Failure of leucine to stimulate protein synthesis in vivo

McNurlan, Margaret A.; Fern, E. B.; Garlick, Peter J.

doi:10.1042/bj2040831

Cited by 140 publications

(50 citation statements)

References 26 publications

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“…These data suggest that the lower rates obtained in the study presented here result from the lack of dietary protein, and lack of enteral feeding may have contributed. This is consistent with the reduction in rates of tissue protein synthesis that occurs when young rats are starved or are given a proteinfree diet (26).…”

Section: Discussionsupporting

confidence: 70%

Protein Turnover Rates in Sick, Premature Neonates during the First Few Days of Life

1991

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ABSTRACT. Rates of protein turnover were measured in 19 infants during the first few days of life while they were receiving i.v. glucose. The technique consisted of a continuous i.v. infusion of L-(1-'"]leucine to measure whole body leucine flux and determination of total urinary nitrogen excretion to assess leucine oxidation rates. Subsequent to each of the studies, the decision to start total parenteral nutrition (TPN) was made by the clinician concerned, with the result that seven infants did not start TPN and 12 did. There were significantly greater urinary nitrogen excretion ( p < 0.001) and lower rates of whole body protein synthesis ( p = 0.024) and breakdown ( p = 0.015) in those who did start TPN compared with those who did not. The marked difference in nitrogen excretion between the two groups suggests that this could be a useful determinant for deciding which neonate should start TPN. (Pediatr Res 30: 418-422,1991) Abbreviations TPN, total parenteral nutrition LBWN, low birth weight neonate N, nitrogen TBUN, total body urea nitrogen urine and, therefore, is noninvasive. With this method, the calculation of whole body protein turnover involves quantifying N kinetics per se. The alternative is to use a selected "representative" amino acid labeled with a stable isotope and, by measuring dilution of this tracer, to derive values for the metabolic turnover of that particular amino acid (7). L-[1-I3C]leucine is one such tracer that has been used to measure protein turnover in premature infants (8). This method is more invasive, in that blood samples are generally used, but in the study presented here this was possible because the infants had indwelling arterial catheters. However, a further restriction is the need for breath C 0 2 collection to assess leucine oxidation. We have therefore modified the constant infusion of [l-13C]leucine method for measuring whole body protein turnover rates by using N excretion to assess leucine oxidation. The results show differences between those infants who subsequently did or did not start TPN. MATERIALS AND METHODSPatients. Nineteen infants, gestational ages 30.4 + 1.2 wk (mean k SD) and weight 1.48 + 0.30 kg, were studied between 17 and 9 1 h postnatal age (46 & 17 h). Infants were studied only if they had an i.v. cannula in situ; all were given i.v. glucose and had similar energy intakes. None were enterally fed at the time of study. Only male infants were studied because of the need for accurate urine collection. Exclusion criteria were the presence of any metabolic disorders. renal failure. and insulin administraThe decision to start TPN in the sick LBWN is usually made on clinical grounds as well as objective parameters such as metabolic or nutritional status. Although it is undeniable that this group of infants requires adequate and appropriate nutrition for optimal development (I), the immaturity of their metabolic pathways (2) may limit tolerance to the solutions used in TPN. Some of these problems, such as acidosis (3) and hyperammonemia (4), have diminished...

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Section: Discussionsupporting

confidence: 70%

Protein Turnover Rates in Sick, Premature Neonates during the First Few Days of Life

1991

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“…The effects of fasting on hepatic protein synthesis in the suckling rats in our study were qualitatively similar to those reported in adult and young weaned rats (8)(9)(10). We found quantitative differences, however, depending on the stage of development.…”

Section: Methodssupporting

confidence: 75%

“…A short-term fast (24 h) in young growing and adult rats reduces the hepatic protein synthesis rate and protein mass by approximately 30 and 20%, respectively (8)(9)(10). Alternatively, in skeletal muscle, reduced protein synthesis in response to a short-term fast is greater in young rats than in older weaned rats (1 1, 12).…”

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confidence: 99%

Hepatic Protein Synthesis in Suckling Rats: Effects of Stage of Development and Fasting

et al. 1992

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ABSTRACT. We studied the developmental changes in hepatic protein synthesis in suckling rats between postpartum d 1 and 28 and investigated the effect of fasting for 10 or 18 h on hepatic protein turnover at postpartum d 5, 10, 16, and 28. . At all stages of development, the & and translational efficiency in fasted rats were significantly lower than those in control (fed) rats, although the relative decline in both measurements was largest at postpartum d 10. The absolute rates of hepatic protein synthesis declined to similar levels on d 5, 10, and 16 after 10 h of fasting and changed little after 18 h of fasting; this level was significantly higher at postpartum d 28. Our results suggest that postnatal development in suckling rats was marked by a biphasic pattern in the rates of hepatic protein synthesis, which increased during the neonatal and weaning periods. The relative changes in the synthesis and loss of hepatic protein in response to fasting were greater during the neonatal than during the late suckling and weaning periods.

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“…This idea originally arose from experiments on muscle in vitro, but has not been con®rmed in vivo (McNurlan et al 1982;Papet et al 1992). However, leucine does behave in a peculiar way, because in many studies plasma concentration falls in response to feeding protein, which does not seem to happen to the same extent with other amino acids.…”

Section: Fasting and Feedingmentioning

confidence: 99%

The mysteries of nitrogen balance

Waterlow¹

1999

Nutr. Res. Rev.

113

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The ®rst part of this review is concerned with the balance between N input and output as urinary urea. I start with some observations on classical biochemical studies of the operation of the urea cycle. According to Krebs, the cycle is instantaneous and automatic, as a result of the irreversibility of the ®rst enzyme, carbamoyl-phosphate synthetase 1 (EC 6.3.5.5; CPS-I), and it should be able to handle many times the normal input to the cycle. It is now generally agreed that acetyl glutamate is a necessary co-factor for CPS-1, but not a regulator. There is abundant evidence that changes in dietary protein supply induce coordinated changes in the amounts of all ®ve urea-cycle enzymes. How this coordination is achieved, and why it should be necessary in view of the properties of the cycle mentioned above, is unknown. At the physiological level it is not clear how a change in protein intake is translated into a change of urea cycle activity. It is very unlikely that the signal is an alteration in the plasma concentration either of total amino-N or of any single amino acid. The immediate substrates of the urea cycle are NH 3 and aspartate, but there have been no measurements of their concentration in the liver in relation to urea production. Measurements of urea kinetics have shown that in many cases urea production exceeds N intake, and it is only through transfer of some of the urea produced to the colon, where it is hydrolysed to NH 3 , that it is possible to achieve N balance. It is beginning to look as if this process is regulated, possibly through the operation of recently discovered urea transporters in the kidney and colon. The second part of the review deals with the synthesis and breakdown of protein. The evidence on whole-body protein turnover under a variety of conditions strongly suggests that the components of turnover, including amino acid oxidation, are in¯uenced and perhaps regulated by amino acid supply or amino acid concentration, with insulin playing an important but secondary role. Molecular biology has provided a great deal of information about the complex processes of protein synthesis and breakdown, but so far has nothing to say about how they are coordinated so that in the steady state they are equal. A simple hypothesis is proposed to ®ll this gap, based on the self-evident fact that for two processes to be coordinated they must have some factor in common. This common factor is the amino acid pool, which provides the substrates for synthesis and represents the products of breakdown. The review concludes that although the achievement and maintenance of N balance is a fact of life that we tend to take for granted, there are many features of it that are not understood, principally the control of urea production and excretion to match the intake, and the coordination of protein synthesis and breakdown to maintain a relatively constant lean body mass.

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Failure of leucine to stimulate protein synthesis in vivo

Cited by 140 publications

References 26 publications

Protein Turnover Rates in Sick, Premature Neonates during the First Few Days of Life

Protein Turnover Rates in Sick, Premature Neonates during the First Few Days of Life

Hepatic Protein Synthesis in Suckling Rats: Effects of Stage of Development and Fasting

The mysteries of nitrogen balance

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