![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
University of Texas Medical Branch and Shriners Burns Hospital, Departments of Surgery and Metabolism Unit, Galveston, TX 77550
3To whom correspondence should be addressed. E-mail: rwolfe{at}utmb.edu.
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTS AND DISCUSSIONSUMMARYLITERATURE CITED |
|---|
KEY WORDS: • amino acids • skeletal muscle • anabolism • net balance • stable isotope
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS AND DISCUSSIONSUMMARYLITERATURE CITED |
|---|
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS AND DISCUSSIONSUMMARYLITERATURE CITED |
|---|
). This method uses stable isotope tracer methodology. When a tracer of an essential amino acid (EAA) such as phenylalanine (Phe) is used that is neither synthesized nor oxidized in muscle, uptake and appearance of the tracer can be equated to rates of MPS and breakdown. The difference between synthesis and breakdown, i.e., the net balance, is the pertinent parameter relevant to the net gain (anabolism) or loss (catabolism) of muscle. Therefore, the primary end point discussed in this paper will be net Phe balance across muscle. Net balance is the result of the balance between MPS and breakdown, which are each regulated, potentially independently. Therefore, in addition to net balance, regulation of both MPS and breakdown will be discussed. In that regard, some data will be expressed as fractional synthetic rate, which is determined by the rate of direct incorporation of tracer into the product protein (2
). |
RESULTS AND DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS AND DISCUSSIONSUMMARYLITERATURE CITED |
|---|
There is a close relationship in normal volunteers between the availability of amino acids, i.e., the rate at which amino acids enter the free intracellular pool from inward transport and from breakdown, and the rate of MPS. Furthermore, when amino acids are infused intravenously the rate of inward transport is stimulated and the rate of MPS is stimulated correspondingly (Fig. 1
) (3
). The simplest interpretation of these observations is that amino acid availability drives MPS via availability. However, this explanation is not consistent with all available data. Thus, we have shown that even when plasma amino acids double and MPS increases correspondingly, the intracellular concentrations of EAA is either not increased or even decreases slightly (Bohe, J., Low, A., Wolfe, R. R. and Rennie, M. J., unpublished results). Furthermore, basal concentrations of amino acids are apparently sufficient to maintain sufficient charging of transfer RNA (tRNA) to support a significant increase in the rate of MPS (4
). Thus, it is more likely that changes that occur in extracellular amino acid concentrations serve as signals to activate the synthetic process, and that once synthesis is activated this results in an increased rate of inward transport. Thus, regulation of the intracellular concentrations serves to maintain availability of amino acids as they are used at an accelerated rate for incorporation into protein (5
).
|
50% below the normal basal level (Kobayashi, H., Borsheim, E., Traber, D. L., Badalamenti, J., Anthony, T. G., Kimball, S. R., Jefferson, L. S. and Wolfe, R. R., unpublished results). After 2 h, amino acids were replaced in half of the animals. When concentrations were reduced there was a corresponding reduction in MPS. Inward transport was also reduced, so intracellular concentrations remained constant. Synthesis returned to the basal rate when amino acids were replaced, whereas synthesis remained suppressed for the entire 4 h of hemodialysis in which amino acids were not replaced. Thus, return of the signal to increase or decrease synthesis was similar in both circumstances; i.e., changes in extracellular concentrations signal corresponding changes in synthesis. However, at a molecular level the mechanisms are apparently different in the two circumstances.
The initiation of mRNA translation is a key regulatory process that responds to changes in amino acid concentrations. Translation initiation is a complex multi-step process requiring more than a dozen eukaryotic initiation factors (eIF) (6
,7
). At least two steps in the initiation pathway are subject to regulation in vivo: 1) binding of initiator methionyl-tRNA to the 40 S ribosomal subunit, and 2) binding of mRNA to the 43 S preinitiation complex. The activity of eIF2B is involved in the first step. Adequate amino acid availability, i.e., charging of tRNA, is necessary for a decrease in eIF2a phosphorylation and, in turn, the increase in eIF2B activity necessary to initiate the synthetic process. In the 1970s several investigators expressed the perspective that amino acids acted via the extent of charging of tRNA (8
–10
). However, it has been shown that the Km values for the tRNA charging enzymes are generally low, and thus there should be sufficient amino acids for adequate charging in muscle in the basal state (11
). Furthermore, although direct measurements of tRNA charging have been limited, it appears that in liver the tissue content of charged tRNA is relatively stable in a number of circumstances in which protein synthesis changes, so it is unlikely that tRNA charging is a direct regulator of synthesis (12
). Furthermore, we have shown that during the infusion of amino acids at rates sufficient to increase plasma concentrations in the normal physiological range, MPS is stimulated whereas the intracellular concentrations remain either unchanged or slightly depressed (Bohe, J., Low, A., Wolfe, R. R. and Rennie, M. J., unpublished results). Because the amino acids involved in charging of muscle tRNA apparently come from the intracellular pool (13
), our results are consistent with the notion that a stimulation of MPS above the normal basal rate is not mediated by an increase in tRNA charging. Thus, it appears under physiological circumstances that factors such as amino acids that stimulate MPS above the basal rate do not act via changes in eIF2B activity. In contrast, we found that when plasma amino acid concentrations were decreased by hemodialysis the guanine nucleotide exchange activity of eIF2B dropped promptly in association with the reduction in protein synthesis (Kobayashi, H., Borsheim, E., Traber, D. L., Badalamenti, J., Anthony, T. G., Kimball, S. R., Jefferson, L. S. and Wolfe, R. R., unpublished results). When the amino acids were replaced after 2 h of dialysis, the decreased eIF2B activity returned to normal and MPS increased. It thus appears that, when amino acid availability is insufficient, initiation of protein synthesis is limited by insufficient eIF2B activity and therefore other mechanisms that might normally stimulate MPS via the binding of mRNA to the 43 S preinitiation complex (e.g., insulin) would be expected to be ineffective. It could therefore appear that eIF2B activity functions in a permissive role at the physiological level. Rather, stimulation of an increase in MPS above the basal rate is apparently regulated by increased binding of mRNA to the 43 S preinitiation complex, which is caused by increased eIF4G association with eIF4E (4
).
Amino acids and muscle protein breakdown
In vitro experiments indicate a role of amino acids in regulating muscle protein breakdown (14
). However, in normal subjects infusion or ingestion of amino acids had no effect on breakdown (3
). Similarly, reduction of amino acid concentrations in normal pigs had no effect on breakdown (Kobayashi, H., Borsheim, E., Traber, D. L., Badalamenti, J., Anthony, T. G., Kimball, S. R., Jefferson, L. S. and Wolfe, R. R., unpublished results). However, the response is different when breakdown is accelerated in a catabolic state. In severely burned patients muscle protein catabolism results from an accelerated rate of breakdown that exceeds the extent of increase in synthesis (15
). In these patients infusion of amino acids suppressed breakdown, whereas synthesis was not affected. Thus, an elevation in amino acid concentrations in vivo only suppresses accelerated muscle protein breakdown.
Composition of amino acid mixture and MPS
Amino acids that can be synthesized in the body at rates adequate to meet basal requirements are considered to be nonessential amino acids (NEAA). However, it is not clear whether ingestion of one or more of these amino acids is necessary to support accelerated MPS resulting from supplement ingestion. We had previously shown that MPS was stimulated to a similar extent when 40 g of either a balanced mixture of EAA and NEAA or the same amount of EAA only was ingested in small doses over 3 h (16
). These results indicated that ingestion of NEAA was not normally needed for MPS to be stimulated when EAA were ingested. In contrast, because substitution of 50% of the EAA with NEAA did not reduce the magnitude of stimulation it could be that the NEAA can be used as effectively as the EAA. Alternatively, because we have shown that there is a limit to the extent to which MPS can be stimulated during constant intake (Bohe, J., Low, A., Wolfe, R. R. and Rennie, M. J., unpublished results), it is possible that the 20 g of EAA given in the balanced mixture already exceeded the maximal dose. In this case, amino acids given in excess of 20 g whether or not the amino acids were "essential" would not be used for synthesis. To more directly test whether the ingestion of NEAA is necessary for the stimulation of MPS, individuals were given 30 g of a balanced mixture of amino acids (EAA + NEAA) continuously over 3 h. The study was then repeated, but only the EAA in the mixture were given (14 g). The results are summarized in Figure 2
. The responses of MPS and net muscle balance (shown in Fig. 2
) were almost identical, although only half the total amino acids were given in the EAA group as in the group given EAA + NEAA. These results showed that NEAA are not needed for the stimulation of MPS by exogenous EAA.
|
The response of MPS to a bolus of amino acids is quite different from the response to a constant infusion. There is a rapid increase in MPS in conjunction with the rise in EAA concentration, and an equally rapid fall as the EAA concentrations begin to decrease (Fig. 3
). However, the rate of MPS returned to the basal value well before the concentration fell to the basal level. In fact, in the example shown in Figure 3
, after ingestion of 15 g of EAA, net balance (as well as the rate of MPS) had returned to the basal rate when the plasma concentration was still more than double the basal value. In contrast, when plasma concentrations were increased to a steady-state concentration for 3 h at a value twice above the basal value, the maximal stimulation of MPS was achieved (17
). Furthermore, whereas the response to a bolus is transient, the peak response may be 6- to 10-fold the basal value. Nonetheless, because of the transient nature of the response, the total synthetic response (area under curve of synthesis vs. time) was less than when similar doses of amino acids were taken in the constant intake mode as opposed to the bolus ingestion (Fig. 4
). Thus, different mechanisms appear to be operative in response to the mode of ingestion. Clarification of these mechanisms could lead to amplifying the response to a given amount of intake.
|
|
To test the independent and potentially interactive effects of amino acids and carbohydrate intake normal volunteers were given drinks containing 30 g of a balanced amino acid mixture alone, 30 g of glucose alone or a combination of 30 g each of amino acids and glucose. The drinks were consumed in small amounts over 3 h, resulting in essentially steady state elevations in concentrations of amino acids, glucose and insulin in the plasma. The stimulation of net MPS by amino acids alone is shown in Figure 2
. Glucose alone had no significant effect on MPS. However, when the glucose was added to the amino acids there was an interactive effect, meaning that the stimulation of net MPS was more than the sum of the individual responses (17
). This interactive effect is understandable when considered in light of the response of MPS to insulin and the discussion above of the permissive nature of eIF2B activity.
Whereas insulin has long been recognized as an important anabolic hormone, its specific role in regulation of MPS in human subjects has been the subject of debate. Whereas in vitro experiments have clearly demonstrated a stimulatory effect of insulin on MPS, studies in human subjects have yielded inconsistent results (see Ref. 18
for review). However, when the role of amino acid concentrations in the regulation of MPS is considered, the apparently contradictory in vivo results can be largely reconciled. When glucose/insulin are given alone, such as during the euglycemic/hyperinsulinemic clamp procedure, plasma amino acid levels fall. The effect of a reduction in amino acid levels was discussed above. Thus, although insulin itself has a stimulatory effect on synthesis, an adequate eIF2B activity is required for that potential effect to translate into an increased rate of synthesis, and this is not the case when amino acid levels fall. Consequently, studies in which plasma amino acid levels were allowed to drop during insulin infusion have generally failed to show a stimulatory effect of insulin on MPS. In contrast, when the effect of insulin has been assessed in the context of maintained (e.g., Ref. 19
) or elevated (e.g., Ref. 20
), concentrations of amino acids have been found to stimulate synthesis. Thus, the interactive response of MPS to carbohydrate plus amino acids described above can be predicted, although carbohydrate intake alone has minimal effect.
Resistance exercise and amino acid intake
The response of muscle protein metabolism varies in magnitude according to the exact nature of intensity of exercise and the method used to quantify the response. Studies determining the fractional synthetic rate have consistently shown a stimulation after exercise (e.g., Ref. 21
), and although results from the A-V balance method have been less consistent, a stimulation of synthesis has been observed with this method as well when the exercise involved several muscle groups of the leg (22
). However, breakdown is also elevated, so that the balance between synthesis and breakdown does not become positive (22
). Thus, nutritional intake is required for resistance exercise to be anabolic.
The response to amino acid intake after exercise is dependent on the composition and amount, as well as the pattern and timing of ingestion in relation to the performance of exercise. We assessed the effect of composition and amount of amino acids by comparing the response to two doses, given 1 h apart, of 6 g each of a mixture of EAA only versus 6 g of a balanced mixture (EAA + NEAA) (Borsheim, E., Tipton, K. D., Wolf, S. E. and Wolfe, R. R., unpublished results). The balanced mixture contained 3 g of EAA per dose. The total response to the two doses of 6 g of EAA was double the response to the balanced mixture. In addition, in each case the response to the second dose was the same as to the first. This was true even though when the second dose was given the response of net MPS to the fist dose had returned to the basal rate, despite the persistent elevation in concentration after the first dose. Thus, it appears that an increasing concentration activates the synthetic process and the decline in concentration decreases synthesis, irrespective of the absolute value of the concentration. We also assessed the effect of the addition of 35 g of glucose to either the balanced or EAA mixtures (Borsheim, E., Tipton, K. D., Wolf, S. E. and Wolfe, R. R., unpublished results; Miller, S. L., Tipton, K. D., Chinkes, D. L., Wolf, S. E. and Wolfe, R. R., unpublished results). In contrast to the situation at rest, no interactive or even additive glucose effect was observed. This absence of anabolic effect of carbohydrate is consistent with the absence of action of local hyperinsulinemia on muscle protein metabolism after exercise (23
). In contrast, local hyperinsulinemia stimulates MPS in resting individuals (20
).
Timing of intake in relation to exercise
In the experiments described above the amino acids ± glucose were given after exercise. No difference in response was observed when EAA + glucose were given at 1 versus 3 h after exercise (24
). Similarly, when the same mixture was given immediately after exercise the response of MPS was the same as when given 1 h after exercise (25
). However, when the EAA/glucose mixture was given immediately before exercise the response was greatly amplified. Not only was the increase during exercise approximately fourfold above the basal value, the response in the first hour after exercise was just as large as the response over the same time interval when the supplement was given immediately after exercise (Fig. 5
). When total area under the curve was calculated, the response was approximately threefold greater when the drink was given after exercise than at rest, and approximately double the response as when ingested after exercise (25
).
|
In a general sense protein synthesis is stimulated after food is ingested and it is decreased when the individual is in the postabsorptive state. Conventionally this corresponds to a diurnal cycle, with synthesis being elevated in waking hours and depressed during sleep. It has been proposed that, once maintenance requirements are achieved, additional protein intake has no effect on 24-h whole-body protein balance, because the elevated peak during the day is balanced by a greater nadir in the evening (26
). However, this proposed response is at odds with considerable experimental data indicating that, as protein intake increases, total amino acid retention increases, even when intake is above that required for amino acid balance (27
). We therefore tested whether acute acceleration of MPS, as we have demonstrated above in response to exercise plus amino acids, translates to a comparable increase in net balance over 24 h, or rather if an acute increase is counterbalanced by a corresponding nadir in the night. On 1 day normal volunteers were given two doses of amino acids plus glucose, one before and one after a bout of resistance exercise, to provide a potent acute stimulation of MPS. On a second occasion they rested during the corresponding time. The subjects were given the same meals and treated identically over 24 h, other than the exercise/amino acid supplementation. A-V samples were taken throughout the entire 24 h. The results showed that the stimulated net balance over 3 h in the exercise/amino acid supplementation group translated to almost the identical gain over 24 h. Net balance throughout the night was almost identical in the two groups. Fractional synthetic rate values over the 24 h confirmed the conclusions from the 24-h net balance data. Thus, acute stimulation of muscle protein metabolism does not affect rates of synthesis at later times when there is no food intake.
Relation of findings to protein requirements
The results presented here establish a direct role of amino acids in regulating net muscle protein balance. Furthermore, the response is directly affected by the exact composition and amount of mixture of amino acids ingested, the timing of ingestion in relation to exercise and the amount and nature of nonprotein energy ingested with amino acids. When these findings are considered in the context of the estimation of protein or amino acid "requirements," it is clear that multiple results could be achieved for the same AMINO ACID intake, depending on the interaction of the various factors discussed above. Thus, attempts to identify a unique AMINO ACID "requirement" are likely to be unsuccessful. Furthermore, our results, along with virtually all data in the literature on the topic, suggest that increasing AMINO ACID intake will increase muscle mass, with all other variables remaining constant. Whereas this concept runs counter to popular perception, real-life examples abound in obese individuals who have significantly elevated muscle mass despite living sedentary lives (e.g., Ref. 28
). Thus, it is likely that increasing AMINO ACID intake in accord with the principles discussed above to optimize effectiveness will promote muscle anabolism, whether in depleted individuals such as the elderly or in active athletes trying to increase muscle mass. The exact nutritional approach will determine the extent of anabolic response.
|
SUMMARY |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS AND DISCUSSIONSUMMARYLITERATURE CITED |
|---|
|
FOOTNOTES |
|---|
2 Supported by Shriners Hospitals for Children Grant 8490 and National Institutes of Health grant AG15780.
4 Abbreviations used: A-V, arteriovenous; EAA, essential amino acid; eIF, eukaryotic initiation factor; Met-tRNA, MPS, muscle protein synthesis; NEAA, nonessential amino acid; Phe, phenylalanine; tRNA, transfer RNA.
|
LITERATURE CITED |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS AND DISCUSSIONSUMMARYLITERATURE CITED |
|---|
1. Biolo, G., Fleming, R. Y., Maggi, S. P. & Wolfe, R. R. (1995) Transmembrane transport and intracellular kinetics of amino acids in human skeletal muscle. Am. J. Physiol. 268:E75-E84.
2. Carraro, F., Stuart, C. A., Hartl, W. H., Rosenblatt, J. & Wolfe, R. R. (1990) Effect of exercise and recovery on muscle protein synthesis in human subjects. Am. J. Physiol. 259:E470-E476.
3. Biolo, G., Tipton, K. D., Klein, S. & Wolfe, R. R. (1997) An abundant supply of amino acids enhances the metabolic effect of exercise on muscle protein. Am. J. Physiol. 36:E122-E129.
4. Anthony, J. C., Anthony, T. G., Kimball, S. R., Vary, T. C. & Jefferson, L. S. (2000) Orally administered leucine stimulates protein synthesis in skeletal muscle of postabsorptive rats in association with increased eIF4F formation. J. Nutr. 130:139-145.
5. Wolfe, R. R. & Miller, S. L. (1999) Amino acid availability controls muscle protein metabolism. Diabetes Nutr. Metab. 12:322-328.[Medline]
6. Pain, V. M. (1996) Initiation of protein synthesis in eukaryotic cells. Eur. J. Biochem. 236:747-771.[Medline]
7. Voorma, H. O., Thomas, A. A. & Van Heugten, H. A. (1994) Initiation of protein synthesis in eukaryotes. Mol. Biol. Rep. 19:139-145.[Medline]
8. Adibi, S. A., Modesto, T. A., Morse, E. L. & Amin, P. M. (1973) Amino acid levels in plasma, liver, and skeletal muscle during protein deprivation. Am. J. Physiol. 225:408-414.
9. Lunn, P. G., Whitehead, R. G. & Baker, B. A. (1976) The relative effects of a low-protein-high-carbohydrate diet on the free amino acid composition of liver and muscle. Br. J. Nutr. 36:219-230.[Medline]
10. Heard, C. R., Frangi, S. M. & Wright, P. M. (1977) Biochemical characteristics of different forms of protein-energy malnutrition: an experimental model using young rats. Br. J. Nutr. 37:1-21.[Medline]
11. Rogers, Q. R. (1976) Cole, D. J. Boorman, K. N. Bittery, P. J. Lewis, D. Neale, R. J. Swan, H eds. Protein Metabolism and Nutrition 1976:279-301 Butterworth London, UK. .
12. Jamaa, K., Kimball, S. R. & Jefferson, L. S. (1993) Aminoacylation of initiator methionyl-tRNAi under conditions of inhibitory initiation of protein synthesis. Am. J. Physiol. 264:E257-E263.
13. Bauman, P. Q., Stirewalt, W. S., O’Rourke, B. D., Howard, D. & Nair, K. S. (1994) Precursor pools of protein synthesis: a stable isotope study in swine model. Am. J. Physiol. 267:E203-E209.
14. Mortimore, G. E., Wert, J. J., Miotto, G., Venerando, R. & Kadowaki, M. (1994) Leucine-specific binding of photoreactive Leu-7-MAP to a high molecular weight protein on the plasma membrane of the isolated rat hepatocyte. Biochem. Biophys. Res. Commun. 203:200-208.[Medline]
15. Biolo, G., Fleming, R. Y., Maggi, S. P., Nguyen, T. T., Herndon, D. N. & Wolfe, R. R. (2002) Inverse regulation of protein turnover and amino acid transport in skeletal muscle of hypercatabolic patients. J. Clin. Endocrinol. Metab. 87:3378-3384.
16. Tipton, K. D., Gurkin, B. E., Matin, S. & Wolfe, R. R. (1999) Nonessential amino acids are not necessary to stimulate net muscle protein synthesis in healthy volunteers. J. Nutr. Biochem. 10:89-95.[Medline]
17. Volpi, E., Mittendorfer, B., Rasmussen, B. B. & Wolfe, R. R. (2000) The response of muscle protein anabolism to combined hyperaminoacidemia and glucose-induced hyperinsulinemia is impaired in the elderly. J. Clin. Endocrinol. Metab. 85:4481-4490.
18. Wolfe, R. R. & Volpi, E. (2001) Insulin and protein metabolism. Jefferson, L. S. Cherrington, A. D. eds. Handbook of Physiology. Section 7 II:735-757 Oxford New York, NY. .
19. Biolo, G., Fleming, R. Y. & Wolfe, R. R. (1995) Physiologic hyperinsulinemia stimulates protein synthesis and enhances transport of selected amino acids in human skeletal muscle. J. Clin. Invest. 95:811-819.
20. Hillier, T. A., Fryburg, D. A., Jahn, L. A. & Barrett, E. J. (1998) Extreme hyperinsulinemia unmasks insulin effect to stimulate protein synthesis in the human forearm. Am. J. Physiol. 274:E1067-E1074.
21. Phillips, S. M., Tipton, K. D., Ferrando, A. A. & Wolfe, R. R. (1999) Resistance training reduces the acute exercise-induced increase in muscle protein turnover. Am. J. Physiol. 276:E118-E124.
22. Biolo, G., Maggi, S. P., Williams, B. D., Tipton, K. & Wolfe, R. R. (1995) Increased rates of muscle protein turnover and amino acid transport after resistance exercise in humans. Am. J. Physiol. 268:E514-E520.
23. Biolo, G., Williams, B. D., Fleming, R. Y. & Wolfe, R. R. (1999) Insulin action on muscle protein kinetics and amino acid transport during recovery after resistance exercise. Diabetes 48:949-957.[Abstract]
24. Rasmussen, B., Tipton, K. D., Miller, S. L., Wolf, S. E. & Wolfe, R. R. (2000) An oral essential amino acid-carbohydrate supplement enhances muscle protein anabolism after resistance exercise. J. Appl. Physiol. 88:386-392.
25. Tipton, K. D., Rasmussen, B. B., Miller, S. L., Wolf, S. E., Owens-Stovall, S. K., Petrini, B. E. & Wolfe, R. R. (2001) Timing of amino acid-carbohydrate ingestion alters anabolic response of muscle to resistance exercise. Am. J. Physiol. 281:E197-E206.
26. Pacy, P. J., Price, G. M., Halliday, D., Quevedo, M. R. & Millward, D. J. (1994) Nitrogen homeostasis in man: the diurnal responses of protein synthesis and degradation and amino acid oxidation to diets with increasing protein intakes. Clin. Sci. (Lond.) 86:103-116.[Medline]
27. Hegsted, D. M. (1978) Assessment of nitrogen requirements. Am. J. Clin. Nutr. 31:1669-1677.
28. Hibbert, J. M., Broemeling, L., Isenberg, J. N. & Wolfe, R. R. (1994) Determinants of total free-living energy expenditure in lean and obese women measured by the doubly-labeled water method. J. Obesity 2:44-53.
This article has been cited by other articles:
|
|
 |
|
  R. J. Manders, R. Koopman, M. Beelen, A. P. Gijsen, W. K. Wodzig, W. H. Saris, and L. J. van Loon The Muscle Protein Synthetic Response to Carbohydrate and Protein Ingestion Is Not Impaired in Men with Longstanding Type 2 Diabetes J. Nutr., June 1, 2008; 138(6): 1079 - 1085. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Paddon-Jones, K. R Short, W. W Campbell, E. Volpi, and R. R Wolfe Role of dietary protein in the sarcopenia of aging Am. J. Clinical Nutrition, May 1, 2008; 87(5): 1562S - 1566S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-j. Zhang, O. Irtun, D. L. Chinkes, and R. R. Wolfe Acute responses of muscle protein metabolism to reduced blood flow reflect metabolic priorities for homeostasis Am J Physiol Endocrinol Metab, March 1, 2008; 294(3): E551 - E557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Trappe, A. Creer, K. Minchev, D. Slivka, E. Louis, N. Luden, and T. Trappe Human soleus single muscle fiber function with exercise or nutrition countermeasures during 60 days of bed rest Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R939 - R947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. R. Wolfe, J. Song, J. Sun, and X.-j. Zhang Total Aminoacyl-Transfer RNA Pool Is Greater in Liver Than Muscle in Rabbits J. Nutr., November 1, 2007; 137(11): 2333 - 2338. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Trappe, A. Creer, D. Slivka, K. Minchev, and T. Trappe Single muscle fiber function with concurrent exercise or nutrition countermeasures during 60 days of bed rest in women J Appl Physiol, October 1, 2007; 103(4): 1242 - 1250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Koopman, B. Pennings, A. H. G. Zorenc, and L. J. C. van Loon Protein Ingestion Further Augments S6K1 Phosphorylation in Skeletal Muscle Following Resistance Type Exercise in Males J. Nutr., August 1, 2007; 137(8): 1880 - 1886. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. W. Booth and S. J. Lees Fundamental questions about genes, inactivity, and chronic diseases Physiol Genomics, January 17, 2007; 28(2): 146 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Gore, R. R. Wolfe, and D. L. Chinkes Quantification of amino acid transport through interstitial fluid: assessment of four-compartment modeling for muscle protein kinetics Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E319 - E323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Donatelli, T. Schricker, P. Parrella, F. Asenjo, L. Wykes, and F. Carli Intraoperative Infusion of Amino Acids Induces Anabolism Independent of the Type of Anesthesia Anesth. Analg., December 1, 2006; 103(6): 1549 - 1556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Koopman, L. Verdijk, R. J. Manders, A. P Gijsen, M. Gorselink, E. Pijpers, A. J. Wagenmakers, and L. J. van Loon Co-ingestion of protein and leucine stimulates muscle protein synthesis rates to the same extent in young and elderly lean men. Am. J. Clinical Nutrition, September 1, 2006; 84(3): 623 - 632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Katsanos, H. Kobayashi, M. Sheffield-Moore, A. Aarsland, and R. R. Wolfe A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E381 - E387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. R. Wolfe Skeletal Muscle Protein Metabolism and Resistance Exercise J. Nutr., February 1, 2006; 136(2): 525S - 528S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S Katsanos, H. Kobayashi, M. Sheffield-Moore, A. Aarsland, and R. R Wolfe Aging is associated with diminished accretion of muscle proteins after the ingestion of a small bolus of essential amino acids Am. J. Clinical Nutrition, November 1, 2005; 82(5): 1065 - 1073. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Etzel Manufacture and Use of Dairy Protein Fractions J. Nutr., April 1, 2004; 134(4): 996S - 1002S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Paddon-Jones, M. Sheffield-Moore, X.-J. Zhang, E. Volpi, S. E. Wolf, A. Aarsland, A. A. Ferrando, and R. R. Wolfe Amino acid ingestion improves muscle protein synthesis in the young and elderly Am J Physiol Endocrinol Metab, March 1, 2004; 286(3): E321 - E328. [Abstract] [Full Text]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
