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

Alanine and glutamine constitute the two most important nitrogen carriers released from the muscle. We studied the intracellular amino acid transport kinetics and protein turnover in nine end-stage renal disease (ESRD) patients and eight controls by use of stable isotopes of phenylalanine, alanine, and glutamine. The amino acid transport kinetics and protein turnover were calculated with a three-pool model from the amino acid concentrations and enrichment in the artery, vein, and muscle compartments. Muscle protein breakdown was more than synthesis (nmol·min−1·100 ml leg−1) during hemodialysis (HD) (169.8 ± 20.0 vs. 125.9 ± 21.8, P < 0.05) and in controls (126.9 ± 6.9 vs. 98.4 ± 7.5, P < 0.05), but synthesis and catabolism were comparable pre-HD (100.7 ± 15.7 vs. 103.4 ± 14.8). Whole body protein catabolism decreased by 15% during HD. The intracellular appearance of alanine (399.0 ± 47.1 vs. 243.0 ± 34.689) and glutamine (369.7 ± 40.6 vs. 235.6 ± 27.5) from muscle protein breakdown increased during dialysis (nmol·min−1·100 ml leg−1, P < 0.01). However, the de novo synthesis of alanine (3,468.9 ± 572.2 vs. 3,140.5 ± 467.7) and glutamine (1,751.4 ± 82.6 vs. 1,782.2 ± 86.4) did not change significantly intradialysis (nmol·min−1·100 ml leg−1). Branched-chain amino acid catabolism (191.8 ± 63.4 vs. −59.1 ± 42.9) and nonprotein glutamate disposal (347.0 ± 46.3 vs. 222.3 ± 43.6) increased intradialysis compared with pre-HD (nmol·min−1·100 ml leg−1, P < 0.01). The mRNA levels of glutamine synthase (1.45 ± 0.14 vs. 0.33 ± 0.08, P < 0.001) and branched-chain keto acid dehydrogenase-E2 (3.86 ± 0.48 vs. 2.14 ± 0.27, P < 0.05) in the muscle increased during HD. Thus intracellular concentrations of alanine and glutamine are maintained during HD by augmented release of the amino acids from muscle protein catabolism. Although muscle protein breakdown increased intradialysis, the whole body protein catabolism decreased, suggesting central utilization of amino acids released from skeletal muscle.

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Muscle wasting in emphysema

Clinical Science ◽

10.1042/cs0750415 ◽

1988 ◽

Vol 75 (4) ◽

pp. 415-420 ◽

Cited By ~ 73

Author(s):

W. L. Morrison ◽

J. N. A. Gibson ◽

C. Scrimgeour ◽

M. J. Rennie

Keyword(s):

Protein Synthesis ◽

Protein Turnover ◽

Muscle Wasting ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Myofibrillar Protein ◽

Whole Body ◽

Protein Breakdown ◽

Body Protein ◽

Net Protein

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

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Whole body and forearm substrate metabolism in hyperthyroidism: evidence of increased basal muscle protein breakdown

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00253.2004 ◽

2005 ◽

Vol 288 (6) ◽

pp. E1067-E1073 ◽

Cited By ~ 32

Author(s):

Anne Lene Dalkjær Riis ◽

Jens Otto Lunde Jørgensen ◽

Signe Gjedde ◽

Helene Nørrelund ◽

Anne Grethe Jurik ◽

...

Keyword(s):

Amino Acid ◽

Muscle Protein ◽

Clinical Manifestations ◽

Metabolic Effects ◽

Whole Body ◽

Synthesis Rate ◽

Protein Synthesis Rate ◽

Protein Breakdown ◽

Body Protein ◽

Muscle Protein Breakdown

Thyroid hormones have significant metabolic effects, and muscle wasting and weakness are prominent clinical features of chronic hyperthyroidism. To assess the underlying mechanisms, we examined seven hyperthyroid women with Graves' disease before (Ht) and after (Eut) medical treatment and seven control subjects (Ctr). All subjects underwent a 3-h study in the postabsorptive state. After regional catheterization, protein dynamics of the whole body and of the forearm muscles were measured by amino acid tracer dilution technique using [15N]phenylalanine and [2H4]tyrosine. Before treatment, triiodothyronine was elevated (6.6 nmol/l) and whole body protein breakdown was icreased 40%. The net forearm release of phenylalanine was increased in hyperthyroidism (μg·100 ml−1·min−1): −7.0 ± 1.2 Ht vs. −3.8 ± 0.8 Eut ( P = 0.04), −4.2 ± 0.3 Ctr ( P = 0.048). Muscle protein breakdown, assessed by phenylalanine rate of appearance, was increased (μg·100 ml−1·min−1): 15.5 ± 2.0 Ht vs. 9.6 ± 1.4 Eut ( P = 0.03), 9.9 ± 0.6 Ctr ( P = 0.02). Muscle protein synthesis rate did not differ significantly. Muscle mass and muscle function were decreased 10–20% before treatment. All abnormalities were normalized after therapy. In conclusion, our results show that hyperthyroidism is associated with increased muscle amino acid release resulting from increased muscle protein breakdown. These abnormalities can explain the clinical manifestations of sarcopenia and myopathy.

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280 THE EFFECTS OF POSTNATAL AGE ON THE WHOLE BODY PROTEIN METABOLISM AND SKELETAL MUSCLE PROTEIN BREAKDOWN OF PREMATURE INFANTS

Pediatric Research ◽

10.1203/00006450-198104001-00291 ◽

1981 ◽

Vol 15 ◽

pp. 486-486

Author(s):

P Pencharz ◽

M Masson ◽

F Desgranges ◽

A Papageorgiou

Keyword(s):

Skeletal Muscle ◽

Premature Infants ◽

Protein Metabolism ◽

Muscle Protein ◽

Whole Body ◽

Protein Breakdown ◽

Skeletal Muscle Protein ◽

Body Protein ◽

Muscle Protein Breakdown

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Total-Body Protein Turnover in Human Premature Neonates: Effects of Birth Weight, Intra-Uterine Nutritional Status and Diet

Clinical Science ◽

10.1042/cs0610207 ◽

1981 ◽

Vol 61 (2) ◽

pp. 207-215 ◽

Cited By ~ 46

Author(s):

P. B. Pencharz ◽

M. Masson ◽

F. Desgranges ◽

A. Papageorgiou

Keyword(s):

Skeletal Muscle ◽

Birth Weight ◽

Muscle Protein ◽

Whole Body ◽

Protein Breakdown ◽

Skeletal Muscle Protein ◽

Nitrogen Flux ◽

Body Protein ◽

Muscle Protein Breakdown ◽

Total Body

1. The effects of birth weight, intra-uterine nutritional status and protein and energy intake on whole-body protein turnover, and skeletal muscle protein breakdown were examined in 40 premature infants. 2. Total-body nitrogen flux was 26% higher in the small-for-gestational-age compared with appropriate-for-gestation-age infants; similarly, whole-body protein synthesis and breakdown were increased by 26 and 35% respectively (P < 0.01). 3. The lower-birth-weight neonates (< 1500 g) had higher rates of skeletal muscle protein breakdown; 1.23 ± 1.12 g day−1 kg−1, as compared with 0.54 ± 0.28 g for the high-birth-weight group (P < 0.05). 4. Protein intake was inversely correlated with the fraction of nitrogen flux coming from endogenous protein breakdown (P < 0.05) and with skeletal muscle protein breakdown (P < 0.05). There were no significant relationships found between energy intake and the parameters of protein metabolism. 5. On the basis of the turnover data, evidence is presented that the protein requirements for milk-protein fed premature neonates is less than 4.3 g day−1 kg−1.

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Muscle Protein Synthesis and Whole-Body Protein Turnover Responses to Ingesting Essential Amino Acids, Intact Protein, and Protein-Containing Mixed Meals with Considerations for Energy Deficit

Nutrients ◽

10.3390/nu12082457 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2457 ◽

Cited By ~ 3

Author(s):

Jess A. Gwin ◽

David D. Church ◽

Robert R. Wolfe ◽

Arny A. Ferrando ◽

Stefan M. Pasiakos

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Protein Turnover ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Energy Deficit ◽

Whole Body ◽

Intact Protein ◽

Body Protein ◽

Protein Feeding

Protein intake recommendations to optimally stimulate muscle protein synthesis (MPS) are derived from dose-response studies examining the stimulatory effects of isolated intact proteins (e.g., whey, egg) on MPS in healthy individuals during energy balance. Those recommendations may not be adequate during periods of physiological stress, specifically the catabolic stress induced by energy deficit. Providing supplemental intact protein (20–25 g whey protein, 0.25–0.3 g protein/kg per meal) during strenuous military operations that elicit severe energy deficit does not stimulate MPS-associated anabolic signaling or attenuate lean mass loss. This occurs likely because a greater proportion of the dietary amino acids consumed are targeted for energy-yielding pathways, whole-body protein synthesis, and other whole-body essential amino acid (EAA)-requiring processes than the proportion targeted for MPS. Protein feeding formats that provide sufficient energy to offset whole-body energy and protein-requiring demands during energy deficit and leverage EAA content, digestion, and absorption kinetics may optimize MPS under these conditions. Understanding the effects of protein feeding format-driven alterations in EAA availability and subsequent changes in MPS and whole-body protein turnover is required to design feeding strategies that mitigate the catabolic effects of energy deficit. In this manuscript, we review the effects, advantages, disadvantages, and knowledge gaps pertaining to supplemental free-form EAA, intact protein, and protein-containing mixed meal ingestion on MPS. We discuss the fundamental role of whole-body protein balance and highlight the importance of comprehensively assessing whole-body and muscle protein kinetics when evaluating the anabolic potential of varying protein feeding formats during energy deficit.

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Differential regulation of lipid and protein metabolism in obese vs. lean subjects before and after a 72-h fast

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00464.2015 ◽

2016 ◽

Vol 311 (1) ◽

pp. E224-E235 ◽

Cited By ~ 21

Author(s):

Ann Mosegaard Bak ◽

Andreas Buch Møller ◽

Mikkel Holm Vendelbo ◽

Thomas Svava Nielsen ◽

Rikke Viggers ◽

...

Keyword(s):

Amino Acid ◽

Fat Mass ◽

Muscle Protein ◽

Whole Body ◽

Mrna Levels ◽

Mass Unit ◽

Body Protein ◽

Protein Levels ◽

Tracer Techniques ◽

Obese Subjects

Increased availability of lipids may conserve muscle protein during catabolic stress. Our study was designed to define 1) intracellular mechanisms leading to increased lipolysis and 2) whether this scenario is associated with decreased amino acid and urea fluxes, and decreased muscle amino acid release in obese subjects under basal and fasting conditions. We therefore studied nine lean and nine obese subjects twice, after 12 and 72 h of fasting, using measurements of mRNA and protein expression and phosphorylation of lipolytic and protein metabolic signaling molecules in fat and muscle together with whole body and forearm tracer techniques. Obese subjects displayed increased whole body lipolysis, decreased urea production rates, and decreased forearm muscle protein breakdown per 100 ml of forearm tissue, differences that persisted after 72 h of fasting. Lipolysis per fat mass unit was reduced in obese subjects and, correspondingly, adipose tissue hormone-sensitive lipase (HSL) phosphorylation and mRNA and protein levels of the adipose triglyceride lipase (ATGL) coactivator CGI58 were decreased. Fasting resulted in higher HSL phosphorylations and lower protein levels of the ATGL inhibitor G0S2. Muscle protein expressions of mammalian target of rapamycin (mTOR) and 4EBP1 were lower in obese subjects, and MuRf1 mRNA was higher with fasting in lean but not obese subjects. Phosphorylation and signaling of mTOR decreased with fasting in both groups, whereas ULK1 protein and mRNA levels increased. In summary, obese subjects exhibit increased lipolysis due to a large fat mass with blunted prolipolytic signaling, together with decreased urea and amino acid fluxes both in the basal and 72-h fasted state; this is compatible with preservation of muscle and whole body protein.

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Prolonged bed rest decreases skeletal muscle and whole body protein synthesis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.270.4.e627 ◽

1996 ◽

Vol 270 (4) ◽

pp. E627-E633 ◽

Cited By ~ 118

Author(s):

A. A. Ferrando ◽

H. W. Lane ◽

C. A. Stuart ◽

J. Davis-Street ◽

R. R. Wolfe

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Bed Rest ◽

Whole Body ◽

Protein Breakdown ◽

Skeletal Muscle Protein ◽

Model Calculations ◽

Body Protein

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

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Fasting and postprandial phenylalanine and leucine kinetics in liver cirrhosis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1994.267.1.e140 ◽

1994 ◽

Vol 267 (1) ◽

pp. E140-E149 ◽

Cited By ~ 9

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.

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Measurement of muscle protein degradation in live mice by accumulation of bestatin-induced peptides

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1997.273.6.e1149 ◽

1997 ◽

Vol 273 (6) ◽

pp. E1149-E1157 ◽

Cited By ~ 3

Author(s):

Violeta Botbol ◽

Oscar A. Scornik

Keyword(s):

Protein Degradation ◽

Protein Turnover ◽

Skeletal Muscles ◽

Muscle Protein ◽

Cellular Proteins ◽

Protein Breakdown ◽

Maximum Accumulation ◽

Muscle Protein Breakdown ◽

Muscle Protein Degradation ◽

Acute Changes

Bestatin, an aminopeptidase inhibitor, permits the degradation of cellular proteins to di- and tripeptides but interferes with the further breakdown of these peptides to amino acids. We propose to measure instant rates of protein degradation in skeletal muscles of intact mice by the accumulation of bestatin-induced intermediates. Muscle protein was labeled by injection ofl-[guanidino-14C]arginine; 3 days later, maximum accumulation of intermediates was measured in abdominal wall muscles 10 min after the intravenous injection of 5 mg of bestatin. The peptides were partially purified and hydrolyzed in 6 N HCl, and the radioactivity in peptide-derived arginine was determined, after conversion to14CO2by treatment with arginase and urease. The measurement of bestatin-induced intermediates provides a unique tool for studying acute changes in muscle protein turnover in live mice. We observed a 62% increase in muscle protein breakdown after a 16-h fast, which was reversed by refeeding for 3.5 h, and a 38% increase after 3 days of protein depletion.

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