Whole-body urea cycling and protein turnover during hyperphagia and dormancy in growing bears (Ursus americanus and U. arctos)

1997 ◽  
Vol 75 (12) ◽  
pp. 2129-2136 ◽  
Author(s):  
Perry S. Barboza ◽  
Sean D. Farley ◽  
Charles T. Robbins

Subadult bears were studied during their autumn hyperphagia (n = 3) and winter dormancy (n = 6). Urea kinetics were measured with 14C- and 15N-urea, protein turnover was estimated with 15N-glycine, and body composition was assessed with 3H-water. Reduced amino acid degradation in winter was indicated by declines in plasma urea and aminotransferase activities, and lower urea production than in autumn (4.7 vs. 27.5 mmol urea-N∙kg−0.75∙d−1). Only 7.5% of urea produced in hyperphagic bears was degraded and just 1.1% of the degraded N reutilized as amino-N. Dormant bears reutilized 99.7% of urea produced, indicating thorough microbial ureolysis and urea-N resorption. Low rates of body N loss during dormancy suggested losses of non-urea N as creatinine. Protein turnover rates (15.2–21.5 g∙kg−0.75∙d−1) were similar between seasons and reflected the apparent maintenance of hepatic, intestinal, and muscular functions through dormancy. Protein synthesis accounted for 32% of energy expended in dormancy, which was mainly (91.5%) derived from fat oxidation. Consistent organ function and body temperature in dormant bears enables recycling of urea-N, which minimizes body protein loss and conserves mobility. In comparison with heterothermic hibernation, ursid dormancy would provide greater flexibility during winter and facilitate rapid resumption of foraging and growth in spring.

1987 ◽  
Vol 58 (2) ◽  
pp. 287-300 ◽  
Author(s):  
M. F. Fuller ◽  
P. J. Reeds ◽  
A. Cadenhead ◽  
B. Seve ◽  
T. Preston

1. The interrelations between protein accretion and whole-body protein turnover were studied by varying the quantity and quality of protein given to growing pigs.2. Diets with 150 or 290g lysine-deficient protein/kg were given in hourly meals, with or without lysine supplementation, to female pigs (mean weight 47 kg).3. After the animals were adapted to the diets, a constant infusion of [14C]urea was given intra-arterially for 30 h, during the last 6 h of which an infusion of [4,5-3H] leucine was also infused at a constant rate. At the same time, yeast-protein labelled with15N was given in the diet for 50 h.4. The rate of urea synthesis was estimated from the specific radioactivity (SR) of plasma urea. The rate of leucine flux was estimated from the SR of plasma leucine. The irrevocable breakdown of leucine was estimated from the3H-labelling of body water. Total N flux was estimated from the16N-labelling of urinary urea.5. Addition of lysine to the low-protein diet significantly increased N retention, with a substantial reduction in leucine breakdown, but there was no significant change in the flux of leucine or of total N.6. Increasing the quantity of the unsupplemented protein also increased N retention significantly, with concomitant increases in leucine breakdown and in the fluxes of leucine and of total N.7. It is concluded that a doubling of protein accretion brought about by the improvement of dietary protein quality is not necessarily associated with an increased rate of whole-body protein turnover.


2017 ◽  
Vol 176 (4) ◽  
pp. 489-496 ◽  
Author(s):  
Teresa Lam ◽  
Anne Poljak ◽  
Mark McLean ◽  
Neha Bahl ◽  
Ken K Y Ho ◽  
...  

ContextThe urea cycle is a rate-limiting step for amino acid nitrogen elimination. The rate of urea synthesis is a true indicator of whole-body protein catabolism. Testosterone reduces protein and nitrogen loss. The effect of testosterone on hepatic urea synthesis in humans has not been studied.ObjectiveTo determine whether testosterone reduces hepatic urea production.DesignAn open-label study.Patients and interventionEight hypogonadal men were studied at baseline, and after two weeks of transdermal testosterone replacement (Testogel, 100 mg/day).Main outcomes measuresThe rate of hepatic urea synthesis was measured by the urea turnover technique using stable isotope methodology, with15N2-urea as tracer. Whole-body leucine turnover was measured, from which leucine rate of appearance (LRa), an index of protein breakdown and leucine oxidation (Lox), a measure of irreversible protein loss, were calculated.ResultsTestosterone administration significantly reduced the rate of hepatic urea production (from 544.4 ± 71.8 to 431.7 ± 68.3 µmol/min;P < 0.01), which was paralleled by a significant reduction in serum urea concentration. Testosterone treatment significantly reduced net protein loss, as measured by percent Lox/LRa, by 19.3 ± 5.8% (P < 0.05). There was a positive association between Lox and hepatic urea production at baseline (r2 = 0.60,P < 0.05) and after testosterone administration (r2 = 0.59,P < 0.05).ConclusionTestosterone replacement reduces protein loss and hepatic urea synthesis. We conclude that testosterone regulates whole-body protein metabolism by suppressing the urea cycle.


1989 ◽  
Vol 67 (6) ◽  
pp. 624-628 ◽  
Author(s):  
P. Pencharz ◽  
J. Beesley ◽  
P. Sauer ◽  
J. Van Aerde ◽  
U. Canagarayar ◽  
...  

Protein turnover rates in neonates have been calculated largely by measuring urinary [15N]urea enrichment following administration of [15N]glycine. Although ammonia has been increasingly recognized as an end product of nitrogen metabolism, in neonates it yields a different estimate of protein turnover than does urea. Comparisons of ammonia and urea end products in parenterally fed neonates have not previously been reported. A third and independent way of estimating protein turnover, developed for adults, is to use breath 13CO2 as an end product following administration of [1-3C]leucine. We therefore carried out simultaneous measurements of protein turnover in 10 parenterally fed neonates, using the three end products. The infants were clinically stable, weighed 2.6 ± 0.2 kg, and received 3.1 ± 0.2 g∙kg−1∙d−1 of amino acid, 2.2 ± 0.1 g∙kg−1∙d−1 of lipids, and an energy intake of 90 ± 4 kcal∙kg−1∙d−1 (1 kcal = 4.186 kJ). The turnover estimates derived from the 13CO2 and [15N]urea end products were very similar. The [15N]ammonia end product produced values approximately 66% (p < 0.01) of the other two. We conclude that the ammonia and urea end products probably originate in different precursor pools. The similarity of the urea and breath carbon dioxide results helps validate the use of the urea end product in studying the nitrogen metabolism of parenterally fed neonates. Ideally in future studies two or more end products should be used, since they provide information about different aspects of the nenonates' protein metabolism.Key words: neonates, protein metabolism, nitrogen-15, [1-13C]leucine.


2000 ◽  
Vol 278 (3) ◽  
pp. E477-E483 ◽  
Author(s):  
Rhonda C. Vann ◽  
Hanh V. Nguyen ◽  
Peter J. Reeds ◽  
Douglas G. Burrin ◽  
Marta L. Fiorotto ◽  
...  

Somatotropin (ST) administration enhances protein deposition in well-nourished, growing animals. To determine whether the anabolic effect is due to an increase in protein synthesis or a decrease in proteolysis, pair-fed, weight-matched (∼20 kg) growing swine were treated with porcine ST (150 μg ⋅ kg− 1 ⋅ day− 1, n = 6) or diluent ( n = 6) for 7 days. Whole body leucine appearance (Ra), nonoxidative leucine disposal (NOLD), urea production, and leucine oxidation, as well as tissue protein synthesis (Ks), were determined in the fed steady state using primed continuous infusions of [13C]leucine, [13C]bicarbonate, and [15N2]urea. ST treatment increased the efficiency with which the diet was used for growth. ST treatment also increased plasma insulin-like growth factor I (+100%) and insulin (+125%) concentrations and decreased plasma urea nitrogen concentrations (−53%). ST-treated pigs had lower leucine Ra (−33%), leucine oxidation (−63%), and urea production (−70%). However, ST treatment altered neither NOLD nor Ks in the longissimus dorsi, semitendinosus, or gastrocnemius muscles, liver, or jejunum. The results suggest that in the fed state, ST treatment of growing swine increases protein deposition primarily through a suppression of protein degradation and amino acid catabolism rather than a stimulation of protein synthesis.


1979 ◽  
Vol 57 (3) ◽  
pp. 281-283 ◽  
Author(s):  
M. Taruvinga ◽  
A. A. Jackson ◽  
M. H. N. Golden

1. Whole-body protein turnover was measured in rats by constant infusion of 15N-labelled glycine, aspartate, valine and leucine and measuring the enrichment of hepatic and renal urea and ammonia nitrogen. 2. The values obtained with [15N]glycine were comparable with values reported with methods based on different assumptions. 3. [15N]Aspartate gave rise to an increased enrichment of urea and ammonia and hence to lower protein-turnover rates. 4. [15N]Valine and [15N]leucine gave low enrichments of nitrogenous end products and hence to high protein-turnover rates. 5. All 15N-labelled amino acids are not equally suitable for measuring whole-body protein turnover by the end-product method. The relative amounts of 15N going to the end products can be predicted from the known individual metabolism of aspartate and the branched-chain amino acids.


1998 ◽  
Vol 275 (2) ◽  
pp. E310-E320 ◽  
Author(s):  
Anders H. Forslund ◽  
Leif Hambraeus ◽  
Roger M. Olsson ◽  
Antoine E. El-Khoury ◽  
Yong-Ming Yu ◽  
...  

In healthy adult men adapted to a diet/exercise regimen for 6 days, the effects of small, frequent meals supplying daily protein intakes of 1 ( n = 8) or 2.5 g ⋅ kg−1 ⋅ day−1( n = 6) on leucine oxidation, urea production, and whole body protein synthesis (PS) and degradation (PD) have been compared with the use of a 24-h continuous intravenous [13C]leucine and [15N,15N]urea infusion protocol. Two 90-min periods of exercise (∼50% maximal O2 consumption) were included during the fasting and the fed periods of the 24-h day. Subjects were determined to be at approximate energy, nitrogen, and leucine balances on both diets. Increased protein intake raised the urea production rate; the absolute rate of urea hydrolysis was the same on both diets. When the first-pass splanchnic uptake of leucine was taken to be 25% of intake, PS was stimulated by feeding (after an overnight fast) at both protein intake levels ( P < 0.05 and P < 0.01), whereas PD declined significantly ( P < 0.01) at both protein levels. Protein gain at a high protein intake appears to be the result of both a stimulation of PS and a marked decline in PD, whereas at a less generous intake, the gain appears to be a result of a fall in PD with a less evident change in PS. Exercise moderately decreased PS during and/or immediately after exercise at each protein level, and there was a postexercise-induced increase ( P < 0.01) in PD, which was more dramatic when feeding was at the higher protein intake level.


2019 ◽  
Vol 8 (5) ◽  
pp. 605-615 ◽  
Author(s):  
Teresa Lam ◽  
Mark McLean ◽  
Amy Hayden ◽  
Anne Poljak ◽  
Birinder Cheema ◽  
...  

Context Androgen deprivation therapy (ADT) in prostate cancer results in muscular atrophy, due to loss of the anabolic actions of testosterone. Recently, we discovered that testosterone acts on the hepatic urea cycle to reduce amino acid nitrogen elimination. We now hypothesize that ADT enhances protein oxidative losses by increasing hepatic urea production, resulting in muscle catabolism. We also investigated whether progressive resistance training (PRT) can offset ADT-induced changes in protein metabolism. Objective To investigate the effect of ADT on whole-body protein metabolism and hepatic urea production with and without a home-based PRT program. Design A randomized controlled trial. Patients and intervention Twenty-four prostate cancer patients were studied before and after 6 weeks of ADT. Patients were randomized into either usual care (UC) (n = 11) or PRT (n = 13) starting immediately after ADT. Main outcome measures The rate of hepatic urea production was measured by the urea turnover technique using 15N2-urea. Whole-body leucine turnover was measured, and leucine rate of appearance (LRa), an index of protein breakdown and leucine oxidation (Lox), a measure of irreversible protein loss, was calculated. Results ADT resulted in a significant mean increase in hepatic urea production (from 427.6 ± 18.8 to 486.5 ± 21.3; P < 0.01) regardless of the exercise intervention. Net protein loss, as measured by Lox/Lra, increased by 12.6 ± 4.9% (P < 0.05). PRT preserved lean body mass without affecting hepatic urea production. Conclusion As early as 6 weeks after initiation of ADT, the suppression of testosterone increases protein loss through elevated hepatic urea production. Short-term PRT was unable to offset changes in protein metabolism during a state of profound testosterone deficiency.


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