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Biomedical subjects

V R Young

Publications and source records attributed to V R Young.

At least 19 recordsLinked to original sources

Phenylalanine and tyrosine kinetics in relation to altered protein and phenylalanine and tyrosine intakes in healthy young men.

Plasma phenylalanine (Phe) and tyrosine (Tyr) turnover and the rate of conversion of phenylalanine to tyrosine (Phehyd) and of phenylalanine oxidation (Pheox) after reduced intakes of Phe and Tyr were determined in a metabolic study involving five healthy young adult men. In a pilot study, six postabsorptive young men received either 12- or 4-h infusions of [2H2]Phe and [1-13C]Tyr or [1-13C]Phe and [2H2]Tyro. From these results a primed 8-h constant infusion of [1-13C]Phe and [2H2]Tyr and [2H3]leucine was used in the metabolic study (first 3 h fasted, the 5 h fed) at the end of 1-wk periods during which subjects received an adequate nitrogen L-amino acid based-diet followed by a restricted intake of Phe and Tyr. This procedure was again repeated after 1 and 3 wk when subjects were given a diet low in both nitrogen and Phe and Tyr. Phe and Tyr fluxes were not significantly affected by diet during the fasted metabolic state but Tyr fluxes were lower when the restricted intakes were given. Compared with the rate during the fasting state, Pheox was significantly higher (P less than 0.01) when the adequate diet was consumed; Pheox and Phehyd for fed and fasted states were similar when Phe and Tyr were restricted.

Adult

Energy requirements in the elderly.

The major components of daily energy expenditure may change during aging. A review of current estimates of energy requirements leads to the conclusion that direct estimates of daily energy expenditure are desirable to confirm the validity of the present recommendations. A more extensive examination of the metabolic and nutritional significance of the major food fuel sources is necessary to further define human energy needs.

Aged

Splanchnic and whole body L-[1-13C,15N]leucine kinetics in relation to enteral and parenteral amino acid supply.

The effect of the route of administration of a complete amino acid solution (0.24 g.kg-1.h-1) on leucine (Leu) and alpha-ketoisocaproate (KIC) metabolism in the splanchnic region (Sp) was assessed in nine chronically catherized mongrel dogs receiving, for 6 h, amino acids by jugular vein (PN feeding). Results were compared with those obtained previously [Y. M. Yu, D. A. Wagner, E. E. Tredget, J.A. Waleszewski, J. F. Burke, and V. R. Young. Am. J. Physiol. 259 (Endocrinol. Metab. 22): E36-E51, 1990] in eight dogs similarly studied but given amino acids by constant enteral feeding (EN). We used primed continuous intravenous infusions of L-[1-13C,15N]Leu and measurements of arteriovenous isotope and Leu balance across the gut, liver, and Sp to estimate parameters of whole body and organ Leu metabolism [Leu-N and Leu-C flux, Leu----KIC; KIC----Leu, Leu oxidation and rates of Leu appearance (B) from and disappearance (S) into proteins]. Whole body Leu kinetics were the same for both routes of amino acid administration. With PN, KIC----Leu, Leu----KIC, and total metabolic processing were lower than for EN in Sp, and overall Leu balance (S - B) was higher in Sp for EN. Leu appearance from protein breakdown in gut was higher with PN. The rate of KIC----Leu was higher in liver for EN. These findings reveal that route of amino acid (Leu) administration, under these acute feeding conditions, alters the processing and metabolic fate of Leu in Sp but that whole body parameters of Leu metabolism are stable. The implications of these metabolic findings in relation to the maintenance of intestinal function and integrity are discussed.

Amino Acids

Underfeeding and body weight regulation in normal-weight young men.

The mechanisms of energy regulation invoked by moderate dietary restriction were investigated in seven healthy young men of normal body weight leading unrestricted lives. Following a baseline period of weight maintenance, subjects were underfed by 806 +/- 162 (mean +/- SE) kcal/day for 21 days. Changes in total energy expenditure (TEE) and resting energy expenditure (REE) and subsequent voluntary nutrient intakes were measured. The REE, averaged for fasting and fed states, decreased during underfeeding by 100 +/- 29 kcal/day (P less than 0.01). TEE decreased nonsignificantly by 296 +/- 170 kcal/day, equivalent to an average of 37% of the decrease in energy intake. Body energy stores were estimated to decrease by 510 +/- 172 kcal/day (P less than 0.03), thus compensating for 63% of the dietary energy deficit on average. Voluntary energy intake following dietary restriction increased above the initial amount required for body weight maintenance, was proportional to the weight loss during underfeeding (P less than 0.03), and was associated with a rapid regain of weight lost during underfeeding. These results indicate that energy balance is regulated by adaptive variations in both energy intake and energy expenditure in normal-weight young men leading unrestricted lives but do not support the hypothesis that energy-wasting mechanisms contribute substantially to body energy regulation.

Adult

What are the dietary energy needs of elderly adults?

The energy requirements of healthy elderly men were investigated by measuring total energy expenditure (TEE), body composition and resting energy expenditure (REE), using 2H2(18)O techniques and indirect calorimetry during ten days when a weight maintaining diet was consumed. Values for TEE/REE (1.75 +/- 0.05, s.e.) were significantly higher than the recommended dietary allowances (RDAs) for energy in this age group, as were previously reported values for TEE/REE in a group of young men in the same experimental protocol. There was a significant negative association between TEE/REE (a physical activity indicator) and body fat mass. Combining data from the elderly men in this study and the young men studied previously, age and TEE/REE together accounted for 73% of the variation in body fat mass between individuals. These results lend additional weight to the suggestion that the current RDAs for energy may significantly under-estimate usual energy requirements. They also indicate that the low levels of energy expenditure suggested by the RDAs may favour unnecessarily high levels of body fat mass and that increased levels of energy expenditure are desirable.

Adipose Tissue

Microderivatization of 4-[18O]hydroxyproline and quantitation with a benchtop mass spectrometer.

Accurate estimation of in vivo turnover rates of collagen is complicated by amino acid reutilization. It was previously shown that the ideal, non-recycling tracer was [18O]hydroxyproline synthesized in vivo. The analytical method for measuring turnover rates with [18O]hydroxyproline must include analyte quantitation for pool size determination and isotope ratio measurement for determining levels of label incorporation. For ease of use and widest availability, a benchtop gas chromatograph-mass spectrometer in the electron-impact ionization mode was chosen. Here we present a versatile procedure for hydroxyproline derivatization that is well suited for routine, large-scale determination of analyte concentrations and relative levels of 18O incorporation.

Animals

Nutrient interactions with reference to amino acid and protein metabolism in non-ruminants; particular emphasis on protein-energy relations in man.

Because the regulation of protein and energy balance is of major research interest in the nutrition and physiology of humans and animals, a selected account of interactions between protein and energy is given here, with particular emphasis on studies in human subjects. The discussion begins with reference to the relations between protein and energy intakes and nitrogen balance; selected aspects of the relations between protein dynamics and energy metabolism among the various mammalian species are then considered. This leads to a brief account of oxidative amino acid catabolism and its relevance to the assessment of amino acid requirements, particularly in adult man. It is concluded that obligatory oxidative losses of amino acids can be used to predict or approximate amino acid requirements in children and adults. The nitrogen-sparing properties of carbohydrate and lipid-derived fuels are then considered. Despite the well-known and profound, yet differential, impacts of dietary protein and energy sources, and their interactions on body protein balance, there remain wide gaps in our understanding of the mechanisms responsible for their effects, such as the quantitative and mechanistic involvement of hormones, including insulin and the counter-regulatory hormones, and the roles played by the major amino acids responsible for the interorgan transport of nitrogen and the regulation of urea production. Additional studies focusing on metabolic nitrogen trafficking would significantly enhance an understanding of how protein and energy interact to achieve the efficient utilization of dietary protein for maintenance and promotion of lean body gain.

Alanine

Methionine kinetics and balance at the 1985 FAO/WHO/UNU intake requirement in adult men studied with L-[2H3-methyl-1-13C]methionine as a tracer.

The upper range of the requirement for methionine plus cystine in healthy adults was proposed in 1985 by FAO/WHO/UNU to be 13 mg.kg body wt-1.d-1. To explore the validity of this estimate, five healthy, young adult men were given for 7 d a diet based on an L-amino acid mixture supplying 13 mg methionine.kg-1.d-1 (87 mumol.kg-1.d-1) without cystine. Constant intravenous infusions of L-[2H3-methyl-1-13C]methionine were given on days 5 and 7 while subjects were in the fed and postabsorptive states, respectively. Estimates were made of methionine oxidation, and daily methionine balance was derived from the intake-oxidation data. For the five subjects, methionine balances were -0.9, +0.7, +3.5, -3.1, and -3.8 mg kg-1.d-1, or -6, +5, +23, -21, and -26 mumol.kg-1.d-1. These findings lead to the conclusion that the upper range of the requirement for methionine plus cystine probably exceeds 13 mg.kg-1.d-1 in healthy young adults. The implications of this conclusion for establishing an appropriate amount of sulfur amino acids in an amino acid requirement pattern for adults is discussed.

Adult

Methionine kinetics in adult men: effects of dietary betaine on L-[2H3-methyl-1-13C]methionine.

The effects of a daily 3-g supplement of betaine on kinetic aspects of L-[2H3-methyl-1-13C]methionine (MET) metabolism in healthy young adult men were explored. Four groups of four subjects each were given a control diet, based on an L-amino acid mixture supplying 29.5 and 21.9 mg.kg-1.d-1 of L-methionine and L-cystine for 4 d before the tracer study, conducted on day 5 during the fed state. Two groups received the control diet and two groups received the betaine supplement. Tracer was given intravenously (iv) or orally. The transmethylation rate of MET (TM), homocysteine remethylation (RM), and oxidation of methionine were estimated from plasma methionine labeling and 13C enrichment of expired air. RM tended to increase (P = 0.14) but the TM and methionine oxidation were significantly (P less than 0.05) higher after betaine supplementation when estimated with the oral tracer. No differences were detected with the intravenous tracer. Methionine concentration in plasma obtained from blood taken from subjects in the fed state was higher (P less than 0.01) with betaine supplementation. These results suggest that excess methyl-group intake may increase the dietary requirement for methionine.

Adult

Branched-chain amino acid interactions with reference to amino acid requirements in adult men: valine metabolism at different leucine intakes.

We explored whether the oxidation of valine and by implication the physiological requirement for this amino acid are affected by changes in leucine intake over a physiological range. Six young adult men received, in random order, four L-amino acid-based diets for 5 d supplying either 20 or 10 mg valine.kg body wt-1.d-1, each in combination with 80 or 40 mg leucine.kg-1.d-1. On day 6 subjects were studied with an 8-h continuous intravenous infusion of [1-13C]valine (and [2H3]leucine) to determine valine oxidation in the fasted state (first 3 h) and fed state (last 5 h). Valine oxidation in the fasted state was similar among all diets but was lower (P less than 0.05) in the fed state for the 10 vs 20 mg valine.kg-1.d-1 intake. Leucine intake did not affect valine oxidation. Mean daily valine balance approximated +1.3 mg.kg-1.d-1 for the 20-mg intake and -1.6 mg.kg-1.d-1 for the 10-mg intake. These findings support our previously suggested mean valine requirement estimate of approximately 20 mg.kg-1.d-1.

Adult

Branched-chain amino acid interactions with reference to amino acid requirements in adult men: leucine metabolism at different valine and isoleucine intakes.

Recent estimates of the leucine requirement of adult men based on 13C-tracer studies are substantially higher than those proposed by FAO/WHO/UNU (1985). To explore whether leucine oxidation and requirements are affected by the dietary amount of valine. 11 healthy young adult men received, in random order, for 5 d, one of four L-amino acid diets providing 40 or 15 mg leucine.kg-1.d-1 together with variable amounts mg.kg-1.d-1 of valine and isoleucine in the following combinations (Val:Ile): 80:62 and 20:62 (six subjects; phase 1); 20:62 and 20:20 (five subjects, phase 2). On the morning of day 6, a continuous intravenous infusion of L-[1-13C]leucine was given for 7-8 h; the subject was in the fasting state for the initial 2.5 or 3 h and in the fed state for the remainder of the time. Also, [2H3]leucine was added to the diet. Leucine oxidation was similar for all diet groups in the fasted state. During the fed state, leucine oxidation was not affected by the Val:Ile pattern. Thus, changes in the pattern of branched-chain amino acid intake within a physiological range do not affect isotopically derived estimates of the leucine requirement.

Adult

Proline metabolism in adult male burned patients and healthy control subjects.

Postabsorptive proline flux, oxidation, and endogenous biosynthesis were determined in five severely burned intensive-care-unit patients (mean age 27 y) and in six healthy, young-adult control subjects. Continuous primed, intravenous, 160-min, dual stable-isotope-tracer infusions of L-[1-13C]proline and L-[methyl-2H3]leucine were used in conjunction with measurement of plasma proline concentration and 24-h urinary hydroxyproline output. Burn patients, compared with normal individuals, demonstrated a doubling in proline and leucine flux (P less than 0.01 for both findings), a threefold enhancement of proline oxidation (P less than 0.05), a trend toward decreased proline synthesis, and a 37% reduction in plasma proline concentrations (P less than 0.05). Further, the injured group, unlike the control group, was in a distinct negative body proline balance, as proline oxidation greatly exceeded endogenous proline biosynthesis (P less than 0.01). These studies indicate that significant proline deficits may evolve during the postabsorptive period in severely burned patients and that an exogenous supply of proline might benefit the nitrogen economy of the traumatized patient.

Adult

Dietary energy requirements of young adult men, determined by using the doubly labeled water method.

We examined the hypothesis that current recommendations on dietary energy requirements may underestimate the total energy needs of young adult men, by measuring total energy expenditure (TEE) and resting energy expenditure (REE) in 14 weight-maintaining healthy subjects leading unrestricted lives. TEE and body composition were measured by using 2H(2)18O, and REE was measured by using indirect calorimetry. All subjects had sedentary full-time occupations and participated in strenuous leisure activities for 34 +/- 6 (SE) min/d. TEE and REE were 14.61 +/- 0.76 and 7.39 +/- 0.26 MJ/d, respectively, and 202 +/- 2 and 122 +/- 2 kJ.kg-1.d-1. There were significant relationships between TEE and both body fat-free mass (r = 0.732, P less than 0.005) and measured REE (r = 0.568, P less than 0.05). Measured TEE:REE values were significantly higher than the recommended energy requirement (1.98 +/- 0.09, compared with 1.55 or 1.67, P less than 0.005). These results are consistent with the suggestion that the current recommended energy intake for young adult men may underestimate total energy needs.

Adult

Objective verification of dietary intake by measurement of urine osmolality.

A new method for assessing the accuracy of dietary nutrient intakes in metabolic studies is described. The theoretical basis of the method is the comparison of measurements of the urine osmole excretion rate (OER, the product of urine osmolality and urine weight) with values for OER predicted from dietary nitrogen, sodium, and potassium. The method was tested in 34 healthy male and female volunteers aged 18-78 y who made complete 24-h urine collections and consumed a diet over 6 d in metabolic-balance studies involving either overfeeding, weight maintenance, or weight loss. The coefficients of variation for equations relating measured OER to dietary nitrogen, sodium, and potassium intakes ranged from 14.1% for 1-d measurements to 6.94% for 6-d means. These results indicate that it should be possible to use measurements of the urine OER to identify dietary noncompliance in metabolic studies.

Adolescent