per d; n 25). The hypotheses tested were that children receiving a diet with more protein would have greater rates of non-oxidative leucine disposal and that children receiving an isonitrogenous diet with a higher protein quality would have lower rates of leucine oxidation. The children were studied after 24 h of therapy using standard [(13)C]leucine stable-isotope tracer techniques. The children receiving the higher-protein-content diet had greater leucine kinetic rates than those receiving the standard-protein-content diet; non-oxidative leucine disposal was 170 (sd 52) v. 122 (sd 30) mumol leucine/kg per h (P<0.01). Leucine oxidation was less in the children receiving the enhanced-protein-quality diet than in those receiving the standard-protein-quality diet; 34 (sd 12) v. 45 (sd 13) mumol leucine/kg per h (P<0.05). The children receiving the high-protein-content diet increased their serum concentration for five of six acute-phase proteins 24 h after starting therapy, while those receiving the standard-protein-content diet did not. These data suggest that there was greater whole-body protein synthesis, and a more vigorous acute-phase response associated with the higher-protein-content diet. The clinical benefits associated with a higher protein intake in marasmic, acutely infected children need further study.

Protein metabolism in guanethidine-treated rats.

The aim of the present study was to evaluate the effect of short-term adrenergic blockade on the rate of whole-body protein turnover and leucine oxidation, and on protein synthesis in specific tissues in male rats. Adrenergic blockade was induced by guanethidine (100 mg/kg body weight subcutaneously). The control group was treated with saline. On the second day, the parameters of whole-body protein and leucine metabolism were evaluated using a primed constant intravenous infusion of L-[1-(14)C]leucine. Protein synthesis in tissues was determined on the basis of L-[1-(14)C]leucine incorporation. Guanethidine treatment caused a decrease in norepinephrine in skeletal muscle. Whole-body leucine oxidation and leucine oxidized fraction were higher in guanethidine-treated rats. There was an insignificant effect of guanethidine on whole-body proteolysis, protein synthesis and leucine clearance. However, protein balance was negative due to the larger difference between protein synthesis and proteolysis in guanethidine-treated animals compared to controls. In guanethidine-treated rats, protein synthesis was higher in the gastrocnemius muscle and in the kidneys and lower in liver and spleen. Changes in the small intestine and colon were insignificant. In addition, a marked decrease in concentration of several amino acids has been observed in the liver, the kidneys and the spleen. It is concluded that adrenergic blockade induced by guanethidine is associated with significant changes in protein metabolism, leucine oxidation and amino acid concentrations in several tissues. The most important consequences of treatment are considered to be a negative effect on protein balance, increased protein turnover in skeletal muscle and kidneys and decreased protein synthesis in the liver and spleen. These changes may also be induced by administration of other sympathetic blocking agents, e.g. in treatment of hypertension.

Daily requirement for total sulfur amino acids of chronically undernourished Indian men

Earlier studies of the requirement for total sulfur amino acids (SAAs; methionine in the absence of cystine) in healthy, well-nourished Indians indicated a value of 15 mg.kg(-1).d(-1), but it is unknown whether this estimate is applicable to chronically undernourished subjects. We assessed the total SAA requirement in otherwise clinically healthy, young, chronically undernourished adult Indians by using 7 test methionine intakes (3, 6, 9, 13, 18, 21, and 24 mg.kg(-1).d(-1)), without cystine, and by using both the 24-h indicator amino acid oxidation (24-h IAAO) and the 24-h indicator amino acid balance (24-h IAAB) methods. Twenty-one men were studied during each of 3 randomly assigned 7-d diet periods supplying methionine intakes (diet devoid of cystine) above and below the putative total 1985 FAO/WHO/UNU SAA requirement of 13 mg.kg(-1).d(-1). Twenty-four-hour IAAO and IAAB were measured on day 7 by use of a 24-h [(13)C]leucine tracer infusion. The breakpoint in the relation between these values and methionine intake was determined. Two-phase linear regression of daily leucine oxidation or the daily leucine balance against methionine intake estimated a breakpoint in the response curve at a methionine intake of 16 mg.kg(-1).d(-1) (95% Fiellers CI: 13, 22 mg.kg(-1).d(-1)). On the basis of the 24-h IAAO-IAAB approach, a mean total SAA requirement of 16 mg.kg(-1).d(-1) is proposed for undernourished Indian adults. This is not significantly different from that determined in Western and Indian well-nourished adults.

Whole-Body Leucine Kinetics and the Acute Phase Response during Acute Infection in Marasmic Malawian Children

This study compared leucine kinetics and acute-phase protein and cytokine concentrations in three groups of Malawian children who were fed an isoenergetic, isonitrogenous diet: children with marasmus with (n = 25) and without (n = 17) infection and well-nourished children with infection (n =13). The hypotheses tested were that whole-body leucine kinetics will be less in marasmic acutely infected children than in well-nourished acutely infected children but greater than in marasmic uninfected children. Children were studied after 24 h of therapy using standard (13)C-leucine stable isotope tracer techniques. Well-nourished children with acute infection had greater leucine kinetic rates than did marasmic children with acute infection; nonoxidative leucine disposal was 153 +/- 31 versus 118 +/- 43 micromol leucine. kg(-1). h(-1), leucine derived from whole-body proteolysis was 196 +/- 34 versus 121 +/- 47, and leucine oxidation was 85 +/- 31 versus 45 +/- 13 (p < 0.01 for all comparisons). Leucine kinetic rates were similar in marasmic children with and without acute infection. Well-nourished children with acute infection increased their serum concentration of five of six acute-phase proteins during the first 24 h, whereas marasmic children with infection did not have any increases. The serum concentrations of IL-6 were elevated in well-nourished and marasmic children with infection. These data suggest that the cytokine stimulus for the acute-phase protein kinetic response to acute infection is present in marasmic children but that the acute-phase protein metabolic response is blunted by malnutrition.

Short-term enteral glutamine does not enhance protein accretion in burned children: a stable isotope study

Objective Glutamine is a nonessential amino acid that, in recent years, has been found to play important roles in several metabolic and immunologic processes. It has been theorized that, in a stressed state, it may become “conditionally essential” because the patient's ability to manufacture glutamine may not be adequate to meet their needs under this condition. We chose to evaluate the ability of 48 hours of enteral glutamine to enhance immediate nitrogen accretion in stressed pediatric burn patients. Methods Nine children with serious burns who were tolerating tube feedings were enrolled in a human studies committee–approved protocol in which they received 48 hours of enteral feedings with glutamine replacing 20% of essential and nonessential amino acids and 48 hours of isonitrogenous, isocaloric standard enteral feedings. This interval was chosen to help ensure that the study periods were comparable from a metabolic perspective. At the end of each period, protein kinetics were determined by a primed constant infusion of L-[1- 13C] leucine tracer. The order of the studies was randomized. Seven children completed both phases of the study. Results were compared by paired t test and are presented as mean ± standard error of the mean. Results During the glutamine feeding period, the leucine flux and leucine oxidation rate were significantly lower than those in the conventional feeding period. This reflects a reduction in total leucine intake from 80 ± 11 to 62 ± 10 μmol/kg per hour. However, there was no significant difference in the net balance of leucine accretion into proteins between these 2 dietary periods, which indicated that enriched glutamine feeding for 48 hours did not result in an immediate whole body protein gain in this group of pediatric patients. In addition, plasma glutamine concentration showed a moderate increase after 48 hours of supplementation but did not reach significance. Conclusion Rapid protein accretion does not occur with short-term enteral glutamine supplementation. Several days of glutamine supplementation may be required to restore plasma glutamine levels and stimulate protein synthesis.

Kidney Protein Dynamics and Ammoniagenesis in Humans with Chronic Metabolic Acidosis

To evaluate the effects of chronic metabolic acidosis on protein dynamics and amino acid oxidation in the human kidney, a combination of organ isotopic ((14)C-leucine) and mass-balance techniques in 11 subjects with normal renal function undergoing venous catheterizations was used. Five of 11 studies were performed in the presence of metabolic acidosis. In subjects with normal acid-base balance, kidney protein degradation was 35% to 130% higher than protein synthesis, so net protein leucine balance was markedly negative. In acidemic subjects, kidney protein degradation was no different from protein synthesis and was significantly lower (P < 0.05) than in controls. Kidney leucine oxidation was similar in both groups. Urinary ammonia excretion and total ammonia production were 186% and 110% higher, respectively, and more of the ammonia that was produced was shifted into urine (82% versus 65% in acidemic subjects versus controls). In all studies, protein degradation and net protein balance across the kidney were inversely related to urinary ammonia excretion and to the partition of ammonia into urine, but not to total ammonia production, arterial pH, [HCO(-)(3)], urinary flow, the uptake of glutamine by the kidney, or the ammonia released into the renal veins. The data show that response of the human kidney to metabolic acidosis includes both changes in amino acid uptake and suppression of protein degradation. The latter effect, which is likely induced by the increase in ammonia excretion and partition into the urine, is potentially responsible for kidney hypertrophy.

Effect of Diet on Whole-Body Leucine Oxidation at Rest and During Prolonged Exercise and Recovery in Humans

Effect of Diet on Whole-Body Leucine Oxidation at Rest and During Prolonged Exercise and Recovery in Humans

Estrogen Supplementation Reduces Leucine Oxidation at Rest and During Moderate Intensity Endurance Exercise in Men

Estrogen Supplementation Reduces Leucine Oxidation at Rest and During Moderate Intensity Endurance Exercise in Men

Estrogen Supplementation Reduces Leucine Oxidation at Rest and During Moderate Intensity Endurance Exercise in Men

Estrogen Supplementation Reduces Leucine Oxidation at Rest and During Moderate Intensity Endurance Exercise in Men

Effect of Diet on Whole-Body Leucine Oxidation at Rest and During Prolonged Exercise and Recovery in Humans

Effect of Diet on Whole-Body Leucine Oxidation at Rest and During Prolonged Exercise and Recovery in Humans

The hyperinsulinemic amino acid clamp increases whole-body protein synthesis in young subjects

We propose that hyperinsulinemia stimulates protein synthesis when postabsorptive plasma amino acid (AA) concentrations are maintained. During a euglycemic hyperinsulinemic clamp, many AA, notably the branched-chain amino acids (BCAA), decline markedly. Therefore, we tested whether individual plasma AA could be maintained within the range of postabsorptive concentrations to assess the effects of insulin, infused at 40 mU/m 2 · min on whole-body protein and glucose metabolism, using [1- 13C]-leucine and [3- 3H]-glucose methodology. Validation studies of background [ 13C] enrichment and breath 13CO 2 recovery factors were performed in a subset of 6 subjects. In 10 healthy, young men, infusion rates of an AA solution were based on fluorometric determinations of total BCAA every 5 minutes. All 21 plasma AA remained in the target range; 15, including the BCAA, alanine, and glycine were within 13% of baseline, and only 6 (Thr, His, Arg, Asn, Cit, Tyr) varied more (18% to 42%). Notably, both leucine flux and nonoxidative leucine R d (protein synthesis) increased with insulin (2.36 ± 0.06 to 2.81 ± 0.10 and 1.79 ± 0.05 to 2.18 ± 0.10 μmol/kg fat-free mass (FFM) · min, respectively; P < .0005) while leucine oxidation only tended to increase ( P = .05) and endogenous leucine R a (protein breakdown) decreased by 18% (2.36 ± 0.06 to 1.94 ± 0.09 μmol/kg FFM · min; P < .0005), resulting in a marked elevation of net protein synthesis (−0.57 ± 0.02 to 0.24 ± 0.02 μmol/kg FFM · min; P < .0000001). Thus, in vivo protein anabolism was induced when maintaining postabsorptive plasma amino acid concentrations during hyperinsulinemia through a suppression of whole-body protein breakdown, no significant change in oxidation and an elevation of synthesis compared with postabsorptive conditions.

A Study of Substituent Effect on the Oxidative Strengths of N-Chloroarenesulphonamides: Kinetics of Oxidation of Leucine and Isoleucine in Aqueous Acid Medium

Abstract To study the variation of oxidative strengths of N-chloro-arenesulphonamides with substitution in the benzene ring, six mono- and five di-substituted N-chloro-arenesulphonamides are employed as oxidants for studying the kinetics of oxidation of two neutral amino acids, L-leucine and Lisoleucine in aqueous acid medium. The N-chloro-arenesulphonamides studied are of the constitution: ArSO2NaNCl·H2O (where Ar = C6H5, 4-CH3C6H4, 4-C2H5C6H4, 4-FC6H4, 4-ClC6H4, 4-BrC6H4, 2,3-(CH3)2C6H3, 2,4-(CH3)2C6H3, 2-CH3-4-ClC6H3, 2,4-Cl2C6H3, and 3,4-Cl2C6H3). The reactions show second order kinetics in [oxidant], fractional order in [amino acid] and inverse dependence on [H+]. Addition of the reduced product of the oxidants or variation in ionic strength of the medium has no significant effect on the rates of oxidations. A two-pathway mechanism is considered to explain the experimental results. Effective oxidizing species of the oxidants is Cl+ in different forms. Therefore the oxidising strengths of N-chloro-arenesulphonamides depend on the ease with which Cl+ is released from them. The study reveals that the introduction of substituent in the benzene ring of the oxidant affects both the kinetic and thermodynamic data for the oxidations The electron releasing groups such as CH3 generally inhibit the rates, while electron-withdrawing groups such as Cl enhance this ability, as the electron withdrawing groups ease the release of Cl+ from the reagents and hence increase the oxidising strengths. The on Ea and logA and validity of the Hammett and isokinetic relationships for the oxidations are also analysed.

Parenteral nutrition results in impaired lactose digestion and hexose absorption when enteral feeding is initiated in infant pigs

Preterm infants often receive total parenteral nutrition (TPN) before enteral feeding. Although TPN has been linked to mucosal atrophy, its effects on intestinal digestion, absorption, and metabolism are unknown. Our aim was to determine the effects of TPN on rates of intestinal nutrient absorption and metabolism in infant pigs after initiation of enteral feeding. Piglets were surgically implanted with catheters in the carotid artery, jugular vein, portal vein, and duodenum; an ultrasonic blood flow probe was inserted in the portal vein. Piglets were given TPN (TPN group) or enterally fed formula (enteral group) for 6 d. On day 7, both groups were enterally fed a milk-based formula, and the net portal absorption and metabolism of enteral [(2)H]glucose and [(13)C]leucine were measured. After enteral feeding began, portal blood flow increased by 27% and 41% above the basal rate in the enteral and TPN groups, respectively; oxygen consumption remained lower in the TPN group. During enteral feeding, the net portal absorption of glucose was lower in the TPN group and that of galactose was not significantly different between the groups; lactate release was higher in the TPN group. Portal absorption accounted for only approximately 37% of galactose intake in both groups. The TPN group had lower net portal absorption of arginine, lysine, threonine, and glycine. The portal absorption of dietary leucine was not significantly different between the groups; the arterial utilization and oxidation of leucine were significantly lower in the TPN group. Short-term TPN results in decreased lactose digestion and hexose absorption and increased intestinal utilization of key essential amino acids when enteral feeding is initiated in piglets.

Acute effects of decreased glutamine supply on protein and amino acid metabolism in hepatic tissue: a study using isolated perfused rat liver

Glutamine deficiency, a common finding in severe illness, has a negative influence on immune status, protein metabolism, and disease outcome. In several studies, a close relationship between glutamine, branched-chain amino acid (BCAA), and protein metabolism was demonstrated. The aim of the present study was to investigate the effect of glutamine deficiency on amino acid and protein metabolism in hepatic tissue using a model of isolated perfused rat liver (IPRL). Parameters of protein metabolism and amino acid metabolism were measured using both recirculation and single pass technique with L-[1- 14C]leucine and [1- 14C]ketoisocaproate (KIC) as a tracer. Glutamine concentration in perfusion solution was 0.5 mmol/L in control and 0 mmol/L in the glutamine-deficient group. The net release of glutamine (about 11 μmol/g/h) and higher net uptake of most of the amino acids was observed in the glutamine-deficient group. There was an insignificant effect of lack of glutamine on hepatic protein synthesis, proteolysis, and the release of urea. However, significantly lower release of proteins by the liver perfused with glutamine-deficient solution was observed. The lack of glutamine in perfusion solution caused a significant decrease in leucine oxidation (6.66 ± 1.04 v 13.67 ± 2.38, μmol/g dry liver/h, P < .05) and an increase in KIC oxidation (163.7 ± 16.5 v 92.0 ± 12.9 μmL/g dry liver/h, P < .05). We conclude that decreased delivery of glutamine to hepatic tissue activates glutamine synthesis, decreases resynthesis of essential BCAA from branched-chain keto acids (BCKA), increases catabolism of BCKA, and has an insignificant effect on protein turnover in hepatic tissue.

The protein metabolic response to HIV infection in young children

Growth failure often precedes secondary infections in HIV-infected infants and children, suggesting that inadequate protein deposition may be an early manifestation of infection by the virus. However, the protein metabolic response elicited by the virus in young children is unknown. We compared children with HIV infection and age-matched children without HIV infection with regard to whole-body and splanchnic protein kinetics and synthesis of acute phase proteins (APPs). Whole-body and splanchnic leucine kinetics and fractional and absolute synthesis rates of 2 positive and 4 negative APPs were measured in 6 asymptomatic, HIV-infected children (4 males and 2 females) aged 6-17 mo and 4 uninfected children (3 females and 1 male) aged 7-9 mo who were in the fed state. Compared with the control children, the HIV-infected children had significantly lower dietary energy and protein intakes and leucine balance and significantly faster leucine flux and fractional splanchnic leucine extraction; there was no significant difference between the groups in leucine oxidation rates. The HIV-infected children also had significantly higher plasma concentrations and absolute synthesis rates of the positive APPs and a significantly higher fractional synthesis rate of fibrinogen. The concentrations of 2 of the 4 negative APPs, albumin and HDL apolipoprotein A-I, were significantly lower in the HIV-infected children but were not associated with slower synthesis rates. Children with HIV infection but without secondary infection have reduced protein balance because of an inability to down-regulate protein catabolism. Furthermore, the acute phase protein response elicited by HIV infection is characterized by higher concentrations and synthesis rates of positive APPs without lower concentrations of some negative APPs.

Potential role of leucine metabolism in the leucine-signaling pathway involving mTOR.

Leucine has been shown to stimulate adipose tissue protein synthesis in vivo as well as leptin secretion, protein synthesis, hyper-plastic growth, and tissue morphogenesis in in vitro experiments using freshly isolated adipocytes. Recently, others have proposed that leucine oxidation in the mitochondria may be required to activate the mammalian target of rapamycin (mTOR), the cytosolic Ser/Thr protein kinase that appears to mediate some of these effects. The first irreversible and rate-limiting step in leucine oxidation is catalyzed by the branched-chain alpha-keto acid dehydrogenase (BCKD) complex. The activity of this complex is regulated acutely by phosphorylation of the E1alpha-subunit at Ser293 (S293), which inactivates the complex. Because the alpha-keto acid of leucine regulates the activity of BCKD kinase, it has been suggested as a potential target for leucine regulation of mTOR. To study the regulation of BCKD phosphorylation and its potential link to mTOR activation, a phosphopeptide-specific antibody recognizing this site was developed and characterized. Phospho-S293 (pS293) immunoreactivity in liver corresponded closely to diet-induced changes in BCKD activity state. Immunoreactivity was also increased in TREMK-4 cells after the induction of BCKD kinase by a drug-inducible promoter. BCKD S293 phosphorylations in adipose tissue and gastrocnemius (which is mostly inactive in vivo) were similar. This suggests that BCKD complex in epididymal adipose tissue from food-deprived rats is mostly inactive (unable to oxidize leucine), as is the case in muscle. To begin to test the leucine oxidation hypothesis of mTOR activation, the dose-dependent effects of orally administered leucine on acute activation of S6K1 (an mTOR substrate) and BCKD were compared using the pS293 antibodies. Increasing doses of leucine directly correlated with increases in plasma leucine concentration. Phosphorylation of S6K1 (Thr389, the phosphorylation site leading to activation) in adipose tissue was maximal at a dose of leucine that increased plasma leucine approximately threefold. Changes in BCKD phosphorylation state required higher plasma leucine concentrations. The results seem more consistent with a role for BCKD and BCKD kinase in the activation of leucine metabolism/oxidation than in the activation of the leucine signal to mTOR.

Gender differences in the regulation of amino acid metabolism.

Exercising men, compared with women, have a greater increase in leucine oxidation but not lysine rate of appearance. The cause for this sexual dimorphism is unknown; however, an inhibition of beta-adrenoreceptor activity has previously been shown to mediate amino acid metabolism (Lamont LS, McCullough AJ, and Kalhan SC. Am J Physiol Endocrinol Metab 268: E910-E916, 1995; Lamont LS, Patel DG, and Kalhan SC. J Appl Physiol 67: 221-225, 1989). This study was a gender comparison of leucine and lysine kinetics during a beta-adrenoreceptor blockade (beta1,beta2-blockade) and a placebo control by using a double-blind crossover protocol. Subjects exercised at 50% of their trial-specific maximal O2 consumption (1 h) after 7 days of dietary control. During exercise with beta-blockade, men had an increased nonprotein respiratory exchange ratio (P < 0.001), whereas women had an increased circulation of free fatty acids (P < 0.001). The genders also displayed distinct differences in exercise amino acid kinetics. The men, but not the women, increased leucine oxidation (P < 0.005) and lysine rate of appearance (P < 0.009) when exercising during beta-adrenergic blockade. This study indicates that during beta-blockade, exercising men increase their need for amino acids (and carbohydrate) to fuel energy needs, whereas women increase their mobilization of fat, thereby requiring less alternative fuels such as carbohydrate and amino acids. Gender-specific fuel preferences during exercise are regulated by beta-adrenergic-receptor activity. Substrate availability during exercise appears to modulate the amino acid oxidation differences between genders.

Effect of acute acidosis on protein and amino acid metabolism in rats

Background & aims: Metabolic acidosis is a common finding in critical illness. The aim of the present study was to evaluate acute acidosis as a signal that induces changes in protein metabolism. Methods: In the first study, Wistar rats were infused for 6 h with HCl or saline resulting in blood pH 7.30±0.03 and 7.46±0.02, respectively. The whole body protein metabolism was evaluated using l-[1- 14C]leucine. In the second study, soleus and extensor digitorum longus muscles from normal rats were incubated in medium, pH 7.4, 7.3 or 7.0. Protein metabolism was evaluated using l-[1- 14C]leucine and tyrosine release. Results: In the in vivo study we observed increased protein turnover–protein synthesis, proteolysis and leucine oxidation and more negative protein balance in rats with acidosis. There was no change in protein synthesis in gastrocnemius muscle. We observed an increase in plasma levels of most amino acids including branched-chain amino acids and a decrease in intracellular amino acid pool in skeletal muscle. In vitro decrease in pH of 0.1 had no effect on protein metabolism, decrease of 0.4 decreased protein turnover and leucine oxidation. Conclusion: Acute metabolic acidosis is a protein wasting condition. Direct effect of acidosis on skeletal muscle is under condition in vivo modified by neurohumoral regulations.