Whole Body Protein Metabolism in Human Pulmonary Tuberculosis and Undernutrition: Evidence for Anabolic Block in Tuberculosis

1998 ◽  
Vol 94 (3) ◽  
pp. 321-331 ◽  
Author(s):  
Derek C. MacAllan ◽  
Margaret A. McNurlan ◽  
Anura V. Kurpad ◽  
George De Souza ◽  
Prakash S. Shetty ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Body Mass ◽  
Protein Metabolism ◽  
Protein Turnover ◽  
Nutrition Support ◽  
Whole Body ◽  
Body Protein ◽  
Leucine Kinetics ◽  
Body Energy ◽  
Net Protein

1. Differing patterns of protein metabolism are seen in wasting due to undernutrition and wasting due to chronic infection. 2. We investigated whole body energy and protein metabolism in nine subjects with pulmonary tuberculosis, six undernourished subjects (body mass index < 18.5 kg/m2) and seven control subjects from an Indian population. Fasting subjects were infused with l-[1-13C] leucine (2.3 μmol · h−1 · kg−1) for 8 h, 4 h fasted then 4 h fed. Leucine kinetics were derived from 13C-enrichment of leucine and α-ketoisocaproic acid in plasma and CO2 in breath. 3. Undernourished subjects, but not tuberculosis subjects, had higher rates of whole body protein turnover per unit lean body mass than controls [163.1 ± 9.4 and 148.6 ± 14.6 μmol compared with 142.8 ± 14.7 μmol leucine/h per kg, based on α-ketoisocaproic acid enrichment (P = 0.039)]. 4. In response to feeding, protein oxidation increased in all groups. Tuberculosis subjects had the highest fed rates of oxidation (47.0 ± 10.5 compared with 37.1 ± 5.4 μmol · h−1 · kg−1 in controls), resulting in a less positive net protein balance in the fed phase (controls, 39.7 ± 6.2; undernourished subjects, 29.2 ± 10.6; tuberculosis subjects, 24.5 ± 93; P = 0.010). Thus fed-phase tuberculosis subjects oxidized a greater proportion of leucine flux (33.2%) than either of the other groups (controls, 24.0%; undernourished subjects, 24.0%; P = 0.017). 5. Tuberculosis did not increase fasting whole body protein turnover but impaired the anabolic response to feeding compared with control and undernourished subjects. Such ‘anabolic block’ may contribute to wasting in tuberculosis and may represent the mechanism by which some inflammatory states remain refractory to nutrition support.

The Excretion of Isotope in Urea and Ammonia for Estimating Protein Turnover in Man with [15N]Glycine

1981 ◽  
Vol 61 (2) ◽  
pp. 217-228 ◽  
Author(s):  
E. B. Fern ◽  
P. J. Garlick ◽  
Margaret A. McNurlan ◽  
J. C. Waterlow
Keyword(s):  
Protein Metabolism ◽  
Protein Turnover ◽  
Mean Value ◽  
Intravenous Dose ◽  
Whole Body ◽  
Body Protein ◽  
End Products ◽  
The Mean ◽  
15N Urea ◽  
Normal Adults

1. Four normal adults were given [15N]-glycine in a single dose either orally or intravenously. Rates of whole-body protein turnover were estimated from the excretion of 15N in ammonia and in urea during the following 9 h. The rate derived from urea took account of the [15N]urea retained in body water. 2. In postabsorptive subjects the rates of protein synthesis given by ammonia were equal to those from urea, when the isotope was given orally, but lower when an intravenous dose was given. 3. In subjects receiving equal portions of food every 2 h rates of synthesis calculated from ammonia were much lower than those from urea whether an oral or intravenous isotope was given. Comparison of rates obtained during the post-absorptive and absorptive periods indicated regulation by food intake primarily of synthesis when measurements were made on urea, but regulation primarily of breakdown when measurements were made on ammonia. 4. These inconsistencies suggest that changes in protein metabolism might be assessed better by correlating results given by different end-products, and it is suggested that the mean value given by urea and ammonia will be useful for this purpose.

Resistance training reduces whole-body protein turnover and improves net protein retention in untrained young males

2006 ◽  
Vol 31 (5) ◽  
pp. 557-564 ◽  
Author(s):  
Joseph W. Hartman ◽  
Daniel R. Moore ◽  
Stuart M. Phillips
Keyword(s):  
Resistance Training ◽  
Resistance Exercise ◽  
Nitrogen Balance ◽  
Protein Turnover ◽  
Whole Body ◽  
Body Protein ◽  
Protein Retention ◽  
The Impact ◽  
Net Protein ◽  
Urinary Nitrogen

It is thought that resistance exercise results in an increased need for dietary protein; however, data also exists to support the opposite conclusion. The purpose of this study was to determine the impact of resistance exercise training on protein metabolism in novices with the hypothesis that resistance training would reduce protein turnover and improve whole-body protein retention. Healthy males (n = 8, 22 ± 1 y, BMI = 25.3 ± 1.8 kg·m–2) participated in a progressive whole-body split routine resistance-training program 5d/week for 12 weeks. Before (PRE) and after (POST) the training, oral [15N]-glycine ingestion was used to assess nitrogen flux (Q), protein synthesis (PS), protein breakdown (PB), and net protein balance (NPB = PS – PB). Macronutrient intake was controlled over a 5d period PRE and POST, while estimates of protein turnover and urinary nitrogen balance (Nbal = Nin – urine Nout) were conducted. Bench press and leg press increased 40% and 50%, respectively (p < 0.01). Fat- and bone-free mass (i.e., lean muscle mass) increased from PRE to POST (2.5 ± 0.8 kg, p < 0.05). Significant PRE to POST decreases (p <0.05) occurred in Q (0.9 ± 0.1 vs. 0.6 ± 0.1 g N·kg–1·d–1), PS (4.6 ± 0.7 vs. 2.9 ± 0.3 g·kg–1·d–1), and PB (4.3 ± 0.7 vs. 2.4 ± 0.2 g·kg–1·d–1). Significant training-induced increases in both NPB (PRE = 0.22 ± 0.13 g·kg–1·d–1; POST = 0.54 ± 0.08 g·kg–1·d–1) and urinary nitrogen balance (PRE = 2.8 ± 1.7 g N·d–1; POST = 6.5 ± 0.9 g N·d–1) were observed. A program of resistance training that induced significant muscle hypertrophy resulted in reductions of both whole-body PS and PB, but an improved NPB, which favoured the accretion of skeletal muscle protein. Urinary nitrogen balance increased after training. The reduction in PS and PB and a higher NPB in combination with an increased nitrogen balance after training suggest that dietary requirements for protein in novice resistance-trained athletes are not higher, but lower, after resistance training.

Effect of hyperinsulinemia on ovine fetal leucine kinetics during prolonged maternal fasting

1992 ◽  
Vol 263 (4) ◽  
pp. E696-E702 ◽  
Author(s):  
E. A. Liechty ◽  
D. W. Boyle ◽  
H. Moorehead ◽  
Y. M. Liu ◽  
S. C. Denne
Keyword(s):  
Protein Metabolism ◽  
Glucose Utilization ◽  
Whole Body ◽  
Postnatal Life ◽  
Body Protein ◽  
Leucine Oxidation ◽  
Leucine Kinetics ◽  
Ovine Fetus ◽  
Ovine Fetal

The primary effect of insulin on whole body protein metabolism in postnatal life is to reduce proteolysis. To assess the role of insulin in the regulation of protein metabolism in prenatal life, leucine kinetics were determined in the ovine fetus at baseline and in response to hyperinsulinemia. These measurements were made in each fetus in two different maternal states: ad libitum maternal feeding and after a 5-day maternal fast. Maternal fasting resulted in significant increases in baseline fetal leucine rate of appearance (Ra; 51.9 +/- 16.7 vs. 37.3 +/- 3.6 mumol/min, P < 0.05) and leucine oxidation (30.1 +/- 8.9 vs. 8.8 +/- 2.2 mumol/min, P < 0.05). Hyperinsulinemia, which was associated with significant increases in fetal glucose utilization, did not affect total fetal leucine R(a) or leucine release from fetal proteolysis in either maternal state. Under well-fed maternal conditions, hyperinsulinemia produced no changes in the fetal oxidative or nonoxidative disposal of leucine. In contrast, during maternal fasting, hyperinsulinemia reduced fetal leucine oxidation (11.0 +/- 3.7 vs. 31.1 +/- 8.9 mumol/min, P < 0.05) and increased the nonoxidative disposal of leucine (35.4 +/- 4.0 vs. 19.0 +/- 6.1 mumol/min, P < 0.05). This resulted in a change in the fetal leucine accretion rate from negative to positive (-20.9 +/- 7.5 vs. 7.5 +/- 6.7 mumol/min, P < 0.05). These results suggest that, under conditions of restricted maternal substrate intake, fetal hyperinsulinemia and the attendant increase in fetal glucose utilization are associated with increased protein synthesis rather than decreased protein breakdown, thereby improving fetal leucine carcass accretion.

scholarly journals Consumption of a Specially-Formulated Mixture of Essential Amino Acids Promotes Gain in Whole-Body Protein to a Greater Extent than a Complete Meal Replacement in Older Women with Heart Failure

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1360 ◽  
Author(s):  
Il-Young Kim ◽  
Sanghee Park ◽  
Ellen T. H. C. Smeets ◽  
Scott Schutzler ◽  
Gohar Azhar ◽  
...  
Keyword(s):  
Heart Failure ◽  
Amino Acids ◽  
Amino Acid ◽  
Body Mass ◽  
Essential Amino Acids ◽  
Whole Body ◽  
Meal Replacement ◽  
Anabolic Response ◽  
Body Protein ◽  
Net Protein

Heart failure in older individuals is normally associated with a high body mass index and relatively low lean body mass due to, in part, a resistance to the normal anabolic effect of dietary protein. In this study we have investigated the hypothesis that consumption of a specially-formulated composition of essential amino acids (HiEAAs) can overcome anabolic resistance in individuals with heart failure and stimulate the net gain of body protein to a greater extent than a commercially popular protein-based meal replacement beverage with greater caloric but lower essential amino acid (EAA) content (LoEAA). A randomized cross-over design was used. Protein kinetics were determined using primed continuous infusions of L-(2H5)phenylalanine and L-(2H2)tyrosine in the basal state and for four hours following consumption of either beverage. Both beverages induced positive net protein balance (i.e., anabolic response). However, the anabolic response was more than two times greater with the HiEAA than the LoEAA (p < 0.001), largely through a greater suppression of protein breakdown (p < 0.001). Net protein accretion (g) was also greater in the HiEAA when data were normalized for either amino acid or caloric content (p < 0.001). We conclude that a properly formulated EAA mixture can elicit a greater anabolic response in individuals with heart failure than a protein-based meal replacement. Since heart failure is often associated with obesity, the minimal caloric value of the HiEAA formulation is advantageous.

Chloroquine reduces whole body proteolysis in humans

1994 ◽  
Vol 267 (1) ◽  
pp. E183-E186 ◽  
Author(s):  
P. De Feo ◽  
E. Volpi ◽  
P. Lucidi ◽  
G. Cruciani ◽  
F. Santeusanio ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Turnover ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Body Protein ◽  
Leucine Kinetics ◽  
Lysosomal Proteolysis ◽  
Therapeutic Doses

The antimalaric drug chloroquine is a well known inhibitor of lysosomal proteolysis in vitro. The present study tests the hypothesis that therapeutic doses of the drug decrease proteolysis also in vivo in humans. Leucine kinetics were determined in 20 healthy volunteers given 12 and 1.5 h before the studies 250 and 500 mg, respectively, of chloroquine phosphate (n = 10) or similar tablets of placebo (n = 10). Chloroquine reduced the rates of leucine appearance, a measure of whole body proteolysis, from 2.45 +/- 0.08 to 2.19 +/- 0.08 mumol.kg-1.min-1 (P = 0.038) and those of nonoxidative leucine disposal, an estimate of whole body protein synthesis, from 2.16 +/- 0.08 to 1.95 +/- 0.06 mumol.kg-1.min-1 (P = 0.050). The drug resulted also in a marginally significant (P = 0.051) decrement in the plasma concentrations of glucose. The effects of chloroquine on protein turnover might be potentially useful in counteracting protein wasting complicating several catabolic diseases, whereas those on glucose metabolism can explain the sporadic occurrence of severe hypoglycemic episodes in malaria patients chronically treated with this drug.

Fasting and postprandial phenylalanine and leucine kinetics in liver cirrhosis

1994 ◽  
Vol 267 (1) ◽  
pp. E140-E149 ◽  
Author(s):  
P. Tessari ◽  
S. Inchiostro ◽  
R. Barazzoni ◽  
M. Zanetti ◽  
R. Orlando ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Protein Turnover ◽  
Normal Subjects ◽  
Whole Body ◽  
Protein Breakdown ◽  
Phenylalanine Concentration ◽  
Mixed Meal ◽  
Body Protein ◽  
Plasma Phenylalanine ◽  
Leucine Kinetics

To investigate body protein turnover and the pathogenesis of increased concentration of plasma phenylalanine in liver cirrhosis, we have studied phenylalanine and leucine kinetics in cirrhotic (diabetic and nondiabetic) patients, and in normal subjects, both in the postabsorptive state and during a mixed meal, using combined intravenous and oral isotope infusions. Postabsorptive phenylalanine concentration and whole body rate of appearance (Ra) were approximately 40% greater (P < 0.05) in patients than in controls. Leucine concentrations were comparable, but intracellular leucine Ra was also increased (P < 0.05), suggesting increased whole body protein breakdown. Postprandial phenylalanine Ra was also greater (P < 0.05) in the patients. This difference was due to a diminished fractional splanchnic uptake of the dietary phenylalanine (approximately 40% lower in the cirrhotics vs. controls, P < or = 0.05). Postprandial leucine Ra was also increased in the patients, but splanchnic uptake of dietary leucine was normal. Thus both increased body protein breakdown and decreased splanchnic extraction of dietary phenylalanine can account for the increased phenylalanine concentrations in liver cirrhosis.

Role of ovarian hormones in the regulation of protein metabolism in women: effects of menopausal status and hormone replacement therapy

2006 ◽  
Vol 291 (3) ◽  
pp. E639-E646 ◽  
Author(s):  
Michael J. Toth ◽  
Cynthia K. Sites ◽  
Dwight E. Matthews
Keyword(s):  
Postmenopausal Women ◽  
Protein Metabolism ◽  
Protein Turnover ◽  
Hormone Replacement ◽  
Menopausal Status ◽  
Ovarian Hormones ◽  
Hormone Deficiency ◽  
Whole Body ◽  
Protein Breakdown ◽  
Body Protein

The age-related decline in fat-free mass is accelerated in women after menopause, implying that ovarian hormone deficiency may have catabolic effects on lean tissue. Because fat-free tissue mass is largely determined by its protein content, alterations in ovarian hormones would likely exert regulatory control through effects on protein balance. To address the hypothesis that ovarian hormones regulate protein metabolism, we examined the effect of menopausal status and hormone replacement therapy (HRT) on protein turnover. Whole body protein breakdown, oxidation, and synthesis were measured under postabsorptive conditions using [13C]leucine in healthy premenopausal ( n = 15, 49 ± 1 yr) and postmenopausal ( n = 18, 53 ± 1 yr) women. In postmenopausal women, whole body protein turnover and plasma albumin synthesis rates (assessed using [13C]leucine and [2H]phenylalanine) were also measured following 2 mo of treatment with oral HRT (0.625 mg conjugated estrogens + 2.5 mg medroxyprogesterone acetate, n = 9) or placebo ( n = 9). No differences in whole body protein breakdown, oxidation, or synthesis were found between premenopausal and postmenopausal women. Protein metabolism remained similar between groups after statistical adjustment for differences in adiposity and when subgroups of women matched for percent body fat were compared. In postmenopausal women, no effect of HRT was found on whole body protein breakdown, synthesis, or oxidation. In contrast, our results support a stimulatory effect of HRT on albumin fractional synthesis rate, although this did not translate into alterations in circulating albumin concentrations. In conclusion, our results suggest no detrimental effect of ovarian hormone deficiency coincident with the postmenopausal state, and no salutary effect of hormone repletion with HRT, on rates of whole body protein turnover, although oral HRT regimens may increase the synthesis rates of albumin.

Leucine kinetics in endurance-trained humans

1990 ◽  
Vol 69 (1) ◽  
pp. 1-6 ◽  
Author(s):  
L. S. Lamont ◽  
D. G. Patel ◽  
S. C. Kalhan
Keyword(s):  
Energy Expenditure ◽  
Protein Turnover ◽  
Resting Energy Expenditure ◽  
Whole Body ◽  
Body Protein ◽  
Energy Expenditures ◽  
Leucine Kinetics ◽  
Constant Rate ◽  
Tracer Dilution ◽  
Resting Energy

This study compared whole-body leucine kinetics in endurance-trained (TRN) and sedentary (SED) control subjects. Eleven men and women (6 TRN, 5 SED) underwent a 6-h primed, constant-rate infusion of L-[1-13C]leucine. Leucine turnover and oxidation were measured using tracer dilution and by measuring 13C enrichment of expired CO2 combined with respiratory calorimetry. Whole-body leucine turnover was greater in the TRN subjects (P less than 0.004; TRN 98.3 +/- 5.0, SED 75.3 +/- 4.2 mumol.kg-1.h-1; mean +/- SE), but there was no difference between groups in leucine oxidation (TRN 13.1 +/- 0.97, SED 11.5 +/- 0.48 mumol.kg-1.h-1). Thus more leucine turnover was available for nonoxidative utilization. In addition, the TRN subjects had higher resting energy expenditures compared with the SED group, and when all subjects were included in the analysis, there was a significant correlation between energy expenditure and protein turnover (n = 11, R = 0.61, P = 0.05). Therefore the heightened resting energy expenditure in the TRN subjects may be accounted for by an increased whole-body protein turnover. These results suggest that endurance training results in increased leucine and/or protein turnover, which may contribute to the increased resting energy expenditure observed in these subjects.

Relationship of maternal protein turnover and lean body mass during pregnancy and birth length

2001 ◽  
Vol 101 (1) ◽  
pp. 65-72 ◽  
Author(s):  
Sarah L. DUGGLEBY ◽  
Alan A. JACKSON
Keyword(s):  
Body Composition ◽  
Lean Body Mass ◽  
Body Mass ◽  
Protein Turnover ◽  
Adult Life ◽  
Birth Length ◽  
Whole Body ◽  
Body Protein ◽  
Increased Risk ◽  
Size At Birth

Epidemiological evidence shows that small size at birth is associated with an increased risk of developing cardiovascular and metabolic disease in adult life. We have examined the relationships between size at birth and maternal body composition and protein turnover in normal pregnant women. A group of 27 multiparous Caucasian women with singleton pregnancies were studied at around 18 and 28 weeks' gestation. Body composition was determined by anthropometry, and whole-body protein turnover was estimated by using a single oral dose of [15N]glycine and the end-product method. The baby's weight and length were measured within 48 h of birth. Mothers with a greater lean body mass had higher rates of protein turnover at 18 weeks' gestation. This association was largely accounted for by differences in the mother's visceral, rather than muscle, mass. Mothers who had higher protein turnover at 18 weeks' gestation had babies that were longer at birth. After adjustment for the duration of gestation and the baby's sex, 26% of the variation in length at birth was accounted for by maternal protein synthesis at 18 weeks' gestation. Maternal protein intake was not associated with the baby's birth length. Thus the mother's ability to nourish her fetus is influenced by her body composition and her rate of protein turnover. Dietary intake does not adequately characterize this ability.

Aspects of protein metabolism after elective surgery in patients receiving constant nutritional support

1990 ◽  
Vol 78 (6) ◽  
pp. 621-628 ◽  
Author(s):  
F. Carli ◽  
J. Webster ◽  
V. Ramachandra ◽  
M. Pearson ◽  
M. Read ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Metabolic Rate ◽  
Protein Metabolism ◽  
Protein Turnover ◽  
Resting Metabolic Rate ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Body Protein ◽  
Urinary Nitrogen

1. The present study was designed in an attempt to resolve conflicting views currently in the literature relating to the effect of surgery on various aspects of protein metabolism. 2. Sequential post-operative (2, 4 and 6 days) changes in whole-body protein turnover, forearm arteriovenous difference of plasma amino acids, glucose, lactate and free fatty acids, muscle concentration of free amino acids, RNA and protein, urinary nitrogen and 3-methylhistidine, plasma concentrations of insulin, cortisol and growth hormone, and resting metabolic rate, were measured in six patients undergoing uncomplicated elective total abdominal hysterectomy. 3. All patients received a constant daily diet, either orally or intravenously, based on 0.1 g of nitrogen/kg and an energy content of 1.1 times the resting metabolic rate for 7 days before and 6 days after surgery. 4. Whole-body protein turnover, synthesis and breakdown increased significantly 2 days after surgery (P <0.05) and returned towards pre-operative levels thereafter. 5. Forearm release of branched-chain amino acids and alanine, and efflux of glucose and lactate, were enhanced 4 days after surgery (P <0.05). Muscle glutamine and alanine concentrations were decreased on the fourth and sixth days after surgery (P <0.05). The RNA/protein ratio (indicating the capacity for protein synthesis) was unaltered. 6. A significant increase in urinary nitrogen and 3-methylhistidine was observed on days 3 and 4 after surgery (P <0.05). Thereafter, these parameters remained elevated, although failing to reach statistical significance. 7. The resting metabolic rate was significantly increased (P <0.05) 2 days after surgery but the respiratory quotient (0.77) was unchanged. 8. These data support the contention that whole-body protein synthesis and breakdown increase after surgery. Differences observed pre- and post-operatively between leucine kinetic estimates and other methods of quantifying protein metabolism indicate that only like methodologies should be compared.

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