Total Body Protein Turnover Research Articles

327 Parameter Updates in the Davis Growth Model for Growth, Intake, and Composition of Modern Angus-Cross Cattle

Abstract The Davis Growth Model is a dynamic model used to estimate body composition and growth in beef cattle by simulating total body DNA and protein turnover. Since model development and parametrization in the 1980s, the model has been re-structured to account for previous rate of protein accretion and prior nutrition. Original parameter estimates for alpha (maintenance constant, where net energy for maintenance is alpha x shrunk body weight0.75; 0.08406) and K2 (protein synthesis rate constant; 0.0444) may not fit modern, heavier, more productive cattle. Angus-cross steers (n = 24; initial body weight 402 ± 12 kg) were fed using automated feed weight stations in group pens (8 steers/pen). Steers were fed a high energy ration twice daily, at 10% greater than the intake from the previous day. Steers were measured for hip height, body weight (BW), and ultrasonic measurements for ribeye area and back fat every 28 d until harvest (d 128). These measurements were used to calculate empty BW, empty body fat, and empty percent body fat for alpha and K2 estimates. Parameter estimates (± SD) were 0.12661 (0.01587) and 0.04919 (0.00220) for alpha and K2, respectively. Parameter estimates in the current study reflect a large increase in apparent maintenance. Maintenance requirements were moderately correlated with back fat thickness and feed conversion efficiency. Protein turnover had very strong correlations with ribeye area and feed conversion efficiency. Average feed conversion efficiency in the current study was 0.17. To evaluate parameter estimates, the model was re-run using the new values for alpha and K2. On average, the model underpredicted final empty body weight by 0.08 kg and empty body fat percent by 0.01%-units. Considering the relatively large variation among observed alpha values and the magnitude of increase compared with those previously reported, further research is required to determine an accurate alpha.

P.41 Effect of cancer cachexia on muscle and total body protein turnover

P.41 Effect of cancer cachexia on muscle and total body protein turnover

Measurement of plasma leucine flux in rainbow trout (Salmo gairneri R.) using osmotic pump. Preliminary investigations on influence of diet

A method for the direct measurement of plasma amino acid flux, in rainbow trout, using the continuous infusion of L-[U-(14)C]-leucine with ALZET mini-osmotic pumps implanted into the peritoneal cavity, was developed. The fish were fed successively on three different diets (a commercial control diet, a semi-purified diet and a purified diet) during the 4 weeks of experiment. The amounts of radioactivity in the free pool and the protein of both the plasma and skin mucus were measured in these fish. The total flux of leucine was calculated either from the specific activity of leucine in the plasma (61.8 mg leucine. 100 g(-1).d(-1)) or from the amounts of labelled and unlabelled leucine flowing into the skin mucus protein (61.5 mg leucine. 100g(-1).day(-1)). The total plasma flux was not affected by changes in the diet. The contributions of total leucine oxidation and whole body protein turnover to plasma leucine flux (80% and 20% respectively) were estimated in fish fed the semi-purified diet.

Total-body protein turnover in parenterally fed neonates: effects of energy source studied by using [15N]glycine and [1-13C]leucine

The effects of nonprotein energy source (ie, glucose only vs glucose and lipid) on nitrogen retention and total-body protein turnover were studied in 20 parenterally fed newborn infants. All infants received approximately 3 g amino acids and 80-90 kcal.kg body wt.d. Total-body protein synthesis was estimated by using three constant-infusion, end-product methods: enrichment of urinary urea and ammonia in response to a [15N]glycine label and exhaled carbon dioxide enrichment in response to a [1-13C]leucine label. No differences were seen in nitrogen retention between the two energy sources. The estimate of total-body protein turnover obtained from the 13C label was similar to that obtained with the [15N]urea label. No differences in turnover rates were observed between the two diet groups. Use of the glucose-plus-lipid fuel system enhanced energy storage and the reutilization of amino acid for protein synthesis.

Effect of 2-mercaptoethanol on some metabolic indices of ageing of CBA/Ca inbred mice

It has been shown in several studies that 2-mercaptoethanol (2-ME) improves the life span and aspects of life performance of laboratory animals. To obtain further details on the beneficial effects of 2-ME, a long-term study has been performed on male CBA/Ca inbred mice treated with this antioxidant. Four month-old mice were each given 4 μg of 2-ME in physiological saline via intraperitoneal (i.p.) injection 3 × per week. Measurements were made of the following: cold tolerance (heat performance), apparent total body protein turnover ( T 1 2 ), changes in the major lipid and fatty acid compositions of the liver, superoxide dismutase activity and formation of malondialdehyde and observations on a range of pathological changes. It was found that the basal rectal temperatures of the treated mice were higher and in the oldest group, heat performance capacity was better than those of the controls. After about 1 year of age the apparent biological half-life time of total body protein ( T 1 2 ) was observed to be shorter in the treated mice. Significant increases were observed to occur in the proportions of the polyunsaturated fatty acids in the lipids of the liver in the mice injected with 2-ME. Although no differences were observed in the superoxide dismutase activities, malondialdehyde concentrations in the livers of the experimental mice were significantly increased. Autopsy data showed that Dunn-sarcomas associated with amyloidoses occurred more frequently in the untreated mice.

Dynamic aspects of whole-body nitrogen metabolism in uremic patients on dietary therapy.

15N-glycine administered orally to 3 patients with chronic renal failure and 15N-ammonium chloride given by intravenous infusion to 5 patients were used as tracers in studying the total body nitrogen metabolism during the course of dietary therapy. Patients on a diet providing 1.2 g protein per kilogram body weight per day had significantly lowered total nitrogen flux (Q) and rates of total body protein synthesis (S) and catabolism (C) as compared with the normal controls. A reduction in daily protein intake to 0.6 g/kg/day resulted in marked increases in all these parameters, so that the values actually approached that of the normal controls. While in the normal subjects low-protein intake did not affect the total body protein turnover significantly, it tended to decrease Q and to raise S, C, and S/Q. The results of the present study suggest that the adaptive response to restriction in protein intake is a more efficient utilization of nitrogen entering the metabolic pool for anabolic purposes, and less nitrogen excreted as urea. This response becomes manifest and essential to patients with chronic renal failure and forms the basis for low-protein diet therapy.

Simultaneous in vivo measurement of total body nitrogen by neutron-activation analysis and of protein turnover in humans and animals.

A knowledge of body protein content and turnover obtained by non-destructive analysis is of great value in many areas of clinical science and agriculture, concerned for example, with nutrition, growth and development. Measurement of nitrogen can be used as an indicator of protein and we describe what we believe to be some of the first simultaneous in vivo measurements of total body nitrogen and protein turnover in individuals and demonstrate that our techniques are suitable for sequential studies both in humans and animals as small as juvenile rats. In vivo neutron-activation analysis is used for total body nitrogen while mass-spectrometric measurement with a 15N-labelled amino acid tracer is used for protein turnover. Neutron activation is compared with a chemical method in animal carcasses.

Adaptation of body protein metabolism in adult and aging man

Aging causes a selective loss in lean body mass, muscle being most extensively eroded. This presentation is an analysis of the consequences of this age-related loss for protein and amino acid metabolism. The use of stable isotopes allows us to measure the dynamics of protein metabolism in the intact human subject, while the output of 3-methylhistidine permits estimates of muscle turnover to be made which show a smaller reduction in body protein turnover per kg body weight in elderly subjects. This is due to the reduced contribution by muscle protein turnover, which decreases from 30 per cent of total body protein turnover in the young adult to 20 per cent in the elderly, and can be entirely accounted for by the reduced mass of muscle, the rate of turnover per unit muscle weight being unchanged. The consequences of the changing proportions of major tissues with age has been examined for its impact on amino acid metabolism. The interaction of various organs in order to ensure metabolism of different amino acids is described. After a meal containing abundant protein, the liver selectively degraded the excess of most essential amino acids, while allowing the three branched-chain essential amino acids to pass through, so that in consequence they account for more than 50 per cent of the amino acid outflow from the splanchnic area. During this period of absorption muscle takes up amino acids, over 70 per cent being the branched-chain amino acids where they are catabolised, the nitrogen becoming available for formation of non-essential amino acids for muscle protein synthesis. The release of large amounts of glutamine from muscle is dependent on branched-chain amino acid degradation, whereas the relaese of large amounts of alanine is regulated by availability of pyruvate from glucose. The study of amino acid metabolism in elderly compared with young adults and its relationship to the declining mass of muscle with age is still in its initial stages. Metabolism of glycine at different levels of protein intake fails to demonstrate any significant effects of aging on metabolism of this amino acid. On the other hand, the flux of leucine shows a significant reduction in fasting elderly female subjects. This observation should be followed up by studying leucine kinetics following a meal of meat, in order to determine whether the reduced mass of muscle in the elderly will restrict the capacity to metabolise branched-chain amino acids. It has been concluded that the extensive age-related change in muscle mass should be explored for its impact on the nutritional requirements for branched-chain amino acids, their metabolism in health and disease, and their therapeutic uses at different ages.

Whole Body Protein Synthesis and Turnover in Normal Man and Malnourished Patients With and Without Known Cancer

Plateau enrichment of 15N-ammonia following 24 hour continuous intravenous infusion of 15N-glycine was used to measure total body protein turnover and synthesis in normal volunteers and malnourished patients, with and without cancer. The mean postabsorptive total body protein synthesis rate in three normal controls was 2.5 g protein/kg/day. Protein synthesis and turnover decreased by a mean of 23% following one week of fasting, and returned to baseline levels following one week of refeeding. In three malnourished patients without known tumor, whole body protein synthesis and turnover was similar to controls; following seven to ten days of total parenteral nutrition (TPN) in the nontumor-bearing patients whole body protein synthesis and turnover decreased by 18%. Three of seven malnourished patients with known tumors had marked elevations in total body protein synthesis and turnover; TPN increased protein turnover in five of seven patients with known cancer. This study suggests that some malignant tumors can increase whole body protein synthesis and turnover in both the malnourished and fed state. This increase in protein turnover may represent a direct effect of the tumor, or reflect concomitant illness.

Whole body protein synthesis and turnover in normal man and malnourished patients with and without known cancer.

Plateau enrichment of 15N-ammonia following 24 hour continuous intravenous infusion of 15N-glycine was used to measure total body protein turnover and synthesis in normal volunteers and malnourished patients, with and without cancer. The mean postabsorptive total body protein synthesis rate in three normal controls was 2.5 g protein/kg/day. Protein synthesis and turnover decreased by a mean of 23% following one week of fasting, and returned to baseline levels following one week of refeeding. In three malnourished patients without known tumor, whole body protein synthesis and turnover was similar to controls; following seven to ten days of total parenteral nutrition (TPN) in the nontumor-bearing patients whole body protein synthesis and turnover decreased by 18%. Three of seven malnourished patients with known tumors had marked elevations in total body protein synthesis and turnover; TPN increased protein turnover in five of seven patients with known cancer. This study suggests that some malignant tumors can increase whole body protein synthesis and turnover in both the malnourished and fed state. This increase in protein turnover may represent a direct effect of the tumor, or reflect concomitant illness.

Total body protein turnover and growth in children: Is it a futile cycle?

Rates of total body protein turnover during growth greatly exceed those necessary for net protein deposition. The excess protein synthesis would appear to be energy wasteful. However, a constant relationship is noted between whole body protein synthesis and basal energy needs, except during periods of rapid growth and development (newborn and adolescence). We suggest that whole body protein turnover is regulated by basal energy needs. The excess synthesis seen during periods of rapid growth is probably necessary to permit development and remodelling of tissues and organs to take place coincident with a mere increase in size.

Whole body protein turnover, studied with 15N-glycine, and muscle protein breakdown in mildly obese subjects during a protein-sparing diet and a brief total fast

A modification of the Picou and Taylor-Roberts Model was used to estimate rates of total body protein synthesis (S), breakdown (C), and amino nitrogen (N) flux (Q) in the metabolic N pool of five obese females. The subjects were fed egg white albumin at 1.5/kg ideal body weight (IBW) and total calories at 1.2 times the basal energy expenditure (fat:carbohydrate = 30%:50%) as a formula diet (period 1, 1 wk). This was followed by 3 wk during which the nonprotein calories were omitted (period 2, protein-sparing modified fast [PSMF]) and a 1-wk total fast (period 3). Estimates of body protein turnover and skeletal protein breakdown were made during the last 60 and 48 hr, respectively, of each period. Q, S, and C were 223 ± 22, 154 ± 22, and 150 ± 22 g protein 24 hr , respectively, for period 1. These values were unchanged at the end of period 2. Total fasting decreased Q and S by 36% and 27%, respectively ( p < 0.001), but C remained unchanged. Skeletal protein breakdown, as estimated by urinary Nτ-methylhistidine excretion, was 108 ± 47 μmole in period 1, 79 ± 51 μmole in period 2 ( p < 0.01), and 100 ± 49 μmole in period 3, representing 16 ± 5%, 12 ± 5% ( p < 0.01), and 16 ± 4% of whole body breakdown. N balance was unchanged in period 1 (−0.4 ± 1.2 g N) and the final week of period 2 (−0.4 ± 1.5 g N), but was −5.8 ± 0.6 g N in period 3. These data indicate that weight reduction with a PSMF is associated with a maintenance of total body protein turnover parameters and N balance but a reduction in skeletal protein breakdown, whereas a total fast causes a marked reduction in whole body protein synthesis and amino N flux with little change in the rate of total body and skeletal protein breakdown, resulting in a negative N balance. The minimization of N losses that develops after prolonged starvation is achieved at rates of whole body and skeletal protein breakdown similar to those found when the diet is adequate, suggesting that endogenous fat-derived fuels are as effective as exogenous energy in limiting protein catabolism. However, protein intake is necessary to maintain whole body protein synthesis under these conditions.

Influence of diabetes mellitus and insulin treatment on protein turnover in the rat

We studied the effects of diabetes mellitus and insulin treatment on total body protein synthesis and catabolism in the rat. Protein turnover was measured by infusing [ 15N]glycine intravenously and analyzing urine for [ 15N]urea enrichment. Diabetes mellitus was induced with streptozotocin (50 mg/kg), and diabetic animals were studied with and without insulin replacement. Normal animals, fed and starved, were studied as controls. Diabetes mellitus significantly decreased protein synthesis but did not change catabolism as compared with fed controls. Starvation of normal animals did not alter the protein synthesis rate but significantly increased the rate of protein catabolism. Insulin treatment restored the protein synthesis rate to normal while decreasing the rate of protein catabolism below normal. These findings for total body synthesis and catabolism are consistent with earlier studies of the effects of diabetes mellitus and insulin on protein metabolism in specific organs. It appears that the major effect of the diabetic state on total body protein turnover is to decrease synthesis without significantly changing catabolism.

Tissue enrichments and protein turnover measured with 15N-glycine.

VALUES for total body protein turnover (TBPT) measured in man using 15N-glycine1–3 are comparable with those obtained using 14C-amino acids4. Because 14C is radioactive it is of limited clinical use. The stable isotope 15N has a potentially wider application, although its use has been restricted for technical and conceptual reasons4. When a tracer labelled with 15N is used to measure TBPT the results are based on the enrichment of urea. This assumes that both urea and newly synthesised protein are derived from the same precursor N pool. Because urea is synthesised in the liver the enrichment of the precursor N pool for protein synthesis in the liver may determine the enrichment of urea. Thus the measurement of TBPT using 15N-glycine may be weighted heavily by the rate of hepatic protein turnover4,5. Similar problems may arise when urinary ammonia is the end product (M.H.N.G. and J. C. Waterlow, to be published). The extent of labelling of the precursor N pool is affected by at least two factors. First, after infusion of a 14C-amino acid, its specific radioactivity at plateau is lower in tissues than in plasma6–9, due to dilution with unlabelled amino acid derived from intracellular protein breakdown. This is termed internal recycling and also applies when 15N-glycine is infused. Second, when 15N-glycine is infused, extensive rapid intracellular transamination occurs especially in liver and kidney, so that the 15N is distributed to other amino acids, which will have a higher enrichment within the cell than in the plasma. Thus, depending on the balance between internal recycling and transamination, the intracellular enrichment of amino acids may be greater or less than the plasma enrichment. To investigate this problem we have infused 15N-glycine, and measured the enrichment of α-amino-N urea-N and ammonia-N in various tissues. The TBPT calculated from the liver urea-N enrichment gives a value which we consider representative and which agrees with published values based on 14C.

Measurement of muscle protein synthetic rate from serial muscle biopsies and total body protein turnover in man by continuous intravenous infusion of L-(alpha-15N)lysine.

1. Five healthy male subjects were studied by continuous infusion of L-[alpha-15N]lysine over 20-30 h with timed blood and urine samples, and two or three percutaneous needle biopsies of vastus lateralis muscle. 2. A standard creatine-free diet, quantitatively related to body surface area, was given for 5 days before the infusion. The [15N]lysine was administered at a constant rate in an amino acid solution with a nitrogen content of 0-96 mol/l, which constituted the sole source of exogenous nitrogen during the infusion. 3. A plateau level of plasma free [15N]lysine enrichment was achieved after infusion for 14 h. The total plasma lysine flux calculated from the plateau was 7-3 mmol/h (range 4-8-9-6). Total body protein turnover calculated from the lysine flux was 3-5 g day-1 kg body wt.-1 (range 2-5-5-0). 4. Muscle sarcoplasmic and myofibrillar fractions were separated, purified and the 15N enrichment was measured. The sarcoplasmic protein fractional synthetic rate was calculated as 3-8%/day (range 2-2-5-1). The myofibrillar protein synthetic rate was 1-46%/day (range 1-09-2-44). 5. Muscle mass, calculated from 24 h creatinine excretion, was 33-7 kg (range 28-8-37-4), which represented 50-0% of body weight (range 38-9-58-1). Total muscle protein synthesis was calculated to account for 53-2% (range 39-5-62-1) of total body protein syntehsis. 6. The advantages and limitations of using continuous infusion of [15N]lysine in human subjects are discussed.

Effects of heat, diet and hormones on total body protein turnover rate in young and old rats.

SummaryThe effects of diet restriction, thyroidectomy, adrenalectomy, and ambient temperature (28 and 34°) on protein turnover rate (K) were studied in young (47–49 days) and old (572–605 days) male rats. The data indicate that thyroidectomy decreased K under all treatments. Adrenalectomized rats supplemented with salt and 300 μg corticosterone every second day had a similar K and growth rate as the control rats. Exposure to heat and restriction of diet decreased K significantly only in the young rats. The effect of heat is suggested to be associated with the voluntary reduced feed intake as a result of hyperthermia and depressed appetite.

Total body protein turnover rate in rats: Effects of exogenous thyroxine and thyroidectomy

The effect of thyroxine (T 4) administration and thyroidectomy (Thx) on total body protein turnover rate was investigated in rats using the total body gamma activity of Se 75 labeled methionine. The results indicated that the daily injection of 2 ug of L-T 4 per 100 gm body wt significantly increased protein turnover rate. However, the injection of 4 ug of L-T 4 per 100 gm body wt produced no effect. The Thx rats showed a 32% decrease in protein turnover rate. The possible mechanisms in alteration of protein metabolism by absence or excess of T 4 are discussed.

A study of total body protein turnover in rats of different ages.

A study of total body protein turnover in rats of different ages.