Search PubMed⌕ Search

Biomedical subjects

V R Young

Publications and source records attributed to V R Young.

At least 73 records · Page 4Linked to original sources
PubMed1996

Diurnal pattern of the interrelationships among leucine oxidation, urea production, and hydrolysis in humans.

We investigated in six healthy adult men, who received an adequate intake of protein (1 g.kg-1.day-1), the relationship among urea production, excretion, and hydrolysis. At the end of a 6-day diet-adjustment period, subjects were studied using a 24-h continuous intravenous [1-13C]leucine and [15N,15N]urea tracer protocol (A. E. El-Khoury, N. K. Fukagawa, M. Sánchez, R. H. Tsay, R. E. Gleason, T. E. Chapman, and V. R. Young. Am. J. Clin. Nutr. 59: 1000-1011, 1994) to determine rates of irreversible protein nitrogen loss and urea kinetics. By combining leucine and urea kinetic data, we found a significant degree of urea hydrolysis over the 24-h period but no evidence to support the thesis that there is a net retention or "salvage" of the urea nitrogen liberated. Our measurements revealed little or no urea hydrolysis during the fed 12-h period of the 24-h tracer protocol but substantial hydrolysis during the 12-h fasting phase. Furthermore, a mass balance model and calculations (APPENDIX) indicated that nitrogen salvage, if any, is quantitatively indistinguishable from insensible nitrogen losses and aggregate estimation errors, accounting for no more than 5% of the nitrogen intake. We conclude that urea hydrolysis, via the intestinal microflora, although representing a component of the overall cycles of nitrogen flow within the body, does not contribute via a net retention of amino nitrogen to the maintenance of body nitrogen homeostasis in healthy adults consuming an adequate diet.

Adult↗
PubMed1996

Quantitative aspects of interorgan relationships among arginine and citrulline metabolism.

The quantitative roles of the splanchnic region and the kidneys in whole body (WB) arginine and citrulline metabolism were assessed in postabsorptive mongrel dogs with primed constant intravenous infusions of [15N2-guanidino, 5,5-2H2]arginine and [13C-ureido]citrulline or [13C-guanidino]arginine and [15N]urea tracers. Isotope and metabolite concentration balances of arginine and citrulline were measured across the gut, liver, splanchnic region, and kidneys, together with WB arginine and citrulline fluxes and urea production rate. The WB citrulline flux and rate of citrulline to arginine (C-A) conversion were 16 and 9.4 mumol.kg-1.h-1, respectively. Concentration balance of citrulline across kidneys was +8.2 mumol.kg-1.h-1, and metabolism of citrulline by kidneys was 8.7 mumol.kg-1.h-1, which was derived about equally from intestine and liver. The appearance rate of citrulline-derived arginine in renal vein was 6.8 mumol.kg-1.h-1. These three separate estimates of C-A conversion within the kidneys were in good agreement, indicating 40% of blood C-A conversion occurring outside kidneys. These findings of interorgan metabolism are discussed in reference to the current knowledge derived largely from studies in laboratory rodents.

Animals↗
PubMed1996

How is lean body mass conserved with the very-low protein diet regimen?

Eight CRF patients (GFR = 18.8 +/- 2.7 ml/min) underwent a crossover comparison of a very-low-protein diet (VLPD) providing 0.28 g protein and 35 kcal/kg/day, plus an isomolar mixture of ketoacids (KA) or essential amino acids (EAA). During each dietary period, a 5-day nitrogen balance (BN) was performed and whole-body protein turnover (WBPT) was measured during fasting and feeding using intravenous [1-13C]leucine and intragastric [5,5,5-2H3]leucine. Although the VLPD/KA regimen contained 15% less nitrogen, BN was neutral and did not differ between the regimens. Similarly, rates of WBPT did not differ between the KA or EAA regimens, and neutral BN was achieved by a marked suppression of amino acid oxidation and postprandial inhibition of protein degradation (PD). Participants were then discharged on the VLPD/KA regimen and monitored as outpatients for > or = 1 year. Repeat BN was neutral and rates of WBPT did not differ from baseline values. Thus, the adaptive responses to dietary protein restriction are sustained during long-term therapy.

Adult↗
PubMed1996

Arginine: new and exciting developments for an "old" amino acid.

Arginine (2-amino-5-guanidino pentanoic acid) was shown in 1895 by Hedin to be present in the proteins of horn. Metabolic nitrogen balance studies, conducted in 1957 by Rose in human adults and in 1959 by Snyderman and coworkers in young infants revealed that a dietary source of this amino acid was not an obligatory requirement for growth and maintenance of nitrogen homeostasis in healthy individuals. Hence, it was initially classified as a non-essential (dispensable) amino acid and, perhaps, for reasons of this classification arginine did not receive the earlier attention it now deserves, in relation to an understanding of the nutritional biochemistry and physiology of its metabolism in humans subjects. However, there is currently a considerable interest in the cellular and tissue functions, as well as clinical, therapeutic significance, of arginine. In this paper we review the multiple functions of arginine, including its role in the L-arginine-nitric oxide pathway, cellular regeneration, immune function, protein synthesis and protein breakdown. We then consider some in vivo aspects of the physiology of arginine metabolism, which varies greatly among eukaryotes, with particular reference to humans. Against this background, studies of arginine in the nutrition of humans under various pathophysiological conditions are reviewed briefly. Finally, a new, updated concept for the metabolic basis for the "conditional essentiality" of arginine is proposed.

Arginine↗
PubMed1995

Can amino acid requirements for nutritional maintenance in adult humans be approximated from the amino acid composition of body mixed proteins?

The quantitative needs for the dietary indispensable amino acids in adult human protein nutrition are still poorly established. Tracer studies with 13C-labeled amino acids have been undertaken previously in our laboratories to reevaluate and further determine the minimum physiological needs for selected indispensable amino acids in healthy adult volunteers. For those amino acids that have not yet been studied by this approach we have proposed a tentative set of requirement figures based on considerations of the amino acid composition of body mixed proteins and the rate of obligatory amino acid losses (i.e., losses when the diet contains no proteins or amino acids). Here we provide an argument for, and a justification of, this approach as an interim measure until more comprehensive data become available on the quantitative aspects of amino acid metabolism in healthy humans.

Adult↗
PubMed1995

Plasma arginine and leucine kinetics and urea production rates in burn patients.

We measured plasma arginine and leucine kinetics and rates of urea production (appearance) in 12 severely burned patients (mean body surface burn area, 48%) during a basal state (low-dose intravenous glucose) and while receiving routine, total parenteral nutrition ([TPN] fed state) including an L-amino acid mixture, supplying a generous level of nitrogen (mean, 0.36 g N.kg-1.d-1). The two nutritional states were studied in random order using a primed 4-hour constant intravenous tracer infusion protocol. Stable-nuclide-labeled tracers were L-[guanidino-13C]arginine, L-[1-13C]leucine, [18O]urea, and NaH13CO3 (prime only), with blood and expired air samples drawn at intervals to determine isotopic abundance of arginine, citrulline, ornithine, alpha-ketoisocaproate ([KIC] for leucine), and urea in plasma and 13CO2 in breath. Results are compared with data obtained in these laboratories in healthy adults. Leucine kinetics (flux and disappearance into protein synthesis) indicated the expected higher turnover in burn patients than in healthy controls. Mean leucine oxidation rates are also higher and compared well with values predicted from urea production rates, provided that urea nitrogen recycling via intestinal hydrolysis is taken into account. The plasma urea flux was also higher than for normal subjects. Arginine fluxes as measured in the systemic whole body, via the plasma pool, were correspondingly higher in burned patients than in healthy controls and were in good agreement with values predicted from leucine-KIC kinetics. However, systemic whole-body arginine flux measured via the plasma pool was only 20% of the arginine flux estimated from the urea flux plus the rate of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Phenylalanine and tyrosine kinetics in young men throughout a continuous 24-h period, at a low phenylalanine intake.

We determined the daily rates of whole-body phenylalanine oxidation (phe-Ox) and hydroxylation (phe-OH) in young men receiving [1-13C]phenylalanine and [2H2]tyrosine via primed, constant intravenous (n = 5) or oral (n = 7) infusions for a consecutive 24 h (12-h fast followed by 12-h fed period), and given a low-phenylalanine (21.9 mg.kg-1.d-1), no-tyrosine, but otherwise adequate L-amino acid-based diet for 6 d before the tracer study. Estimates of the daily rates of phe-Ox and phe-OH were significantly higher (P < 0.001) for the subjects receiving the oral tracer, with estimates of phe-Ox obtained with the oral tracer during the 12-h fast period being close to those predicted from similar 24-h leucine kinetic studies (Am J Clin Nutr 1994;59:1000-11). There was generally poor agreement between the measured 24-h rates of phe-Ox and phe-OH compared with the daily rates as predicted from the last hour of the 12-h fast and 5th hour of feeding. From the 24-h data, daily phenylalanine balances were estimated to be positive with the intravenous-tracer protocol and negative with the oral-tracer group. Our results question the adequacy of current international recommendations for aromatic amino acid requirements in healthy adults.

Administration, Oral↗
PubMed1995

Dietary energy requirements of young and older women determined by using the doubly labeled water method.

There is little information on the effects of age on energy requirements in women. This issue was investigated in a cross-sectional study of 10 normal-weight young women aged 25.2 +/- 1.1 y (mean +/- SEM) and 10 normal-weight older women aged 74.0 +/- 1.4 y. In a 9-d study, measurements were made of free-living total energy expenditure (TEE) by using the doubly labeled water technique, body composition by using hydrodensitometry, and resting energy expenditure (REE) by using indirect calorimetry. Mean values for reported levels of strenuous activity were within the expected range in both groups (31 +/- 13 min/d in the young group and 7 +/- 2 min/d in the older group). Energy requirements expressed as the ratio of TEE to REE were 1.80 +/- 0.10 and 1.62 +/- 0.06 (P < 0.01) in the young and older group, respectively. When values for REE predicted from body weight (pREE) were used, as suggested in the current recommended dietary allowances (RDAs), the ratios of TEE to pREE in the two groups were 1.85 +/- 0.10 and 1.54 +/- 0.04 (P < 0.05). The RDAs significantly under-predicted the energy requirements of the young group (P < 0.05), but there was no significant underprediction in the older group. Although obtained in a relatively small number of subjects, these results provide no evidence to indicate that the current RDAs underestimate the energy requirements of older women, in contrast with previous observations of an underestimation of energy requirements by the RDAs in older men.

Adult↗
PubMed1995

The 24-h kinetics of leucine oxidation in healthy adults receiving a generous leucine intake via three discrete meals.

The significance of meal size and frequency for the 24-h leucine tracer-balance technique was examined. Continuous measurements of leucine oxidation throughout a 24-h d were performed in six healthy, young adults who were given a weight-maintaining diet (188 kJ.kg-1.d-1; 1 g protein.kg-1.d-1) for 6 d followed by primed, continuous intravenous infusions of L-[1-13C]leucine and [15N-15N]urea. The 24-h study was started at 1800 on day 6 and three equal discrete meals were given at 2000, 0600, and 1200. Leucine oxidation was assessed from plasma [13C]alpha-ketoisocaproate enrichment and 13CO2 excretion. The mean (+/- SD) leucine oxidation after each meal (over 6 h) was not significantly different (P > 0.5) among the three discrete meals: 20.0 +/- 3.9, 20.2 +/- 1.9, and 20.3 +/- 2.4 mg.kg-1.d-1 for the meals given at 2000, 0600, and 1200, respectively. Twenty-four-hour leucine oxidation was 75.0 +/- 7.8 mg.kg-1.d-1 for a leucine dietary intake of 80 mg.kg-1.d-1 (and approximately 9.7 mg tracer.kg-1.d-1). The 24-h pattern in leucine oxidation was paralleled by plasma leucine concentrations. Further, leucine oxidation and urea excretion predicted relatively similar values for 24-h protein oxidation. These data are compared with results from our similar previous studies using a multiple-small-meal feeding protocol.

Adult↗
PubMed1995

Influence of age on energy requirements.

The effects of aging on energy requirements and energy expenditure were investigated in 35 healthy young men (mean +/- SE age, 22.7 +/- 0.6 y) and elderly men (68.0 +/- 1.5 y). Over a 10-d metabolic balance study, measurements were made of metabolizable energy intake for weight maintenance, total energy expenditure, resting energy expenditure, and thermic effect of feeding. Values for both metabolizable energy intake and total energy expenditure were significantly higher than the current recommended dietary allowance for energy in both age groups (P < 0.01). Total energy expenditures were 14.48 +/- 0.65 and 11.26 +/- 5.40 MJ/d in young and elderly men, respectively. The difference in total energy expenditure between the groups was accounted for by a significant decrease in all the major components of expenditure. These results suggest that the current recommended dietary allowances for energy may underestimate the usual energy needs of healthy adult men.

Adult↗
PubMed1995

Relations among arginine, citrulline, ornithine, and leucine kinetics in adult burn patients.

Plasma fluxes of arginine, citrulline, and leucine, and the rate of conversion of labeled citrulline to arginine (Qcit-->arg) were determined in nine severely burned patients (mean: 56% body surface burn area, mean 10 d postinjury) while they received total parenteral nutrition (TPN) including an L-amino acid mixture that supplied a generous amount of nitrogen (mean: 0.39 +/- 0.02 g.kg-1.d-1). Plasma fluxes were also studied in these patients during a basal state (low-dose intravenous glucose) by using a primed, 4-h constant intravenous tracer-infusion protocol. Stable-nuclide labeled tracers were L-[15N-15N-guanidino,5,5,2H2]arginine; L-[13C-ureido]citrulline; L-[1-13C]leucine; and NaH13CO3 (prime only), with blood and expired air samples drawn at intervals to determine isotopic abundance of arginine, citrulline, ornithine, and alpha-ketoisocaproate (KIC; for leucine) in plasma and 13CO2 in breath. Leucine kinetics (flux and disappearance into protein synthesis) confirmed the anticipated higher protein turnover in these burn patients compared with healthy control subjects. The plasma arginine fluxes were correspondingly higher in burn patients than in healthy control subjects. However, the citrulline flux and rate of conversion of citrulline to arginine were not higher than values obtained in our laboratories in healthy adult subjects. We hypothesize that the higher rates of arginine loss from the body after burn injury would need to be balanced by an appropriate exogenous intake of preformed arginine to maintain protein homeostasis and promote recovery from this catabolic condition.

Adult↗
PubMed1995

Whole body protein synthesis in healthy adult humans: 13CO2 technique vs. plasma precursor approach.

Different methods for the estimation of whole body protein synthesis (PS) in healthy adult humans were simultaneously compared in seven young adult subjects (6 males, 1 female) fed for 6 days a diet providing 1 g protein.kg-1.day-1 and approximately 188 kJ.kg-1.day-1. A 24-h intravenous tracer study with L-[1-13C]leucine was performed starting at 6 P.M. on day 6. During fasted (6 h) and fed (6 h) steady states, PS was estimated using an approach based on 13CO2 excretion (PSexcr) and on urinary nitrogen excretion data (corrected for changes in body urea pool). Simultaneously, we used the conventional two-pool model and plasma [13C]ketoisocaproate enrichment for estimating PS. The latter mean estimates of PS were significantly higher than PSexcr during fasting [861 +/- 58 (SD) vs. 663 +/- 160 mg protein.kg-1.6 h-1; P < 0.01] and feeding (985 +/- 63 vs. 779 +/- 127 mg protein.kg-1.6 h-1; P < 0.01) and were much less variable. In hourly small-meal feeding, urinary nitrogen excretion was not a reliable index of body protein oxidation when measured over short periods of 6 h, thereby introducing a lack of precision in PSexcr. We suggest that application of the 13CO2 technique to measure PS in humans is limited by the need for relatively prolonged experimental periods of urine collection and tracer infusion within a given physiological state.

Adult↗
PubMed1995

Plasma arginine, citrulline, and ornithine kinetics in adults, with observations on nitric oxide synthesis.

The plasma fluxes of ornithine (Orn), arginine (Arg), and citrulline (Cit) and rate of conversion of labeled ornithine-to-citrulline (QOrn-->Cit) were estimated in six healthy adult men receiving an arginine-rich or arginine-free L-amino acid-based diet, each for 6 days. On day 7 an 8-h (3-h fast, 5-h fed) primed continuous intravenous infusion of L-[guanido-15N,15N] arginine, L-[ureido-13C]citrulline, L-[5,5,2H2]ornithine, and L-[5,5,5-2H3]leucine was conducted. Mean citrulline fluxes (mumol.kg-1.h-1) were 10.4-13.6 for the various conditions and/or diets and remained unchanged (P > 0.05). Arginine flux was lowered (P < 0.01) by 38% for fed state during arginine-free period. Ornithine fluxes for arginine-rich were (P < 0.01) reduced with the arginine-free diet. Rates of QOrn-->Cit declined by 30% (P < .05) during the fed arginine-free period. Short-term restriction in the dietary supply of arginine did not alter the rate of whole body nitric oxide synthesis. One subject showed a very high output of nitrate on arginine-free diet (6 times average for remaining subjects).

Adult↗
PubMed1995

Long-term adaptive responses to dietary protein restriction in chronic renal failure.

Six patients with chronic renal failure (glomerular filtration rate 18 +/- 2 ml/min) underwent two 10-day admissions separated by at least 1 yr of outpatient therapy with a very low-protein diet (VLPD) providing 0.28 g protein.kg-1.day-1 plus an amino acid-ketoacid supplement. During each Clinical Research Center admission, subjects completed a 5-day nitrogen balance (BN), and whole body protein turnover was measured during fasting and feeding using intravenous [1-13C]leucine and intragastric [5,5,5-2H3]leucine. Outpatient dietary protein compliance was very good (25 vs. 20 g protein/day or 125% goal), whereas energy intake was only 69% of goal (24 vs. 35 kcal.kg-1.day-1). During the 16 +/- 2 mo of dietary therapy, there were no changes in serum proteins or anthropometrics. BN after > or = 1 yr of dietary therapy was neutral and did not differ from initial values (+0.46 +/- 0.20 vs. +0.55 +/- 0.19 g N/day). Similarly, rates of whole body protein synthesis, degradation, and leucine oxidation after long-term therapy with the VLPD regimen did not differ from baseline values, and neutral BN was maintained by a marked suppression of amino acid oxidation and postprandial inhibition of protein degradation. This is the first evidence that the compensatory changes in whole body protein turnover activated in response to dietary protein restriction are sustained during long-term therapy.

Adaptation, Physiological↗
PubMed1995

Effects of resistance training and dietary protein intake on protein metabolism in older adults.

Nitrogen (N) balance, fed-state leucine kinetics, and urinary 3-methylhistidine (3-MeH) excretion were examined in 12 men and women, aged 56-80 yr, before and during 12 wk of resistance training (RT). Subjects were randomized to groups that consumed diets providing either 0.80 +/- 0.02 g protein.kg-1.day-1 (lower protein, LP) or 1.62 +/- 0.02 g protein.kg-1.day-1 (higher protein, HP). At baseline, mean N balance was negative for LP (-4.6 +/- 3.4 mg N.kg-1.day-1) and positive for HP (13.6 +/- 1.0 mg N.kg-1.day-1). N retention increased similarly in LP and HP at the 11th wk of RT by 12.8 and 12.7 mg N.kg-1.day-1, respectively. Thus LP had an increased efficiency of N retention. LP had decreased leucine flux (P < 0.001), oxidation (P < 0.001), and uptake for protein synthesis (P < 0.02), relative to HP, both at baseline and after RT. Leucine flux increased with RT in both diet groups (P < 0.05) and was associated mainly with an increase in protein synthesis in LP (91% of change in flux) and an increase in oxidation in HP (72% of change in flux; RT-diet interaction, P < 0.05). RT increased actomyosin protein breakdown (increased 3-MeH-to-creatinine ratio, P < 0.01). Diet-related differences in protein metabolism did not influence body composition changes with RT. These data show that the efficiency of N retention and protein utilization during RT is higher in older subjects who consume 0.8 vs. 1.6 g protein.kg-1.day-1 dietary protein.

Aged↗
PubMed1995

Urea cycle intermediate kinetics and nitrate excretion at normal and "therapeutic" intakes of arginine in humans.

We investigated the effects of a high dietary supplement of arginine on plasma arginine, ornithine, and leucine kinetics and on urea production and excretion in five healthy young adult men. Subjects received either 56 or 561 mg arginine.kg-1.day-1 for 6 days via a complete L-amino acid diet, and on day 7 a tracer protocol (first 3 h fasted; next 5 h fed) was conducted, involving primed constant intragastric infusions of L-[15N2-guanidino,5,5-2H2]arginine, L-[5-13C]ornithine, L-[5,5,5-2H3]leucine, and [15N2]urea, with a prime of H13CO3. Plasma arginine and ornithine fluxes increased significantly (P < 0.05) with arginine supplementation, as did the rate of conversion of plasma labeled arginine to ornithine (P < 0.05) and rate of ornithine oxidation (P < 0.001). However, absolute changes in ornithine kinetics were less than those for arginine or those based on changes expected from the change in arginine intake, implying a complex compartmentation in both whole body arginine and ornithine metabolism. The plasma NO3 concentration, daily output of total NO3, and conversion of [15N]arginine to NO3 did not differ between the diets. Urea production and excretion were reduced significantly with arginine supplementation, suggesting an anabolic effect on the whole body nitrogen economy, possibly via the raised plasma insulin levels (P = 0.013) during the prandial phase.

Adult↗