Amino Acid Kinetics Research Articles

Whole-body valine and cysteine kinetics and tissue fractional protein synthesis rates in lambs fed Sulla (<I>Hedysarum coronarium</I>) and infected or not infected with adult <I>Trichostrongylus colubriformis</I>

Poor growth during parasitic infection may be due to a redistribution of amino acids away from skeletal muscle protein synthesis to the intestinal site of infection. The effect of a Trichostrongylus colubriformis infection on whole-body amino acid kinetics and tissue fractional protein synthesis rates were determined in lambs fed fresh Sulla (Hedysarum coronarium; 800 g DM/d). Lambs were dosed with 6000 L3 Trichostrongylus colubriformis larvae daily for 6 d (n 6) or kept as parasite-free controls (n 6). On day 45 post-infection, the lambs received an intravenous injection of 2H2O and infusions (8 h) of [35S]sulphate to measure the size of the whole-body water and sulphate pools, respectively. On day 48, the lambs were continuously infused for 8 h with [3,4-3H]valine into the jugular vein as well as with [1-13C]valine and [35S]cysteine into the abomasum. After the 8 h infusions, the lambs were killed and tissue samples collected from the duodenum, ileum, mesenteric lymph nodes, liver, spleen, thymus, muscle and skin. Feed intake (769 v. 689 (sd 47) g DM/d) was not affected by infection, whereas liveweight gains (50 v. -50 (sd 70) g/d) were lower and intestinal worm burdens (240 v. 18,000 (sd 7000) worms) higher in the infected lambs. Parasitic infection increased the fractional protein synthesis rates in the small intestine, mesenteric lymph nodes and liver but did not affect skin and skeletal muscle fractional protein synthesis rates during the established parasitic infection.

Effect of insulin on human skeletal muscle protein synthesis is modulated by insulin-induced changes in muscle blood flow and amino acid availability

Insulin promotes muscle anabolism, but it is still unclear whether it stimulates muscle protein synthesis in humans. We hypothesized that insulin can increase muscle protein synthesis only if it increases muscle amino acid availability. We measured muscle protein and amino acid metabolism using stable-isotope methodologies in 19 young healthy subjects at baseline and during insulin infusion in one leg at low (LD, 0.05), intermediate (ID, 0.15), or high (HD, 0.30 mUxmin(-1)x100 ml(-1)) doses. Insulin was infused locally to induce muscle hyperinsulinemia within the physiological range while minimizing the systemic effects. Protein and amino acid kinetics across the leg were assessed using stable isotopes and muscle biopsies. The LD did not affect phenylalanine delivery to the muscle (-9 +/- 18% change over baseline), muscle protein synthesis (16 +/- 26%), breakdown, or net balance. The ID increased (P < 0.05) phenylalanine delivery (+63 +/- 38%), muscle protein synthesis (+157 +/- 54%), and net protein balance, with no change in breakdown. The HD did not change phenylalanine delivery (+12 +/- 11%) or muscle protein synthesis (+9 +/- 19%), and reduced muscle protein breakdown (-17 +/- 15%), thus improving net muscle protein balance but to a lesser degree than the ID. Changes in muscle protein synthesis were strongly associated with changes in muscle blood flow and phenylalanine delivery and availability. In conclusion, physiological hyperinsulinemia promotes muscle protein synthesis as long as it concomitantly increases muscle blood flow, amino acid delivery and availability.

Carbonation monitoring of beverage in a laboratory scale unit with on-line measurement of dissolved CO 2

The effervescence properties of carbonated drinks are subject to the concentration of carbon dioxide dissolved and its ability to be transferred from the liquid phase to the forming bubble. We report the construction of a small laboratory scale carbonation unit that allows the study of the solubility of carbon dioxide in various hydro-alcoholic media, differing in their compositions. This unit, which is a model of a real industrial one, measures the instant concentration of CO 2, during the carbonation process, by means of a thermal conductivity detector. The carbonation kinetics of various samples, containing water, alcohol, sugar, proteins and free amino-acids, were studied. While sugar diminishes CO 2 solubility and, consequently, carbonation kinetics, free amino-acids and proteins increase the concentration of carbon dioxide in the medium. A survey of the rheological properties of the samples showed that CO 2 solubility modifications are not correlated with changes in the viscosity of the medium. This equipment could be helpful for soft drink bottlers for measuring the changes that may affect effervescence and consequently the visual and gustative perception of the beverage after modification of its composition.

An investigation of the pyrolysis kinetics of some aliphatic amino acids

The thermal behavior of some aliphatic amino acids, including alanine, valine, leucine, isoleucine, and proline was investigated by thermogravimetry (TG) in the range of temperatures within 30–400 °C. Pyrolysis of these amino acids was performed at various heating rates under inert (non-oxidative) conditions. The kinetic analysis was carried out using a composite procedure involving the iso-conversional method and the master plots method. The iso-conversional method indicated that the pyrolysis reaction should conform to single reaction model. The master plots method suggested that the phase boundary reaction models best describe the pyrolysis of alanine, valine, leucine and isoleucine, while the pyrolysis of proline should conform to the simple order reaction model. Also, for each amino acid, the kinetic parameters, such as activation energy and pre-exponential factor, were determined, respectively.

In vitro Determination of the Release Kinetics of Peptides and Free Amino Acids During the Digestion of Food Proteins

The kinetics of peptide release during in vitro digestion of 4 protein sources (casein, cod protein, soy protein, and gluten) were investigated. Samples were sequentially hydrolyzed with pepsin (30 min) and pancreatin (2, 4, or 6 h) in a dialysis cell with continuous removal of digestion products. Nondialyzed digests were fractionated by ion-exchange chromatography and ultrafiltration. Animal proteins were digested at a greater rate than plant proteins. Target amino acids of specific enzymes appeared more rapidly in the dialyzed fractions when compared to other amino acids. Throughout the hydrolysis, nondialyzed digests contained a higher proportion of peptide mixtures with basic-neutral properties. Except for gluten, peptide fractions with molecular weights that exceeded 10 kDa (basic-neutral, BN > 10) were rapidly hydrolyzed during the first 2 h of pancreatin digestion. The kinetics of release and the composition of peptide fractions were different when the protein sources were compared. The analysis of amino acids revealed that threonine and proline proportions were relatively high in BN > 10 and in peptide fractions with molecular weight between 10-1 kDa (BN 10-1), while tyrosine, phenylalanine, lysine, and arginine predominated in the low molecular weight (<1 kDa) fractions. More resistant peptides were generally rich in proline and glutamic acid. The role of in vitro digestion assays in dietary protein quality evaluation is discussed.

Does Hemodialysis Increase Protein Breakdown? Dissociation between Whole-Body Amino Acid Turnover and Regional Muscle Kinetics

Hemodialysis (HD) is a protein catabolic procedure. Whole-body amino acid turnover studies identify dialysate amino acid loss and reduced protein synthesis as the catabolic events; proteolysis is not increased. Regional amino acid kinetics, however, document enhanced muscle protein breakdown as the cause of the catabolism; muscle protein synthesis also increased but to a lesser magnitude than the increment in protein breakdown. This discordance between whole-body and regional kinetics is best explained by the contrasting physiology between the muscle and the liver. During HD, muscle releases amino acids, which then are taken up by the liver for de novo protein synthesis. There seems to be a somatic to visceral recycling of amino acids. Evidence supporting this concept includes the increased fractional synthesis of albumin and fibrinogen during HD. It should be emphasized that region- or organ-specific kinetics vary, and whole-body turnover is a composite of all of the visceral and somatic compartments taken together. Reduced whole-body protein synthesis may be a compensatory adaptation to dialysate amino acid loss with a consequent reduction in plasma amino acid concentration. Notwithstanding the protein catabolic nature of HD, evidence is accumulating that intradialytic nutritional supplementation may blunt its catabolic effect.

Microdialysis to investigate tissue amino acid kinetics

This review discusses recent developments in the utilization of microdialysis to assess tissue amino acid kinetics. Three questions regarding the use of microdialysis to assess amino acid kinetics have recently been addressed. Does glutamate measured in the interstitial fluid of the brain represent neurotransmission activity? Can local nitric oxide production be determined with the use of microdialysis? Finally, how can skeletal muscle amino acid metabolism be studied in more detail utilizing microdialysis? The most appropriate way to assess tissue kinetics is by the use of tracers. The number of studies actually utilizing microdialysis in combination with tracers to assess amino acid kinetics is rather limited. However, these studies show exiting new insides into in-vivo amino acid kinetics.

Amino acid control of muscle protein turnover in renal disease

This review discusses the concept that skeletal muscle intracellular amino acids (ICAAs), in particular the essential amino acids, are regulated throughout a wide range of physiologic circumstances. Whether in critical illness, severe injury, or healthy states, ICAAs are closely regulated by a coordinated response in 1 or more of the processes of synthesis, breakdown, and tissue transport. For a given metabolic signal (hormonal, change in plasma amino acid concentrations), the regulation of ICAAs entails appropriate and corresponding changes in amino acid kinetics. These changes vary according to the strength of the metabolic signal and the existing requirement to maintain the ICAA pool. For the patient with end-stage renal disease (ESRD), frequent dialysis induces an abrupt removal of half of the circulating amino acids, which in turn results in a substantial efflux of amino acids from skeletal muscle. ICAAs are maintained through the increase in protein breakdown, and similar to other stress states, there is a concomitant increase in protein synthesis. Thus, the regulation of ICAAs often pushes subsequent adaptations in amino acid kinetics to maintain the existing homeostasis. This regulatory mechanism is evident in circumstances ranging from increased amino acid availability in healthy volunteers to a change in anabolic signal in severe injury. Despite the substantial evidence of ICAA regulation, its physiologic significance is not evident. However, the regulation of ICAAs represents a method by which skeletal muscle ensures its capacity for anabolism.

Supplementation with Aromatic Amino Acids Improves Leucine Kinetics but Not Aromatic Amino Acid Kinetics in Infants with Infection, Severe Malnutrition, and Edema

We investigated whether supplementation with an aromatic amino acid (AAA) cocktail consisting of 0.5 mmol each of phenylalanine, tryptophan, and tyrosine compared with isonitrogenous amounts of alanine (Ala) would improve measures of protein kinetics in 14 (8 with AAA, 6 Ala) children with edematous malnutrition (aged 6-24 mo) during the infected acute malnourished state. Supplementation started immediately after the baseline experiment, 2 d postadmission and continued to the end of the acute phase of treatment. The second (postsupplementation) experiment was done approximately 12 d postadmission. We measured leucine kinetics, phenylalanine and tyrosine fluxes, using an i.g. 8-h prime continuous infusion of (2)H(3)-leucine, and an i.v. 6-h prime continuous infusion of (13)C-leucine, (2)H(2)-tyrosine, and (2)H(5)-phenylalanine in the fed state. Leucine flux tended to be faster (P = 0.06) in the AAA group compared with Ala group after supplementation (mean difference +/- SEM): 22.6 +/- 10.9 micromol/(kg . h). The rate of leucine appearance from protein breakdown [28.1 +/- 9.4 micromol/(kg . h)] and the nonoxidative disposal of leucine [i.e., leucine to protein synthesis; 35.4 +/- 12.9 micromol/(kg . h)] were faster (P < 0.02) in the AAA group than in the Ala group. There was no significant effect of supplementation on leucine splanchnic metabolism, phenylalanine, and tyrosine fluxes. These findings are consistent with the hypothesis that the blunting of the protein catabolic response to infection in children with edematous malnutrition syndrome is due to limited availability of aromatic amino acids.

Maternal-fetal transport kinetics of L-Leucine in vitro in gestational diabetic pregnancies

Paucity of data relating to transport of amino acids in gestational diabetic pregnancies prompted us to undertake this study. Transport kinetics of a model amino acid, L-leucine was investigated in gestational diabetic pregnancies in vitro, using perfusion of isolated placental lobules. Placentae from diabetic and control pregnant women were collected post-partum. Suitable placental lobules were then perfused, using National Culture and Tissue Collection (NCTC) medium, diluted with Earle's buffered salt solution as perfusate. 14C-labelled L-leucine along with tritiated water as reference were injected as a 100 ul bolus into the maternal circulation and serial perfusate samples collected over a 5-minute study period. In 6 successful perfusions, differential transport rate of L-leucine for 10, 25, 50, 75 and 90% of efflux in the fetal vein averaged 1.17, 1.12, 1.22, 1.20 and 1.17 times respectively that of reference in the diabetic group. In the control group (n=6), leucine transport indices for the corresponding efflux periods averaged 1.13, 1.15, 1.18, 1.17 and 1.16 times respectively that of the reference marker. Student's 't' test showed that the difference between the two groups was not statistically significant (p > 0.05) for all the efflux fractions studied. In the diabetic series, leucine transport fraction (TF) averaged 41.2 +/- 4.5% of corresponding water TF while in control group, the amino acid TF averaged 46.5 +/- 6.5% of water TF. The difference between the two series, however was not statistically significant (p > 0.05). Similarly, kinetic parameters as area under the curve, clearance, elimination constant, time for maximum response, absorption rate, and elimination rate in the diabetic and control groups, were not significantly different (p > 0.05) as well. Our study seems to indicate that transport kinetics of leucine under in vitro conditions, do not differ significantly in placentae of gestational diabetic women compared to controls.

Study on the transport selectivity and kinetics of amino acids through di(2-ethylhexyl) phosphoric acid-kerosene bulk liquid membrane

Transport selectivity and kinetics of amino acids through di(2-ethylhexyl) phosphoric acid-kerosene bulk liquid membrane have been studied. The liquid-membrane system exhibited excellent transport selectivity for amino acids containing a side chain of high lipophilicity constant, like l-phenylalanine, l-tryptophan, l-leucine, and l-isoleucine. Main factors affecting the amino acids transport have been discussed. As a target amino acid with bulky aromatic side-chain of l-phenylalanine, the influence of its concentration and the concentration of di(2-ethylhexyl) phosphoric acid on the interfacial tension, and the effect of temperature on its transport through the bulk liquid membrane were investigated. The transport kinetics of l-phenylalanine could be analyzed in the formalism of a reversible pseudo-first-order reaction followed by an irreversible pseudo-first-order reaction. The pseudo-first-order apparent rate constants of the interfacial transport of l-phenylalanine for the extraction reaction, extraction back reaction, and stripping reaction were estimated.

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.

Postprandial Kinetics of Dietary Amino Acids Are the Main Determinant of Their Metabolism after Soy or Milk Protein Ingestion in Humans

Soy proteins have been shown to result in lower postprandial nitrogen retention than milk proteins, but the mechanisms underlying these differences have not been elucidated. To investigate this question, we measured the postprandial kinetics of the appearance of individual (15)N-amino acids in the serum of healthy adults after the ingestion of either (15)N-soy (n = 8) or (15)N-milk proteins (n = 8) in a mixed single meal (46 kJ/kg). The kinetics of total and dietary amino acids (AA) in the peripheral circulation were characterized by an earlier and higher peak after soy protein ingestion. Dietary AA levels peaked at 2.5 h in the soy group vs. 3.9 h in the milk group (P < 0.02). This time interval difference between groups was associated with a faster transfer of dietary N into urea in the soy group (peak at 3 vs. 4.75 h in the milk group, P < 0.005) and a higher level of incorporation into the serum protein pool from 3 to 8 h after the soy meal. The dietary AA pattern in the peripheral blood closely reflected the dietary protein AA pattern. Postprandial glucose, insulin, and glucagon levels and profiles did not differ between groups. Soy AA were digested more rapidly and were directed toward both deamination pathways and liver protein synthesis more than milk AA. We conclude that differences in the metabolic postprandial fates of soy and milk proteins are due mainly to differences in digestion kinetics; however, the AA composition of dietary proteins may also play a role.

Free amino acid pool and muscle protein balance after resistance exercise.

The aim of this study was to assess the effects of a resistance exercise session (RES) on free amino acid concentrations and protein synthesis and breakdown of the vastus lateralis (VL) muscle during recovery in male subjects. Both the exercise group (EG) and the control group (CG) consisted of six healthy physically active men. On the experiment day in fasting conditions, a stable isotopic tracer of L-[ring-2H(5)] phenylalanine was infused and EG started a heavy 50-min hypertrophic RES for lower extremities after 55 min of infusion. At the same time, CG was at rest. During recovery of 195 min after RES, several blood samples were drawn from the femoral artery (FA) and the femoral vein (FV) and muscle samples from the VL muscle. The enrichment was analyzed by GC/MS and leg muscle amino acid kinetics determined by three-pool compartment model between FA, FV, and VL. During recovery at 60 min after RES, there was no difference in muscle protein synthesis or muscle protein breakdown between the groups, but at 195 min, both muscle protein synthesis (P < 0.05) and muscle protein breakdown (P < 0.05) were increased in EG compared with CG. The protein net balance was negative and similar in both groups. Simultaneously in serum concentrations, there was a decrease in leucine (P < 0.05) associated with an increase in aspartate (P < 0.05). Furthermore, the exercise-induced increase in alanine concentration decreased both in serum and muscle. In fasting conditions, protein net balance is negative and RES induces an increase in muscle protein synthesis and breakdown at 195 min but not yet at 60 min of recovery.

Minimum Protein Intake for the Preterm Neonate Determined by Protein and Amino Acid Kinetics

Minimum Protein Intake for the Preterm Neonate Determined by Protein and Amino Acid Kinetics

Minimum protein intake for the preterm neonate determined by protein and amino acid kinetics.

Lower limits of protein needs in prematurely born neonates have not been adequately studied, yet providing protein in amounts maximizing accretion without excess is a goal in these infants' nutritional care. We hypothesized that with the use of amino acid oxidation methodology, it would be possible to define minimum protein requirement. Our objective was to investigate protein kinetics during short-term changes in protein intake by measurement of nitrogen balance and amino acid flux and oxidation using [(15)N]glycine, [(13)C]phenylalanine, and [(13)C]leucine tracers. Protein kinetics were examined in 21 preterm infants (gestational age: 29 +/- 3 wk; birth weight: 1091 +/- 324 g) at five protein intakes (1.0, 1.5, 2.0, 2.5, and 3.0 g x kg(-1) x d(-1)) with 1 d of adaptation to the test intakes. From nitrogen balance data, a protein need of 0.74 g x kg(-1 x -1) was estimated to achieve zero balance. For all three amino acids, flux and oxidation estimates were not different across protein intakes. Whole-body protein synthesis and breakdown estimates from [(15)N]ammonia data were 14.6 +/- 3.4 and 14.4 +/- 4.1 g x kg(-1) x d(-1), respectively. Glycine flux (680 +/- 168 micromol x kg(-1) x h(-1)) was greater than leucine flux (323 +/- 115 micromol x kg(-1) x h(-1)), which was greater than phenylalanine flux (84.3 +/- 35.2 micromol x kg(-1) x h(-1)). Leucine oxidation (36.7 +/- 15.6 micromol x kg(-1) x h(-1)) was also greater than phenylalanine oxidation (6.64 +/- 4.41 micromol x kg(-1) x h(-1)). Infants in our study were able to adapt to short-term changes in protein intake with little consequence to the overall whole-body protein economy, as measured by the three test amino acids.

Protein and Amino Acid Metabolism in the Fetal-Placental Unit

After completing this article, readers should be able to: 1. Determine the rate of fetal nitrogen accretion and compare it with the fetal growth rate. 2. Characterize fetal urea production on a weight-specific basis. 3. Explain the effects of hypoglycemia on the fetus. 4. Explain the effects of intrauterine growth retardation on the fetal amino acid profile. Protein synthesis and accretion are the cornerstones of growth that provide the structural framework and enzymatic machinery necessary for fetal development. The maternal uterine circulation supplies the components that the fetus uses for protein accretion. All are derived from the maternal diet or maternal tissue stores. It is important to explore the regulatory processes within the maternal, placental, and fetal compartments that determine fetal amino acid retention. In addition to tissue synthesis, use of free amino acids as oxidative fuel is extensive in the well-nourished fetus and increases significantly during periods of maternal food deprivation. The changes in fetal amino acid utilization represent a significant mechanism by which the fetus adapts to energy deprivation. Before examining the available data, it is necessary to understand the models and methodology by which the data are derived. In general, four methods have been applied to fetal nitrogen metabolism: 1) carcass analysis, 2) net umbilical uptake determinations, 3) measurement of the rate of incorporation of a tracer amino acid into fetal protein, and 4) studies of the kinetics of amino acids in the fetal arterial free amino acid pool. Many studies have combined aspects of two or more of the these methods. ### Carcass Analysis For this method, individual fetuses are sacrificed at several points during gestation, and chemical analysis is performed on the carcass. The total amount of nitrogen, amino acid, or protein at that point in gestation can be determined. Data from individual fetuses are pooled to obtain an accretion curve. This …

Amino acid kinetics during the anhepatic phase of liver transplantation.

Alanine and glutamine are interorgan nitrogen/carbon carriers for ureagenesis and gluconeogenesis, which are mainly but not necessarily only hepatic. The liver is central to alanine and glutamine metabolism, but most organs can produce and use them. We studied amino acid kinetics after liver removal to depict initial events of liver failure and to provide a model to study extrahepatic gluconeogenesis and nitrogen disposal in humans. We measured amino acid kinetics with [5,5,5-(2)H(3)]leucine and [3-(13)C]alanine or [1,2-(13)C(2)]glutamine tracers in 21 subjects during and after the anhepatic phase of liver transplantation: 12 were at 7 months posttransplantation, and 7 were healthy control subjects. Anhepatic leucine kinetics, including proteolysis, was unchanged. Alanine plasma and whole-body contents increased 3x and 2x, with a halved metabolic clearance and a doubled production, 2% greater than disposal. Free whole-body glutamine decreased 25% but increased 50% in plasma. Glutamine clearance was halved, and the production decreased by 25%, still 2% greater than disposal. Liver replacement decreased alanine and glutamine concentrations, leaving leucine unchanged. Liver removal caused doubled alanine fluxes, minor changes in glutamine, and no changes in leucine. The initial events after liver removal are an accumulation of three-carbon compounds, an acceleration of alanine turnover, and limited nitrogen storage in alanine and glutamine.

Effect of increased glucose load on maternal-fetal transport of alpha-aminoisobutyric acid in the perfused human placenta: in vitro study.

The role of hyperglycemia on modulation of maternal-fetal transport of amino acids in humans is little understood. Hence, we have explored the effect of increased glucose load on transport kinetics of a model non-metabolizable amino acid, alpha-aminoisobutyric acid (AIB), in the human placenta in vitro. Transport kinetics of AIB in maternal-fetal direction was studied using perfusion of isolated human placental lobules. NCTC (National Culture and Tissue Collection)-135 medium, diluted with Earle's buffered salt solution was used as the perfusate and tritiated water was used as the reference marker. Effect of increased glucose load on transport kinetics of study and reference substances was studied in normal term placentae (n=5; gestational age, 38.5 +/- 0.5 weeks) in succeeding experimental phases, after a control perfusion phase with physiological glucose concentration. AIB transport fraction (TF), relative to tritiated water TF, averaged 54.8% in control euglycemic phase while in hyperglycemic concentration phases of 27.8 and 55.6 mM, the AIB TF index averaged 42.4% and 38.2%, respectively. Analysis of variance revealed that the difference was statistically significant. Similarly, absorption rate index of the amino acid was also significantly lower in the hyperglycemic perfusion phases compared to control euglycemic phase. We conclude that hyperglycemia may play a deleterious role in limiting maternal-fetal transport of A-type amino acids in the in vivo state.

WHOLE BODY PROTEIN METABOLISM IS REDUCED WITH AGING BUT IS UNAFFECTED BY AEROBIC EXERCISE TRAINING

Conflicting previous reports on the effect of age on whole body protein metabolism may be related to small sample sizes, changes in body composition, or diet and exercise status. The effect of aerobic exercise training on whole body protein turnover remains to be determined. PURPOSE: This study tested the hypothesis that aging is associated with a reduction in whole body protein turnover that may be reversed by an aercbic exercise training program. METHODS: Healthy, previously untrained subjects (N = 78, age 21–88 y) were studied before and after four months of bicycle training (ExTr, up to 45 min at 80% HRmax, 3–4d/week) or control activity using [13C] leucine (Leu) and [15N] phenylalanine (Phe) tracers. Diet and activity were standardized for 3 days prior to each study. RESULTS: Aging was associated with declines in Phe (r = 0.68) and Leu (r = 0.66) flux, Leu oxidation (r = 0.68) and non-oxidative Leu disposal (r = 0.58) in both men and women, all p < 0.01. The decreases were 4–5% per decade, regardless of whether the data were expressed as μmol/h or normalized for body mass or fat-free mass (FFM, from dual x-ray absorptiometry). FFM, which also declined 3% per decade, was the best correlate of Leu (r = 0.88) and Phe (r = 0.78) fluxes, but did not eliminate the significant contribution of age in multiple regression models. Control subjects had no change in VO2max, FFM or amino acid kinetics and the coefficients of variation for these measurements were ≤ 5.3%. ExTr imporved VO2max 10 ± 1% (p < 0.01) in all subjects, regardless of age, but did not alter FFM or amino acid kinetics. CONCLUSION: This study demonstrates that aging is associated with reduced rates of whole body protein turnover that are not corrected by four months of aerobic training. This may represent an irreversible age-related decrease in tissue remodeling. Support: NIH RO1AG09531, MO1RR00585