Dynamic aspects of whole body glycine metabolism: Influence of protein intake in young adult and elderly males

The influence of adult age and adequacy of dietary protein intake on whole body glycine metabolism was studied in human subjects. Five healthy young adult males (19–25 yr) and six elderly males (64–78 yr) were given an adequate-protein diet (1.5 g protein/kg/day) for 7 days and a low-protein diet (0.4 g protein/kg/day) for 14 days. At the end of each dietary period, whole body glycine flux and rates of glycine synthesis were estimated with the use of a continuous 60 hr oral administration of ¹⁵N-glycine and determination of ¹⁵N enrichment of plasma glycine by gas chromatography-mass spectrometry with selected ion monitoring. Mean whole body glycine flux and the rate of endogenous glycine synthesis were 458 and 351 μmole/kg body weight/hr, respectively, for young adults receiving the diet adequate in protein; similar values were obtained in the elderly group. Feeding the diet low in protein resulted in an extensive and significant reduction in both parameters in young adults and also in elderly subjects to a similar extent. Measurement of ¹⁵N enrichment in plasma serine gave a constant ratio of ¹⁵n enrichment in plasma free serine relative to glycine for both age groups and at the two protein intake levels. It is concluded that aging of adults has little impact on the quantitative aspects of whole body glycine metabolism, but that it responds extensively to changes in protein intake. Thus, it appears that glycine synthesis and flux are integrated with the body's total nitrogen metabolism and requirement for dietary nitrogen.     

Whole-body protein synthesis and breakdown rates in children before and after reconstructive surgery of the skin.

The effects of minor surgery on dynamic aspects of whole-body nitrogen metabolism were explored in healthy children aged 4--15 yr. A continuous administration of 15N-glycine was used to estimate rates of whole-body protein synthesis and breakdown both before reconstructive surgery of the skin and 5 days afterward. Mean preoperative values for protein synthesis and protein breakdown were 3.9 and 3.4 g protein/kg body weight/day, respectively. Protein synthesis decreased by 15% (p less than 0.05) postoperatively, but body weight, intake of protein and calories, nitrogen balance, and protein breakdown did not differ significantly between the two periods. Protein synthetic rate correlated (p less than 0.05) with protein (r = +0.75) and calorie (r = +0.58) intake. These results indicate that minor surgery causes a small decrease in the rate of whole-body protein synthesis even though calorie and nitrogen balance are maintained.     

The influence of intravenous nutrition on protein dynamics following surgery

Rates of whole body protein turnover were measured in 13 adult patients one day following abdominal surgery. A constant intravenous infusion of L-(1-¹⁴C)-leucine was used to estimate rates of whole body protein flux, synthesis, breakdown and fractional synthesis rates of albumin and mixed globulins. After a baseline measurement when saline was infused, patients were assigned to one of three groups in order to assess the relative effects of three hypocaloric intravenous nutrition regimens upon these rates. Group A (n = 5) was given 108 g/day of crystalline L-amino acids. Group D (n = 4) received 216 g/day of glucose and 22 units of insulin/day. Group AD (n = 4) received a combination of the two regimens (108 g/day amino acids, 216 g/day glucose and 22 units insulin/day). The two isotope infusion studies lasted 20 hr after which the specific intravenous diet was continued for a total of three days. The amino acid infusion increased whole body protein flux from 3.07 g/kg ideal body weight · day to 4.56 g/kg ideal body weight · day (p < 0.05), amino acid oxidation from 0.59 g/kg ideal body weight · day to 1.82 g/kg ideal body weight · day (p < 0.05) and improved protein balance from −0.59 g/kg ideal body weight · day to −0.12 g/kg ideal body weight · day (p < 0.05). Plasma globulin synthesis was also increased from 19.2%/day to 36.0%/day (p < 0.05). In contrast, glucose and insulin infusions reduced amino acid oxidation from 0.54 g/kg ideal body weight · day to 0.35 g/kg ideal body weight · day (p < 0.05) by decreasing the rate of protein breakdown (from 3.09 g/kg ideal body weight · day to 2.55 g/kg ideal body weight · day). Both globulin and albumin synthesis were also reduced from 26.1%/day to 18.8%/day (p < 0.05) and 7.5%/day to 4.2%/day (p < 0.05), respectively. The combined regimen of amino acids, glucose and insulin produced the greatest improvement in protein balance from −0.42 g/kg ideal body weight · day to +0.83 g/kg ideal body weight · day (p < 0.05) through a reduction in protein breakdown and an increase in protein synthesis. However, plasma protein synthesis was not significantly affected. Amino acid oxidation rates were positively correlated to the rate of nitrogen excretion in the urine when dietary intake was constant (r = 0.84, p < 0.01). Further significant correlations were observed between whole body protein flux and body weight (r = 0.70), amino acid intake and whole body protein synthesis (r = 0.82), flux and amino acid oxidation (r = 0.60), flux and globulin (r = 0.65) and albumin synthesis (r = 0.54) and finally, oxidation and globulin synthesis (r = 0.69). The positive correlations observed between protein flux and whole body and plasma protein synthesis suggest that increased amino acid availability promotes whole body and plasma protein synthesis. Protein synthesis is supported in postoperative patients by amino acid containing infusions and suppressed by solutions containing only glucose and insulin.     

Whole body leucine and lysine metabolism studied with [1-13C]leucine and [α-15N]lysine: Response in healthy young men given excess energy intake

An excess intake of dietary energy in adult subjects enhances body N balance but the mechanism(s) responsible remains unknown. Thus, dynamic aspects of metabolism of whole body leucine and lysine were explored in healthy young adult men, receiving adequate or excess energy intakes, using a primed, continuous intravenous infusion of a mixture of L-[¹³C]leucine and L-[α-¹⁵N]lysine to provide a constant enrichment of plasma free leucine and lysine over a period of 2 hr. Twelve subjects were studied with the labeled amino acids following an overnight fast (post-absorptive state) and 12 additional subjects while consuming small isocaloric, isonitrogenous horly meals (fed state). Preceding each infusion, subjects were adapted for 7 days to experimental diets, providing a constant and barely adequate protein intake of 0.6 g/kg body weight/day, at either a maintenance energy intake, determining from estimates of usual food intake that maintain body weight, or an energy intake 25% greater than the maintenance level. The excess non-protein energy intake was given as an isocaloric mixture of carbohydrate and fat (eight subjects) or entirely as either carbohydrate or fat (eight subjects each). Whole body leucine and lysine flux remained unchanged with excess energy intakes, regardless of the source of energy substrate. Based on the combined data with all energy intake sources, the rate of leucine oxidation was significantly reduced and the rate of leucine incorporation into body protein showed a small increase with excess energy intakes. Thus, when expressed as net protein gain (leucine incorporation into body protein minus leucine release from protein breakdown) a significantly greater rate of body protein retention occurred with excess energy intake and this was more marked for the high carbohydrate diets. Mean change in body leucine retention determined by ¹³C-leucine was in good agreement with that calculated from alterations in overall N balance. In addition, the rate of inflow of leucine and of lysine into the metabolic pool via tissue protein breakdown was reduced with ingestion of meals. These results indicate that excess energy intake improves overall body N balance by reducing amino acid oxidation and enhancing protein synthesis. Furthermore, these effects are particularly evident at a time when passage of amino acids to tissues is stimulated by ingestion and absorption of meals.     

Albumin synthesis in young and elderly subjects using a new stable isotope methodology: Response to level of protein intake

Albumin synthesis was evaluated in 5 young adult males (19–25 yr) and 6 elderly males (64–78 yr) by a procedure involving oral administration of ¹⁵N-glycine every 3 hr over a 60-hr period. From about 40 hr onwards, urinary urea achieved a plateau of ¹⁵N-enrichment, which was estimated from the average of the last five (low protein) or seven (adequate protein) consecutive three-hourly urinary samples of the 60-hr period. This enrichment plateau was used as an index of the ¹⁵N-enrichment of the guanidine N of hepatic free arginine. The ¹⁵N-enrichment of the guanidine N of arginine in serum albumin was determined and albumin synthesis was estimated by comparing this value with the estimated enrichment of precursor hepatic arginine. Using this methodology, serum albumin concentration, synthesis, rate and plasma volume were measured when the young and elderly subjects had received an adequate protein intake (1.5 g · kg^?1 for 7 days) or a low protein intake (0.4 g · kg^?1 for 14 days). Serum albumin concentration was lower in the elderly at both levels of protein intake; protein intake did not affect this parameter in either age-group. Plasma volume (per kg body weight) did not differ between young and old, but increased in both groups when they were given the low-protein diet, so that the total intravascular albumin mass increased in both age groups significantly in the case of the young, and was probably due to net transfer of albumin from the extravascular pool. The fractional synthesis rate of the whole body albumin pool with adequate intake of protein was 4.0%/day in the young and 3.4%/day in the elderly. This fractional rate was reduced significantly by giving the low-protein diet to the young subjects, but was not reduced in the elderly. Absolute synthesis rates, calculated per kg body weight and per kg body cell mass, led to a similar conclusion. Whole body protein synthesis was also estimated from urinary ¹⁵N-urea enrichment using the Picou and Taylor-Roberts model. Albumin synthesis as a percentage of whole body protein synthesis (5%–6%) was reduced in the young adults by giving the low-protein diet, but was unchanged in the elderly. In conclusion, the rate of albumin synthesis in the young, but not in the elderly, is sensitive to changes in protein intake. It is suggested that albumin synthesis in the elderly is controlled at a lower set point, which prevents its response to higher protein intakes.     

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 $\text{150 ± 22 g protein}\text{24 hr}$, 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.     

Urinary excretion of 3-methylhistidine as an index of muscle protein catabolism in postoperative trauma: The effect of parenteral nutrition

The effect of different intravenous nutritional regimens on nitrogen balance and 3-methylhistidine (3-MeHIS) excretion were studied during a 6-day period following major elective surgery in 28 patients. All patients were kept on a synthetic diet 4 days prior to surgery and were given 0.1 g amino acid N and 120 kJ/kg . day. Postoperatively, all patients received parenteral nutrition with approximately 170 kJ/kg . day. Postoperatively, all patients received parenteral nutrition with approximately 170 kJ/kg . day. Three groups of patients were given varying amounts and proportions of amino acids while in one group no amino acids were administered. Preoperatively, urinary 3-MeHIS excretion (determined by a newly developed automatic analyzer) was 240.3 mumole/day +/- 9.2, nitrogen balance was -1.8 g N +/- 0.19. Postoperatively, nitrogen balance was less negative when amino acids were given. The degree of improvement depended on the amount, but not on the composition of nitrogen administered. In all four groups, 3-MeHIS outputs were elevated when compared with preoperative excretion. The 3-MeHIS excretion (mumole/day) was increased more in patients on high amino acid supply than in patients with low or no nitrogen supply. In each of the groups the 3-MeHIS excretion was negatively correlated to the nitrogen balance. Regression analyses suggest that postoperative muscle protein breakdown occurs in relation to the body protein loss. Amino acid administration seems not to decrease muscle protein breakdown, but rather, appears to stimulate protein synthesis, resulting in less net protein loss. The mean rate of muscle protein breakdown in the postoperative state was estimated to be 80 g/day, assuming 4.2 mumole 3-MeHIS per g mixed human muscle protein. This exceeded the mean preoperative breakdown by about 23 g muscle protein per day. This increase might be due to the metabolic response to the trauma and also in part to tissue damage by the surgical procedure.     

Dietary control of protein turnover

The balance between protein synthesis and breakdown (protein turnover) regulates whole-body protein mass. The relationships between dietary changes (amount and composition of food) and protein synthesis, protein breakdown and amino acid oxidation have been explored in order to better understand adaptations of protein and amino acid metabolism. Methods for measuring protein synthesis, especially whole-body protein synthesis, can be divided into two groups: the 15N end-product method (urea and/or ammonia), and the incorporation of labelled amino acid(s) into proteins. Assumptions and limitations of the widely used two-pool model (free amino acid and protein pools) are discussed. Results obtained with different methods and for amino acids have been compared, to assess their ability to detect changes in protein synthesis rates. Methods of measuring protein breakdown have also been described briefly. Food intake affects whole-body and tissue protein turnover throughout development of animals and humans in different ways. Protein metabolism fluctuates during the 24-hour period in response to intermittent food intake. During the post-prandial period, a net whole-body protein deposition occurs. This is essentially due to increased protein synthesis. The free amino acid pool and amino acid oxidation rates also increase. Consequently, amino acids are used to a great extent as energy substrates. In contrast, a decrease in protein breakdown could enhance protein deposition. During fasting, the rates of whole-body protein synthesis are lower than those of protein breakdown. This results in protein loss, essentially because the drop in protein synthesis rate in muscle is pronounced. N balance is controlled by the amounts and composition of the diet and by changes in protein synthesis and breakdown. Increasing food intake above levels of energy equilibrium can produce growth by enhancing both the whole-body protein synthesis and breakdown rates. Below energy equilibrium, whole-body protein loss occurs because of decreased protein synthesis which becomes lower than protein breakdown. Protein synthesis rate is the main factor controlling N balance in response to alterations in food intake. Increasing dietary protein, especially the essential amino acids, involves increased rates of whole-body protein synthesis and breakdown. The improved N balance obtained by enhancing dietary non-protein energy (carbohydrate, fat) can be brought on by reducing amino acid oxidation and slightly increasing protein synthesis. The effects of dietary protein and energy on protein turnover are apparently additive.     

A model for determination of total body protein synthesis based upon compartmental analysis of the plasma [15N] glycine decay curve

A model for whole body glycine nitrogen flux based on the compartmental analysis of plasma [¹⁵N] glycine decay curves is described and used for the measurements of (1) total body glycine nitrogen flux and the components of this flux in three healthy young adults and (2) total body protein synthesis based on the conversion of ¹⁵N to excretory products, ie, the sum of urinary [¹⁵N] urea and ¹⁵NH₃ and the amount of labeled urea remaining in the body at five hours following administration of [¹⁵N] glycine. The mean glycine nitrogen flux was 3.93 ± 0.42 mg N · kg^?1 · h^?1 (SEM). The major components of this flux are de novo synthesis of glycine, which accounts for 18% to 27%, and release from protein breakdown, which accounts for 62% to 73%. The outward pathways of glycine from the total body free glycine pool are conversion to other amino acids and oxidation to excretory end products (30% to 42%) and incorporation into protein, which accounts for 45% to 61% of glycine N loss from the metabolic pool. The mean rate of total body protein synthesis as determined by compartmental analysis was 3.56 g protein · kg^?1 · day^?1. The results that were obtained for protein synthesis and whole body glycine kinetics accord well with previous studies in normal adults, using the stochastic model.     

Fasting metabolism in infants. I. Effect of severe undernutrition on energy and protein utilization.

Fasting energy metabolism was studied in infants to determine the rates of utilization of endogenous carbohydrate, fat, and protein in relation to length of fasting, glucose homeostasis, other circulating energy substrates and hormones, and severe depletion of energy reserves due to prior malnutrition. Five subjects about 1 yr of age were each studied before and after restoration of their energy reserves. Following 3 days of a standard maintenance intake of energy and protein, the subjects were fasted until glycogen oxidation became negligible. Total energy utilization, determined by hourly oxygen consumption, did not diminish as a result of fasting but was significantly less when malnourished than when recovered, 66 versus 79 kcal/kg/day. In all cases the major energy source shifted from oxidation of dietary carbohydrate and glycogen to oxidation of fat, determined from the respiratory quotient, until the oxidation of glycogen became negligible and fat provided 94% of energy in the malnourished subjects after 21 hr and 92% in the recovered subjects after 27 hr. Utilization of protein, determined from urinary nitrogen excretion, remained very low in the malnourished infants accounting for a maximum of 4% of energy, 103 mg N/kg/day, whereas after recovery, protein utilization doubled as a result of fasting, finally accounting for 7% of energy, 226 mg N/kg/day (p less than 0.005). Urea accounted for 60% of total urinary N in both groups and plasma urea increased correspondingly in the recovered but not in the malnourished subjects. Plasma glucose decreased to about 40 mg/100 ml in both groups as glycogen oxidation diminished. The maximum amount of glucose that could have been derived from dietary carbohydrate, glycogen, glycerol, and amino acids decreased over this time from about 6 to 1 mg/kg/min. Alanine declined in relation to glucose concentration and was not different in the two groups in spite of the difference in urea production. Glycerol free fatty acids, beta-hydroxybutyrate, and acetoacetate increased in both groups, but the latter three of these remained significantly less in the malnourished group. Insulin decreased rapidly and remained equally low in both groups. Urinary epinephrine increased in both groups and cortisol was elevated after fasting, while growth hormone did not increase significantly. It is concluded that fasting infants complete the transition from dietary carbohydrate to endogenous fat as the major energy source much faster than do adults, proportionate to relatively greater energy utilization. Severe wasting did not prevent energy homeostasis in spite of greatly depleted body fat. Oxidation of fat continued to provide virtually all of the fasting energy requirements, although ketosis was relatively less. Utilization of endogenous protein also increased as a result of fasting but, by contrast, provided only a very small fraction of total energy, and this was substantially diminished as a result of wasting, similar to what has been found in starved adults...     

Effects of an increase in protein intake on hepatic efficacy for urea synthesis in healthy subjects and in patients with cirrhosis

The efficacy of urea synthesis as measured by functional hepatic nitrogen clearance (i.e., the relation of urea synthesis rate to blood alpha-amino nitrogen concentration) was studied before and after diet protein supplementation in six healthy subjects and five patients with stable cirrhosis (galactose elimination capacity about 60% of control). Daily protein intake was increased for 14 days by a protein-enriched liquid from (mean +/- S.D.) 1.01 +/- 0.32 g/kg body wt. to 1.62 +/- 0.31 g/kg body wt in the control subjects, and from 0.69 +/- 0.21 g/kg body wt. to 1.50 +/- 0.15 g/kg body wt. in the patients with cirrhosis. This increased the hepatic nitrogen clearance from 27 +/- 10 l/h to 39 +/- 15 l/h in the control subjects (p less than 0.05) and from 15 +/- 6 l/h to 21 +/- 7 l/h in the cirrhosis patients (p less than 0.05). There was no effect on the galactose elimination capacity in any group. Compared to the control subjects, the response in hepatic nitrogen clearance relative to the increase in protein intake was reduced by 60% in the patients. Basal glucagon was 75% higher in the patients and increased by 50% during high protein intake (p less than 0.05), but did not parallel the increase in hepatic nitrogen clearance, and it did not change in the control subjects. The study shows that an increase in protein intake selectively increases liver function with regard to disposal of amino nitrogen; the mechanism is qualitatively intact but quantitatively deficient in patients with cirrhosis of the liver, and does not seem to depend on glucagon.     

Effect of tyrosine intake on the rate of phenylalanine hydroxylation in adult males

This study evaluated the effect of varying levels of tyrosine intake on the estimation of phenylalanine hydroxylation. Healthy men were fed 1 g protein kg(-1) x d(-1) for a 2-day period. On the third day, subjects consumed a formula diet containing 1 g protein kg(-1) x d(-1) hourly over 10 hours, and primed hourly oral doses of L-[15N]phenylalanine and L-[3,3-2H2]tyrosine for the last 6 hours. Each subject was studied at 7 levels of tyrosine intake (3.0, 4.5, 6.0, 7.5, 9.0, 10.5, and 12.0 mg x kg(-1) x d(-1)) at a constant intake of phenylalanine (9 mg x kg(-1) x d(-1), 4.55 micromol x kg(-1) x h(-1)). Phenylalanine hydroxylation was estimated from the ratio of plasma amino acid isotope enrichment of [15N]phenylalanine and [15N]tyrosine and the tyrosine flux estimated from [2H2]tyrosine enrichment. Phenylalanine and tyrosine fluxes showed no significant response to alterations in the intake of tyrosine. Linear regression analysis showed a significant response such that the rate of phenylalanine hydroxylation decreased as tyrosine intake increased (R2 = .21; P = .003). The mean rates of phenylalanine hydroxylation were 3.89 to 8.06 micromol x kg(-1) x h(-1). Given model uncertainties, the apparent protein breakdown observed at tyrosine intake levels less than 10.5 mg x kg(-1) x d(-1), and the significant differences observed between the present data and our prior data, we cannot estimate the tyrosine requirement with any degree of certainty with the present hydroxylation results.     

Effects of moderate physical training on prednisone-induced protein wasting: a study of whole-body and bone protein metabolism

This study investigated the possibility of preventing prednisone-induced protein wasting by regular physical activity. Eight healthy untrained volunteers took prednisone (30 mg/d for nine days), once after a 4-week exercise program that consisted of jogging 2.5 miles four times a week, and once without exercise. Whole body protein turnover was measured from the 15N enrichment plateau of urinary ammonia during ingestion of 15N glycine at hourly intervals. Whole-body protein synthesis and breakdown were derived from nitrogen flux, nitrogen intake, and urinary nitrogen elimination. Muscle myofibrillar protein breakdown was explored by measuring urinary 3-methylhistidine excretion. Bone protein metabolism was studied by measuring serum bone GLA protein (BGP), a specific marker of bone protein synthesis, and urinary elimination of hydroxyproline, an index of bone resorption. Whole-body protein turnover was significantly increased by exercise and prednisone (+19% and +17%, respectively); this effect was related to increased protein synthesis during exercise training (+27%, P less than .01) and to increased protein breakdown during prednisone administration without exercise (+21%, P less than .05). In contrast, values of protein turnover, synthesis, and breakdown were not different from control when the subjects took prednisone after training. Urinary excretion of 3-methylhistidine was decreased (-15%, P less than .05) at the end of the prednisone administration period but was identical to the control value when the subjects took prednisone in association with exercise. In contrast, serum BGP was significantly decreased by prednisone, with or without exercise (-35%, P less than .001). These data suggest that moderate exercise training can prevent, at least in part, the protein loss induced by prednisone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sterol balance in abetalipoproteinemia: studies in a patient with homozygous familial hypobetalipoproteinemia.

A new case of homozygous familial hypobetalipoproteinemia is reported in a 16-yr-old girl. Apoprotein B was absent from plasma and the patient had acanthocytes and steatorrhea, but minimal neurologic dysfunction. Total body cholesterol synthesis was assessed intermittently over a 30-mo period by sterol balance techniques. The rate of synthesis of cholesterol was higher (15.0 +/- 2.9 mg/kg/day) in the patient (8.3 +/- 0.4 mg/kg/day than in 3 control children, p less than 0.005). Bile acid synthesis was similar (4.6 +/- 1.8 versus 4.0 +/- 1.7 mg/kg/day) in the patient and controls, but total body sterol synthesis was significantly higher (19.6 +/- 3.0 versus 12.2 +/- 2.0, p less than 0.005). The absorption of orally administered [1,2,(3)H] cholesterol in the patient was low and less than 0.5% of the label appeared in the total plasma volume at all times up to 48 hr. Estimates of the extent that malabsorption of biliary cholesterol contributes to the enhanced excretion of neutral sterols in this case indicate that all of the increase can be explained on this basis. Thus, although the mechanisms for the increased sterol synthesis in this case may relate to the absence of chylomicrons and low density lipoproteins in plasma, the magnitude of the increase can be fully explained on the basis of a compensatory mechanism to maintain cholesterol homeostasis in the face of enhanced fecal losses.     

Quantitative contribution by skeletal muscle to elevated rates of whole-body protein breakdown in burned children as measured by Nτ-methylhistidine output

To investigate the distribution of whole-body protein breakdown in children suffering from severe burn injury, the rates of skeletal muscle and whole-body protein breakdown were estimated in a total of 13 studies on 7 children, ages 4–13 yr, with body burns ranging from 36% to 83% of body surface area. Results were compared with values reported for healthy children. Whole-body protein breakdown was determined using ¹⁵N-glycine, and muslcle protein breakdown was estimated from measurements of urinary excretion of N^τ-methylhistidine. The children were receiving a flesh-free diet, free of exogenous N^τ-methylhistidine. The mean rate of whole-body protein breakdown was 5.7 ± 1.3 g protein/kg/day, which was higher than that found previously in healthy children of the same age group. The mean rate of N^τ-methylhistidine excretion was 4.3 μmoles/kg/day, or 205 μmoles/g creatinine; this was higher than the rate for healthy children as determined by interpolation of data reported in the literature. Estimating the rate of muscle protein breakdown from these data revealed that skeletal muscle accounts for 19.1% ± 7.6% of whole-body protein breakdown in burned children. When compared with published data for healthy subjects of varying ages, the present findings suggest that, although the rate of muscle protein breakdown is elevated in children recovering from burn injury, its percentage contribution to the rate of whole-body protein breakdown, also elevated in response to burn injury, remains within approximately normal limits.     

Rates of whole body protein synthesis and breakdown increase with the severity of inflammatory bowel disease

Rates of whole body protein synthesis and breakdown were estimated in 19 undernourished patients with inflammatory bowel disease from the cumulative nine hour excretion of urinary 15NH3 after intravenous injection of 15N glycine. Thirty six studies were made during constant nutrient input either parenterally by 3 litre bag technique (29 studies), or enterally by nasogastric infusion of protein containing liquid feeds (four studies), or by diet kitchen prepared food eaten at two hourly intervals (three studies). Mean daily intakes were 50.7 kcal and 0.29 g nitrogen/kg body weight. Synthesis and break down rates correlated significantly with disease activity as judged by erythrocyte sedimentation rate and by ranking by an observer unaware of the turnover results. Rates for synthesis and breakdown by this method were about 2.1 and 1.7 g protein/kg/24 h respectively for ESR 10 increasing to 4.0 and 3.3 for ESR 100.     

Effect of reduced dietary intake on energy expenditure, protein turnover, and glucose cycling in man

The effect of a 50% reduction in food intake on energy expenditure, protein metabolism, glucose cycling, and body composition was investigated in eight moderately overweight men. The prestudy mean calorie and protein intake was determined for eight subjects. They were then maintained on this diet for 6 weeks (mean +/- SEM, 3,269 +/- 75 kcal/d, 20.0 +/- 0.5 g N/d, period I), after which the diet was reduced uniformly in the major foodstuffs by 50% for the next 4 weeks (1,555 +/- 38 kcal/d, 9.6 +/- 5 g N/d, period II). At the end of each period we measured (1) body fat and fat free mass by underwater weighing, (2) 24-hour energy expenditure by indirect calorimetry in a calorimeter, (3) whole body protein synthesis and breakdown rates with 15N glycine, and (4) glucose cycling between glucose and glucose-6-phosphate and fructose cycling between fructose-6-phosphate and fructose-1,6 bisphosphate with 6,6-D2- and 2-D1-labeled glucose. The results were subjects lost 4.0 +/- 0.1 kg fat (by underwater weighing) during the 4 weeks on the reduced-energy regimen. Protein turnover and glucose cycling were reduced by 20% and 15%, respectively. Twenty-four-hour energy expenditure was 2,553 +/- 166 kcal/d for period I and 2,369 +/- 69 kcal/d for period II, giving a difference of 184 +/- 34 kcal/d between the two periods. In conclusion, (1) although energy intake was reduced by 50%, the decrease in energy expenditure was small due to the buffering effect of body fat.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nutrition as a determinant of blood rheology and fibrinogen in athletes

Blood rheology is influenced by metabolism and nutrition. We investigated this issue in 41 elite athletes exercising 13+/-0.9 hr/wk (mean age: 23.9+/-0.67 yr; mean VO2max: 52.6+/-2.3 ml/min/kg body weight) with a standardised nutritional questionnaire suitable for sports medicine. Calorie intake (% of recommended intake) was negatively correlated with the RBC disaggregability threshold (r=-0.505, p=0.01). There were negative correlations between fibrinogen and protein intake (% of the total caloric intake r=-0.787, p=0.0008; amount in g/kg/day r=-0.597, p=0.03). Accordingly, the RBC disaggregability threshold was also correlated negatively with protein intake (r=-0.508, p=0.05). Lipid intake (g/kg/day) was negatively correlated with the RBC disaggregability threshold (r=-0.564, p=0.03) and positively to the hematocrit/viscosity ratio (r=0.531, p=0.03). Carbohydrate intake (g/kg/day) was positively correlated with whole blood viscosity (r=0.517, p=0.04) and negatively to the hematocrit/viscosity ratio (r=-0.4863, p=0.05). In addition fibrinogen was negatively correlated with hematocrit (r=-0.4129, p=0.036) and positively with a host of aggregation parameters (p<0.001). Therefore fibrinogen levels and red cell rheology exhibit correlations with the nutritional status in athletes. Low protein intake appears to be associated with (mildly) raised fibrinogen and aggregability, and low calorie intake is associated with lower RBC disaggregability.     

In vivo demonstration of nitrogen-sparing mechanisms for glucose and amino acids in the injured rat

Changes in protein metabolism 8 hr after anesthesia and femur fracture were studied in healthy rats fasted or receiving either intravenous glucose or crystalline amino acids. Whole body rates of amino acid turnover (flux) and release from protein (breakdown) as well as fractional synthetic rates of mixed muscle, liver, and plasma protein were measured using the constant infusion of L-(I-¹⁴C)-leucine. Injury resulted in a 24% and 63% increase in the synthesis of liver (p < 0.05) and plasma proteins (p < 0.01), respectively. Amino acid infusions in the injured animals further increased the synthesis of liver protein (from 36.6% to 44.3%/day, p < 0.05) and increased muscle protein synthesis (from 7.0% to 9.3%/day, p < 0.05) without altering rates of protein breakdown. Glucose infusions, in contrast, reduced whole body protein breakdown 36% (p < 0.05) when compared to fasting, and depleted the plasma essential amino acid pool (p < 0.05). The usual increases in liver protein synthesis observed in fasted rats following injury were not seen when the animals were receiving intravenous glucose. The nitrogen-sparing mechanism of these two infusions are different. Protein-free glucose infusions impair the normal response to injury aimed at increasing visceral protein synthesis and maintaining plasma essential amino acid concentrations.     

Protein Content in Diabetes Nutrition Plan

Medical nutrition therapy plays a major role in diabetes management. Macronutrient composition has been debated for a long time. However, there is increasing evidence that a modest increase in dietary protein intake above the current recommendation is a valid option toward better diabetes control, weight reduction, and improvement in blood pressure, lipid profile, and markers of inflammation. Increasing the absolute protein intake to 1.5–2 g/kg (or 20–30% of total caloric intake) during weight reduction has been suggested for overweight and obese patients with type 2 diabetes and normal kidney function. Increased protein intake does not increase plasma glucose, but increases the insulin response and results in a significant reduction in hemoglobin A_1c. In addition, a higher dietary protein intake reduces hunger, improves satiety, increases thermogenesis, and limits lean muscle mass loss during weight reduction using a reduced calorie diet and increased physical activity. It is preferable to calculate protein intake for patients with diabetes as grams per kilogram of body weight and not as a fixed percentage of total energy intake to avoid protein malnutrition when a hypocaloric diet is used. The relationship between protein intake as grams per kilogram of body weight and albumin excretion rate is very weak, except in hypertensive patients and particularly in those with uncontrolled diabetes. A protein intake of 0.8–1 g/kg should be recommended only for patients with diabetes and chronic kidney disease. Other patients with diabetes should not reduce protein intake to less than 1 g/kg of body weight. This review discusses the effects of different amounts of protein intake in a diabetes meal plan. It particular, it discusses the effects of protein intake on renal function, the effects of protein content on diabetes control, and the effects of increased dietary protein on body weight.