Regulation of Protein Metabolism in Liver

Mortimore, Glenn E.; Kadowaki, Motoni

doi:10.1002/cphy.cp070217

Cited by 4 publications

(2 citation statements)

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“…The concentrations of branched amino acids they employed were 4–10 mM, which is 10–20 times higher than those used in the present study. The concentrations of amino acids we used are much closer to those found in physiological conditions [20]. Stimulation of p70 S6k activity by leucine was observed in a time‐ and dose‐dependent manner, as shown in Fig.…”

Section: Resultssupporting

confidence: 58%

“…Cells were first incubated in αMEM without FCS for 24 h, washed once with amino acid‐deprived medium and incubated in the same medium for 2 h. Then, the cells were incubated with the media containing various amino acids or amino acid derivatives as indicated in each experiment. The concentration of each amino acid except for tryptophan designated 1× is equivalent to that found in perfusate basal plasma of rat [20]as follows (in μM): arginine, 220; cystine, 34; glutamine, 716; histidine, 92; isoleucine, 114; leucine, 204; lysine, 408; methionine, 60; phenylalanine, 96; proline, 437; serine, 657; threonine, 329; tyrosine, 98; valine, 250. The concentration of tryptophan in DMEM (78 μM) is employed as 1× concentration.…”

Section: Methodsmentioning

confidence: 99%

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Structural requirement of leucine for activation of p70 S6 kinase

et al. 1999

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The addition of leucine induced activation of p70 Tk in amino acid-depleted H4IIE cells. Whereas the activation of p70 Tk by leucine was transient, the complete amino acid stimulated p70 Tk more persistently. The effect of leucine on p70 Tk was sensitive to rapamycin, but less sensitive to wortmannin. Using various amino acids and derivatives of leucine, we found that the chirality, the structure of the four branched hydrocarbons, and the primary amine are required for the ability of leucine to stimulate p70 Tk , indicating that the structural requirement of leucine to induce p70 Tk activation is very strict and precise. In addition, some leucine derivatives exhibited the ability to stimulate p70 Tk and the other derivatives acted as inhibitors against the leucine-induced activation of p70 Tk .z 1999 Federation of European Biochemical Societies.

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Section: Resultssupporting

confidence: 58%

Section: Methodsmentioning

confidence: 99%

Structural requirement of leucine for activation of p70 S6 kinase

et al. 1999

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Amino Acids as Regulators of Proteolysis

Kadowaki

Kanazawa

2003

The Journal of Nutrition

144

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Proteolysis, as well as protein synthesis, is a major process that contributes to the body protein turnover. Despite the huge variety of proteases in the body, there are very few proteolytic systems contributing to the complete hydrolysis of proteins to amino acids. The autophagic-lysosomal pathway is responsible for bulk proteolysis, whereas the ubiquitin-proteasome pathway plays a significant role in the fine control of the degradation of specific proteins. Both systems can produce free amino acids as a final product, but only the autophagy system is physiologically controlled by plasma amino acids. Recently, the study of amino acids as regulators of macromolecular turnover has been focused on for their signal transduction mechanism. In autophagic proteolysis, several amino acids have a direct regulatory potential: Leu, Gln, Tyr, Phe, Pro, Met, Trp and His in the liver, and Leu in the skeletal muscle. These amino acids are recognized at the plasma membrane, indicating the possible existence of an amino acid receptor/sensor for their recognition and subsequent intracellular signaling. Another line of evidence has emerged that protein kinase cascades such as mTOR, Erk, eIF2alpha etc. may be involved in the regulation of autophagy, and that amino acids, in combination with insulin, may exert their effects through these pathways. From the viewpoint of amino acid safety, the contribution of proteolysis to possible adverse effects caused by excessive amino acid intake is not clear. At present, there is one report that excess glutamine at 10-fold the plasma level has an abnormal inhibitory effect on hepatic proteolysis, due to a lysosomotropic toxicity of ammonia derived from glutamine degradation. Whether this may lead to an adverse effect in humans remains to be clarified.

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Whole-Body and Hindlimb Protein Breakdown Are Differentially Altered by Feeding in Neonatal Piglets

Thivierge

Bush

Suryawan

et al. 2005

The Journal of Nutrition

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The high rate of muscle protein accretion in neonates is sustained by the marked increase in muscle protein synthesis in response to feeding. Little is known about the role of proteolysis in the regulation of protein accretion in response to feeding during the neonatal period. To determine the feeding-induced response of protein breakdown at the whole-body level and in the hindlimb of neonates, 10- and 28-d-old piglets that had been food deprived overnight were infused (7 h) with [1-13C]phenylalanine and [ring-2H4]tyrosine during an initial food deprivation period (3 h), followed by a feeding period (4 h). During feeding, endogenous flux of phenylalanine decreased (P < 0.01) in both the whole body and the hindlimb. Feeding reduced (P < 0.01) whole-body proteolysis but increased hindlimb proteolysis (P = 0.04), suggesting that tissues other than the hindlimb are involved in the reduction in whole-body proteolysis during feeding. Overnight food deprivation resulted in a net mobilization of phenylalanine from whole-body proteins (P < 0.01) but not hindlimb proteins. These responses were unaffected by age. The results suggest that the hindlimb requires a continuous supply of free amino acids to sustain the high rate of muscle protein turnover in neonates and that adaptive mechanisms provide free amino acids to sustain skeletal muscle protein accretion in early postnatal life when the amino acid supply is limited.

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Regulation of Protein Metabolism in Liver

Abstract: The sections in this article are: Turnover of Cellular Protein and RNA Determination of General Protein Turnover Classes of General Protein Turnover Cytoplasmic RNA Turnover Autophagy Macroautophagy Microautophagy A Unified Mechani… Show more

Cited by 4 publications

References 132 publications

Structural requirement of leucine for activation of p70 S6 kinase

Structural requirement of leucine for activation of p70 S6 kinase

Amino Acids as Regulators of Proteolysis

Whole-Body and Hindlimb Protein Breakdown Are Differentially Altered by Feeding in Neonatal Piglets

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