Contribution of skeletal muscle protein in elevated rates of whole body protein catabolism in trauma patients

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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Growth Hormone and Insulin Reverse Net Whole Body and Skeletal Muscle Protein Catabolism in Cancer Patients

Annals of Surgery ◽

10.1097/00000658-199209000-00007 ◽

1992 ◽

Vol 216 (3) ◽

pp. 280-290 ◽

Cited By ~ 54

Author(s):

RONALD F. WOLF ◽

DAVID B. PEARLSTONE ◽

ELLIOT NEWMAN ◽

MARTIN J. HESLIN ◽

AMNON GONENNE ◽

...

Keyword(s):

Skeletal Muscle ◽

Growth Hormone ◽

Cancer Patients ◽

Muscle Protein ◽

Whole Body ◽

Protein Catabolism ◽

Skeletal Muscle Protein

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Skeletal muscle degradation and nitrogen wasting in rats with chronic metabolic acidosis

Clinical Science ◽

10.1042/cs0800457 ◽

1991 ◽

Vol 80 (5) ◽

pp. 457-462 ◽

Cited By ~ 38

Author(s):

Bryan Williams ◽

Ellis Layward ◽

John Walls

Keyword(s):

Skeletal Muscle ◽

Metabolic Acidosis ◽

Time Course ◽

Muscle Protein ◽

Nitrogen Excretion ◽

Protein Catabolism ◽

Skeletal Muscle Protein ◽

Body Protein ◽

Chronic Metabolic Acidosis ◽

Urea Production

1. Chronic metabolic acidosis is associated with impaired growth and negative nitrogen balance, suggesting that it promotes endogenous protein catabolism. 2. Skeletal muscle is the major repository of body protein and is a potential target for stimuli of protein catabolism. 3. This study in vivo examines the effects of chronic metabolic acidosis on the relationship between growth, nitrogen disposal and skeletal muscle catabolism in the rat. 4. Growth, nitrogen utilization and acquisition of body mass were significantly impaired in acidotic animals compared with pair-fed controls. 5. Total nitrogen excretion was significantly increased in acidotic rats despite decreased urea production. The time course of this response to acidosis was synchronous with that of accelerated protein catabolism in skeletal muscle. 6. It is proposed that metabolic acidosis impairs growth by stimulating skeletal muscle protein catabolism. It is suggested that this forms part of a co-ordinated multi-organ homoeostatic response to acidosis, skeletal muscle and down-regulated urea production supplying the nitrogen required for renal ammoniagenesis.

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Effect of glycogen availability on human skeletal muscle protein turnover during exercise and recovery

Journal of Applied Physiology ◽

10.1152/japplphysiol.00108.2009 ◽

2010 ◽

Vol 109 (2) ◽

pp. 431-438 ◽

Cited By ~ 63

Author(s):

Krista R. Howarth ◽

Stuart M. Phillips ◽

Maureen J. MacDonald ◽

Douglas Richards ◽

Natalie A. Moreau ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Protein Turnover ◽

Muscle Protein ◽

Whole Body ◽

Skeletal Muscle Protein ◽

Protein Balance ◽

Body Protein ◽

Muscle Protein Turnover ◽

Net Protein

We examined the effect of carbohydrate (CHO) availability on whole body and skeletal muscle protein utilization at rest, during exercise, and during recovery in humans. Six men cycled at ∼75% peak O2 uptake (V̇o2peak) to exhaustion to reduce body CHO stores and then consumed either a high-CHO (H-CHO; 71 ± 3% CHO) or low-CHO (L-CHO; 11 ± 1% CHO) diet for 2 days before the trial in random order. After each dietary intervention, subjects received a primed constant infusion of [1-13C]leucine and l-[ring-2H5]phenylalanine for measurements of the whole body net protein balance and skeletal muscle protein turnover. Muscle, breath, and arterial and venous blood samples were obtained at rest, during 2 h of two-legged kicking exercise at ∼45% of kicking V̇o2peak, and during 1 h of recovery. Biopsy samples confirmed that the muscle glycogen concentration was lower in the L-CHO group versus the H-CHO group at rest, after exercise, and after recovery. The net leg protein balance was decreased in the L-CHO group compared with at rest and compared with the H-CHO condition, which was primarily due to an increase in protein degradation (area under the curve of the phenylalanine rate of appearance: 1,331 ± 162 μmol in the L-CHO group vs. 786 ± 51 μmol in the H-CHO group, P < 0.05) but also due to a decrease in protein synthesis late in exercise. There were no changes during exercise in the rate of appearance compared with rest in the H-CHO group. Whole body leucine oxidation increased above rest in the L-CHO group only and was higher than in the H-CHO group. The whole body net protein balance was reduced in the L-CHO group, largely due to a decrease in whole body protein synthesis. These data extend previous findings by others and demonstrate, using contemporary stable isotope methodology, that CHO availability influences the rates of skeletal muscle and whole body protein synthesis, degradation, and net balance during prolonged exercise in humans.

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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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Release of skeletal muscle peptide fragments identifies individual proteins degraded during insulin deprivation in type 1 diabetic humans and mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00175.2016 ◽

2016 ◽

Vol 311 (3) ◽

pp. E628-E637 ◽

Cited By ~ 11

Author(s):

Matthew M. Robinson ◽

Surendra Dasari ◽

Helen Karakelides ◽

H. Robert Bergen ◽

K. Sreekumaran Nair

Keyword(s):

Skeletal Muscle ◽

Protein Degradation ◽

High Resolution Mass Spectrometry ◽

Degradation Products ◽

Muscle Protein ◽

Whole Body ◽

Peptide Fragments ◽

Skeletal Muscle Protein ◽

Body Protein

Insulin regulates skeletal muscle protein degradation, but the types of proteins being degraded in vivo remain to be determined due to methodological limitations. We present a method to assess the types of skeletal muscle proteins that are degraded by extracting their degradation products as low-molecular weight (LMW) peptides from muscle samples. High-resolution mass spectrometry was used to identify the original intact proteins that generated the LMW peptides, which we validated in rodents and then applied to humans. We deprived insulin from insulin-treated streptozotocin (STZ) diabetic mice for 6 and 96 h and for 8 h in type 1 diabetic humans (T1D) for comparison with insulin-treated conditions. Protein degradation was measured using activation of autophagy and proteasome pathways, stable isotope tracers, and LMW approaches. In mice, insulin deprivation activated proteasome pathways and autophagy in muscle homogenates and isolated mitochondria. Reproducibility analysis of LMW extracts revealed that ∼80% of proteins were detected consistently. As expected, insulin deprivation increased whole body protein turnover in T1D. Individual protein degradation increased with insulin deprivation, including those involved in mitochondrial function, proteome homeostasis, nDNA support, and contractile/cytoskeleton. Individual mitochondrial proteins that generated more LMW fragment with insulin deprivation included ATP synthase subunit-γ (+0.5-fold, P = 0.007) and cytochrome c oxidase subunit 6 (+0.305-fold, P = 0.03). In conclusion, identifying LMW peptide fragments offers an approach to determine the degradation of individual proteins. Insulin deprivation increases degradation of select proteins and provides insight into the regulatory role of insulin in maintaining proteome homeostasis, especially of mitochondria.

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Measuring Protein Turnover in the Field: Implications for Military Research

Advances in Nutrition ◽

10.1093/advances/nmaa123 ◽

2020 ◽

Author(s):

Katrina L Hinde ◽

Thomas J O'Leary ◽

Julie P Greeves ◽

Sophie L Wardle

Keyword(s):

Skeletal Muscle ◽

Protein Turnover ◽

Muscle Protein ◽

Military Training ◽

Field Research ◽

Whole Body ◽

Skeletal Muscle Protein ◽

Free Living ◽

Body Protein ◽

Product Method

ABSTRACT Protein turnover reflects the continual synthesis and breakdown of body proteins, and can be measured at a whole-body (i.e. aggregated across all body proteins) or tissue (e.g. skeletal muscle only) level using stable isotope methods. Evaluating protein turnover in free-living environments, such as military training, can help inform protein requirements. We undertook a narrative review of published literature with the aim of reviewing the suitability of, and advancements in, stable isotope methods for measuring protein turnover in field research. The 2 primary approaches for measuring protein turnover are based on precursor- and end-product methods. The precursor method is the gold-standard for measuring acute (over several hours) skeletal muscle protein turnover, whereas the end-product method measures chronic (over several weeks) skeletal muscle protein turnover and provides the opportunity to monitor free-living activities. Both methods require invasive procedures such as the infusion of amino acid tracers and muscle biopsies to assess the uptake of the tracer into tissue. However, the end-product method can also be used to measure acute (over 9–24 h) whole-body protein turnover noninvasively by ingesting 15N-glycine, or equivalent isotope tracers, and collecting urine samples. The end-product method using 15N-glycine is a practical method for measuring whole-body protein turnover in the field over short (24 h) time frames and has been used effectively in recent military field research. Application of this method may improve our understanding of protein kinetics during conditions of high physiological stress in free-living environments such as military training.

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Leucine incorporation into mixed skeletal muscle protein in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1988.254.2.e208 ◽

1988 ◽

Vol 254 (2) ◽

pp. E208-E213 ◽

Cited By ~ 32

Author(s):

K. S. Nair ◽

D. Halliday ◽

R. C. Griggs

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Fiber Type ◽

Whole Body ◽

Synthesis Rate ◽

Protein Synthesis Rate ◽

Skeletal Muscle Protein ◽

Body Protein

Fractional mixed skeletal muscle protein synthesis (FMPS) was estimated in 10 postabsorptive healthy men by determining the increment in the abundance of [13C]-leucine in quadriceps muscle protein during an intravenous infusion of L-[1-13C]leucine. FMPS in our subjects was 0.046 +/- 0.003%/h. Whole-body muscle protein synthesis (MPS) was calculated based on the estimation of muscle mass from creatinine excretion and compared with whole-body protein synthesis (WBPS) calculated from the nonoxidative portion of leucine flux. A significant correlation (r2 = 0.73, P less than 0.05) was found between MPS (44.7 +/- 3.4 mg.kg-1.h-1) and WBPS (167.8 +/- 8.5 mg.kg-1.h-1). The contribution of MPS to WBPS was 27 +/- 1%, which is comparable to the reports in other species. Morphometric analyses of adjacent muscle samples in eight subjects demonstrated that the biopsy specimens consisted of 86.5 +/- 2% muscular as opposed to other tissues. Because fiber type composition varies between biopsies, we examined the relationship between proportions of each fiber type and FMPS. Variation in the composition of biopsies and in fiber-type proportion did not affect the estimation of muscle protein synthesis rate. We conclude that stable isotope techniques using serial needle biopsies permit the direct measurement of FMPS in humans and that this estimation is correlated with an indirect estimation of WBPS.

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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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