Whole-Body Protein Turnover before and after Resection of Colorectal Tumours

1. The rate of whole-body nitrogen flux; protein synthesis and protein breakdown were measured in patients with colorectal cancer (Dukes A—C) just before and 12 weeks after surgical removal of the tumour. The rates were determined from the urinary excretion of 15N in ammonia and in urea over a 9 h period after an oral dose of [15N]glycine. 2. The food intake during the 2 study days was identical for individual patients. The amount each received was determined from measurement of their intake of food ad libitum on the day preceding the pre-operative study and was consumed in six equal portions every 2 h during the experimental period. 3. No significant differences in the rates of nitrogen flux, protein synthesis and protein breakdown were found before and after tumour resection, whether calculated from the excretion of 15N in ammonia or in urea. Some changes in flux, both increases and decreases, were observed in individual patients after tumour removal but these could not be related to classification of the tumour, or to the presence of pre-operative anorexia or weight loss. 4. The results suggest that the primary tumour itself does not alter the overall rate of protein metabolism in the whole body.

Download Full-text

Enhancement of tumor proteolysis by TNF-alpha: correlation of in vivo isotope estimates with growth

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1991.261.1.r106 ◽

1991 ◽

Vol 261 (1) ◽

pp. R106-R116

Author(s):

N. W. Istfan ◽

P. R. Ling ◽

G. L. Blackburn ◽

B. R. Bistrian

Keyword(s):

Protein Synthesis ◽

Protein Metabolism ◽

Whole Body ◽

Independent Effect ◽

Yoshida Sarcoma ◽

Protein Breakdown ◽

Body Protein ◽

Breakdown Rates ◽

Made In

To evaluate the accuracy of in vivo estimates of protein synthesis and breakdown, measurements of plasma and tissue leucine kinetics were made in rat tumor tissues at different conditions of growth by use of constant intravenous infusion of [14C]leucine. These measurements were made in Yoshida sarcoma tumors on days 10 and 13 after implantation, with and without tumor necrosis factor (TNF) infusion and on day 10 in Walker-256 carcinosarcoma. Expressed as micromoles of leucine per gram tissue, tumor protein breakdown increased (P less than 0.01) from 0.32 +/- 0.02 to 0.52 +/- 0.09 (SE) mumol/h, with progress of the Yoshida sarcoma tumor between days 10 and 13 after implantation. Similarly, TNF increased tumor proteolysis on day 10 (0.43 +/- 0.03 mumol.h-1.g-1, P less than 0.05 vs. day 10 control) but not on day 13 after implantation of the Yoshida tumor. Estimates of growth derived from the difference between protein synthesis and breakdown rates were not statistically different from those based on actual tumor volume changes in both tumor models. However, estimates of “whole body” protein metabolism (plasma leucine flux) were not affected either by tumor aging or by treatment with TNF. This study shows that in vivo estimates of tissue protein metabolism based on our [14C]leucine constant infusion model closely reflect the growth characteristic of that tissue. A cytotoxic perfusion-independent effect for intravenous TNF on growing tumor tissue is demonstrable as increased protein breakdown. Furthermore, the commonly used concept of whole body protein metabolism, derived solely from tracer dilution in plasma, is an oversimplification.

Download Full-text

Prolonged bed rest decreases skeletal muscle and whole body protein synthesis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.270.4.e627 ◽

1996 ◽

Vol 270 (4) ◽

pp. E627-E633 ◽

Cited By ~ 118

Author(s):

A. A. Ferrando ◽

H. W. Lane ◽

C. A. Stuart ◽

J. Davis-Street ◽

R. R. Wolfe

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Bed Rest ◽

Whole Body ◽

Protein Breakdown ◽

Skeletal Muscle Protein ◽

Model Calculations ◽

Body Protein

We sought to determine the extent to which the loss of lean body mass and nitrogen during inactivity was due to alterations in skeletal muscle protein metabolism. Six male subjects were studied during 7 days of diet stabilization and after 14 days of stimulated microgravity (-6 degrees bed rest). Nitrogen balance became more negative (P < 0.03) during the 2nd wk of bed rest. Leg and whole body lean mass decreased after bed rest (P < 0.05). Serum cortisol, insulin, insulin-like growth factor I, and testosterone values did not change. Arteriovenous model calculations based on the infusion of L-[ring-13C6]-phenylalanine in five subjects revealed a 50% decrease in muscle protein synthesis (PS; P < 0.03). Fractional PS by tracer incorporation into muscle protein also decreased by 46% (P < 0.05). The decrease in PS was related to a corresponding decrease in the sum of intracellular amino acid appearance from protein breakdown and inward transport. Whole body protein synthesis determined by [15N]alanine ingestion on six subjects also revealed a 14% decrease (P < 0.01). Neither model-derived nor whole body values for protein breakdown change significantly. These results indicate that the loss of body protein with inactivity is predominantly due to a decrease in muscle PS and that this decrease is reflected in both whole body and skeletal muscle measures.

Download Full-text

Muscle wasting in emphysema

Clinical Science ◽

10.1042/cs0750415 ◽

1988 ◽

Vol 75 (4) ◽

pp. 415-420 ◽

Cited By ~ 73

Author(s):

W. L. Morrison ◽

J. N. A. Gibson ◽

C. Scrimgeour ◽

M. J. Rennie

Keyword(s):

Protein Synthesis ◽

Protein Turnover ◽

Muscle Wasting ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Myofibrillar Protein ◽

Whole Body ◽

Protein Breakdown ◽

Body Protein ◽

Net Protein

1. We have investigated arteriovenous exchanges of tyrosine and 3-methylhistidine across leg tissue in the postabsorptive state as specific indicators of net protein balance and myofibrillar protein breakdown, respectively, in eight patients with emphysema and in 11 healthy controls. Whole-body protein turnover was measured using l-[1-13C]leucine. 2. Leg efflux of tyrosine was increased by 47% in emphysematous patients compared with normal control subjects, but 3-methylhistidine efflux was not significantly altered. 3. In emphysema, whole-body leucine flux was normal, whole-body leucine oxidation was increased, and whole-body protein synthesis was depressed. 4. These results indicate that the predominant mechanism of muscle wasting in emphysema is a fall in muscle protein synthesis, which is accompanied by an overall fall in whole-body protein turnover.

Download Full-text

Postprandial body protein synthesis and amino acid catabolism measured with leucine and phenylalanine-tyrosine tracers

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00416.2002 ◽

2003 ◽

Vol 284 (5) ◽

pp. E1037-E1042 ◽

Cited By ~ 20

Author(s):

Paolo Tessari ◽

Edward Kiwanuka ◽

Michela Zanetti ◽

Rocco Barazzoni

Keyword(s):

Protein Synthesis ◽

Amino Acid ◽

Healthy Subjects ◽

Fixed Ratio ◽

Whole Body ◽

Mixed Meal ◽

Body Protein ◽

Precursor Pool ◽

Amino Acid Data ◽

Before And After

Whether phenylalanine-tyrosine (Phe-Tyr) tracers yield estimates of postprandial protein synthesis comparable to those of the widely used leucine (Leu) tracer is unclear. We measured Leu oxidation (Ox), Phe hydroxylation (Hy), and their disposal into whole body protein synthesis before and after the administration of a mixed meal (62 kJ/kg body wt, 22% of energy as protein), over 4 h in healthy subjects. Both plasma and intracellular precursor pools were used. The amino acid data were extrapolated to body protein by assuming a fixed ratio of Leu to Phe in the proteins. In the postabsorptive state, whole body protein synthesis (expressed as mg · kg−1 · min−1) was similar between Leu and Phe-Tyr tracers irrespective of the precursor pool used. After the meal, Leu Ox, Phe Hy, and body protein synthesis increased ( P ≤ 0.01 vs. basal). With the use of intracellular precursor pools, the increase of protein synthesis with Phe-Tyr (+0.51 ±0.21 mg · kg−1 · min−1) and Leu tracers (+0.57 ± 0.14) were similar ( P = not significant). In contrast, with plasma pools the increase of protein synthesis was more than twofold greater with Phe-Tyr (+1.17 ± 0.19 mg · kg−1 · min−1) than that with Leu (0.50 ± 0.13 mg · kg−1 · min−1, P < 0.01). Direct correlations were found between Leu and Ox [using both plasma and intracellular pools ( r ≤ 0.65, P ≤ 0.01)] but not between Phe and either plasma or intracellular Hy. In conclusion, 1) Phe-Tyr and Leu tracers yield comparable estimates of body protein synthesis postprandially, provided that intracellular precursor pools are used; 2) both Leu Ox and Phe Hy are stimulated by a mixed meal; 3) Phe does not correlate with Hy, which might be better related to the (unknown) portal Phe.

Download Full-text

Protein Metabolism in Human Neonates: Nitrogen-Balance Studies, Estimated Obligatory Losses of Nitrogen and Whole-Body Turnover of Nitrogen

Clinical Science ◽

10.1042/cs0520485 ◽

1977 ◽

Vol 52 (5) ◽

pp. 485-498 ◽

Cited By ~ 8

Author(s):

P. B. Pencharz ◽

W. P. Steffee ◽

W. Cochran ◽

N. S. Scrimshaw ◽

W. M. Rand ◽

...

Keyword(s):

Protein Synthesis ◽

Nitrogen Balance ◽

Growth And Development ◽

Term Infant ◽

Nitrogen Losses ◽

Whole Body ◽

Nitrogen Flux ◽

Body Protein ◽

Mean Values ◽

The Mean

1. Aspects of nitrogen metabolism in the human neonate were assessed in one full-term infant and six premature infants by means of nitrogen-balance measurements, estimates of obligatory nitrogen losses and determinations of whole-body nitrogen turnover. 2. Our data indicate that the mean protein requirement for maintenance is 1·1 g of protein day−1 kg−1 and that 3·8 g of protein day−1 kg−1 should be sufficient for adequate growth in healthy premature babies. 3. The mean obligatory urinary, faecal and total nitrogen losses were estimated to be 24, 106 and 145 mg day−1 kg−1 respectively. These figures are compared with published values for older infants, and the possible metabolic basis for changes in nitrogen losses during growth and development is discussed. 4. Mean values for whole-body protein synthesis and breakdown were 26·3 ± 7·0 and 23·8 ± 7·4 g of protein day−1 kg−1 respectively. Dietary nitrogen intake accounted for 6–18% of the nitrogen flux through the metabolic pool; urea excretion accounted for 2% of the nitrogen flux. 5. The net protein gain, estimated from nitrogen-balance data, accounted for 9·6% of total daily protein synthesis. 6. These results are discussed in relation to published estimates of whole-body protein synthesis and breakdown at various ages. Their possible significance in the assessment of a ‘maintenance’ requirement for protein and amino acids during the period of rapid growth and development is also considered.

Download Full-text

Epidural Ropivacaine versus Epidural Morphine and the Catabolic Response to Colonic Surgery

Anesthesiology ◽

10.1097/00000542-200404000-00031 ◽

2004 ◽

Vol 100 (4) ◽

pp. 973-978 ◽

Cited By ~ 5

Author(s):

Thomas Schricker ◽

Linda Wykes ◽

Leopold Eberhart ◽

Ralph Lattermann ◽

Franco Carli

Keyword(s):

Protein Synthesis ◽

Epidural Analgesia ◽

Protein Oxidation ◽

Glucose Production ◽

Whole Body ◽

Protein Breakdown ◽

Body Protein ◽

Oxidation Rates ◽

Metabolic Substrates ◽

Catabolic Response

Background The authors examined the hypothesis that epidural administration of local anesthetic, in contrast to epidural analgesia with morphine, inhibits postoperative protein oxidation during administration of glucose. Methods Fourteen patients were randomly assigned to undergo a 6-h stable isotope infusion study (3 h fasted, 3 h feeding with 4 mg.kg(-1).min(-1) glucose) on the second day after colorectal surgery using epidural analgesia with either continuous ropivacaine or intermittent morphine. Protein synthesis, breakdown and oxidation, and glucose production were measured by L-[L-13C]leucine and [6,6-2H2]glucose. Substrate oxidation rates were determined by indirect calorimetry. Plasma concentrations of metabolic substrates and hormones were also measured. Results Whole body protein breakdown, oxidation, synthesis, and glucose production in the fasted state were similar between the two groups. Glucose administration decreased protein breakdown (P = 0.01), protein synthesis (P = 0.001), and glucose production (P = 0.001) to the same extent in both groups, whereas protein oxidation was not significantly affected. The type of epidural analgesia did not significantly influence the circulating concentrations of metabolic substrates and hormones in the fasted or in the fed state. Carbohydrate oxidation rate in the ropivacaine group was greater than in patients receiving morphine (P = 0.04), regardless of whether glucose was infused. Conclusion Epidural analgesia achieved with ropivacaine or morphine does not suppress the catabolic response to surgery, either under fasting conditions or in the presence of an energy supply.

Download Full-text

Muscle protein metabolism in female swimmers after a combination of resistance and endurance exercise

Journal of Applied Physiology ◽

10.1152/jappl.1996.81.5.2034 ◽

1996 ◽

Vol 81 (5) ◽

pp. 2034-2038 ◽

Cited By ~ 75

Author(s):

Kevin D. Tipton ◽

Arny A. Ferrando ◽

Bradley D. Williams ◽

Robert R. Wolfe

Keyword(s):

Protein Synthesis ◽

Resistance Training ◽

Endurance Exercise ◽

Protein Metabolism ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Whole Body ◽

Protein Breakdown ◽

Body Protein ◽

Muscle Protein Metabolism

Tipton, Kevin D., Arny A. Ferrando, Bradley D. Williams, and Robert R. Wolfe. Muscle protein metabolism in female swimmers after a combination of resistance and endurance exercise. J. Appl. Physiol. 81(5): 2034–2038, 1996.—There is little known about the responses of muscle protein metabolism in women to exercise. Furthermore, the effect of adding resistance training to an endurance training regimen on net protein anabolism has not been established in either men or women. The purpose of this study was to quantify the acute effects of combined swimming and resistance training on protein metabolism in female swimmers by the direct measurement of muscle protein synthesis and whole body protein degradation. Seven collegiate female swimmers were each studied on four separate occasions with a primed constant infusion of ring-[13C6]phenylalanine (Phe) to measure the fractional synthetic rate (FSR) of the posterior deltoid and whole body protein breakdown. Measurements were made over a 5-h period at rest and after each of three randomly ordered workouts: 1) 4,600 m of intense interval swimming (SW); 2) a whole body resistance-training workout with no swimming on that day (RW); and 3) swimming and resistance training combined (SR). Whole body protein breakdown was similar for all treatments (0.75 ± 0.04, 0.69 ± 0.03, 0.69 ± 0.02, and 0.71 ± 0.04 μmol ⋅ min−1 ⋅ kg−1for rest, RW, SW, and SR, respectively). The FSR of the posterior deltoid was significantly greater ( P< 0.05) after SR (0.082 ± 0.015%/h) than at rest (0.045 ± 0.006%/h). There was no significant difference in the FSR after RW (0.048 ± 0.004%/h) or SW (0.064 ± 0.008%/h) from rest or from SR. These data indicate that the combination of swimming and resistance exercise stimulates net muscle protein synthesis above resting levels in female swimmers.

Download Full-text

Apparent compartmentation of body nitrogen in one human subject: its consequences in measuring the rate of whole-body protein synthesis with 15N

Clinical Science ◽

10.1042/cs0680271 ◽

1985 ◽

Vol 68 (3) ◽

pp. 271-282 ◽

Cited By ~ 66

Author(s):

Edward B. Fern ◽

Peter J. Garlick ◽

John C. Waterlow

Keyword(s):

Protein Synthesis ◽

Experimental Period ◽

Oral Route ◽

The Body ◽

Whole Body ◽

Body Protein ◽

Pool Model ◽

Harmonic Average ◽

Empirical Context ◽

Oral Doses

1. The rate of protein synthesis in the whole body was measured in one fed subject with seven 15N-labelled amino acids (intravenous and oral doses) and two 15N protein mixtures (oral doses only). The rates were determined individually from the urinary excretion of ammonia and total urea over a 12 h experimental period. 2. Except with oral glycine and alanine, the synthesis rates given by ammonia and urea were appreciably different within each study when calculated on the assumption of a single pool of metabolic nitrogen in the body. In general, intravenous administration of the tracers gave higher rates with urea and the oral route gave higher rates with ammonia. 3. The differences between intravenous and oral doses of 15N could be reduced significantly by calculating synthesis rates from either the arithmetic or harmonic average of flux rates given by ammonia and urea. The averages correspond to estimates of the total flux in a two-pool model of metabolic nitrogen when it is assumed either that both pools receive an equal amount of tracer (arithmetic) or that both have the same rate of nitrogen turnover (harmonic). 4. By so reducing the effect of physical separation of nitrogen in the body, the metabolic aspects of compartmentation of the tracer could be examined. The results show that the absolute value obtained for protein synthesis depends on the source of labelled nitrogen. The data are discussed in this empirical context.

Download Full-text

Amino acid metabolism after intense exercise

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1990.258.2.e249 ◽

1990 ◽

Vol 258 (2) ◽

pp. E249-E255 ◽

Cited By ~ 5

Author(s):

J. T. Devlin ◽

I. Brodsky ◽

A. Scrimgeour ◽

S. Fuller ◽

D. M. Bier

Keyword(s):

Protein Synthesis ◽

Amino Acid ◽

Protein Degradation ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Recovery Period ◽

Whole Body ◽

Protein Breakdown ◽

Body Protein ◽

Leucine Oxidation

We studied postexercise amino acid metabolism, in the whole body and across the forearm. Seven volunteers were infused with L-[alpha-15N]lysine and L-[1-13C]-leucine twice [one time during 3 h after cycle exercise (75% VO2max), and one time in the resting state]. Whole body protein breakdown was estimated from dilution of L-[alpha-15N]lysine and L-[1-13C]ketoisocaproic acid (KIC) enrichments in plasma. Leucine oxidation was calculated from 13CO2 enrichments in expired air. Whole body protein breakdown was not increased above resting levels during the recovery period. Leucine oxidation was decreased after exercise (postexercise 13 +/- 2.3 vs. resting 19 +/- 3.2 mumol.kg-1.h-1; P less than 0.02), while nonoxidative leucine disposal was increased (115 +/- 6.1 vs. 103 +/- 5.6 micrograms.kg-1.min-1; P less than 0.02). After exercise, forearm net lysine balance was unchanged (87 +/- 25 vs. 93 +/- 28 nmol.100 ml-1.min-1), but there were decreases in forearm muscle protein degradation (219 +/- 51 vs. 356 +/- 85 nmol.100 ml-1.min-1; P less than 0.05) and synthesis (132 +/- 41 vs. 255 +/- 69 nmol.100 ml-1.min-1; P less than 0.01). In conclusion, after exercise 1) whole body protein degradation is not increased, 2) leucine disposal is directed away from oxidative and toward nonoxidative pathways, 3) forearm protein synthesis is decreased. Postexercise increases in whole body protein synthesis occur in tissues other than nonexercised muscle.

Download Full-text