Competition for transport of amino acids into rat heart: Effect of competitors on protein synthesis and degradation

Nutrients act both directly and indirectly to modulate muscle protein accretion through changes in protein synthesis and degradation. For example, glucose, amino acids and fatty acids can all be metabolized to produce energy in the form of ATP that can be utilized for protein synthesis. In addition, amino acids are used directly for the synthesis of new proteins. Nutrients also regulate protein synthesis through activation of a signalling pathway involving the protein kinase, mTOR [mammalian TOR (target of rapamycin)]. Together with several regulatory proteins, mTOR forms a complex referred to as TORC1 (TOR complex 1). Because of its central role in controlling cell growth, TORC1 is an integral component of the mechanism through which nutrients modulate protein synthesis. Herein, the mechanism(s) through which nutrients, and in particular amino acids, regulate signalling through TORC1 will be discussed. In addition, downstream effectors of TORC1 action on mRNA translation will be briefly presented. Finally, a previously unrecognized effector of TORC1 signalling in regulating protein synthesis will be described.

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Regulation of protein turnover by glucose, insulin, and amino acids in adipose tissue

AJP Cell Physiology ◽

10.1152/ajpcell.1984.247.3.c228 ◽

1984 ◽

Vol 247 (3) ◽

pp. C228-C233 ◽

Cited By ~ 15

Author(s):

M. E. Tischler ◽

A. H. Ost ◽

B. Spina ◽

P. H. Cook ◽

J. Coffman

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Adipose Tissue ◽

Aminooxyacetic Acid ◽

Protein Breakdown ◽

Inhibitory Effects ◽

Altered Protein ◽

Net Protein ◽

Protein Synthesis And Degradation ◽

Synthesis And Degradation

Protein synthesis and degradation were measured simultaneously in epididymal fat pads of rats by use of the incorporation of [14C]phenylalanine into protein and the sum of net protein breakdown and protein synthesis, respectively. Neither glucose nor insulin altered protein synthesis, but together they promoted this process; pyruvate could be substituted for glucose. Separately, glucose or insulin diminished proteolysis, and these effects were additive. In the presence of glucose and insulin, leucine, alanine, glutamine, glutamate, and aspartate lowered protein degradation to varying degrees but did not alter protein synthesis. Glutamate, but not leucine or alanine, was inhibitory without glucose and insulin present. When aminooxyacetic acid was provided to decrease the rate of transamination of amino acids, the inhibitory effects of leucine, alanine, and aspartate, but not of glutamate, appeared to be diminished. alpha-Ketoglutarate, but neither alpha-ketoisocaproate nor pyruvate, could diminish proteolysis. Inhibition of proteolysis was associated with a higher tissue content of glutamate and a greater production of glutamate and glutamine. These results suggest that glutamate itself may inhibit proteolysis in adipose tissue and mediate, at least in part, the effects of other amino acids.

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Protein turnover in pulmonary macrophages Utilization of amino acids derived from protein degradation

Biochemical Journal ◽

10.1042/bj1980053 ◽

1981 ◽

Vol 198 (1) ◽

pp. 53-65 ◽

Cited By ~ 19

Author(s):

J A Hammer ◽

D E Rannels

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Amino Acid ◽

Protein Degradation ◽

Plasma Concentrations ◽

Specific Radioactivity ◽

Pulmonary Macrophages ◽

Protein Synthesis And Degradation ◽

Synthesis And Degradation ◽

Extracellular Amino Acid

Conditions were defined under which rates of protein synthesis and degradation could be estimated in alveolar macrophages isolated from rabbits by pulmonary lavage and incubated in the presence of plasma concentrations of amino acids and 5.6 mM-glucose. Phenylalanine was validated as suitable precursor for use in these studies: it was not metabolized appreciably, except in the pathways of protein synthesis and degradation; it entered the cells rapidly; it maintained a stable intracellular concentration; and it was incorporated into protein at measurable rates. When extracellular phenylalanine was raised to a concentration sufficient to minimize dilution of the specific radioactivity of the precursor for protein synthesis with amino acid derived from protein degradation, the specific radioactivity of phenylalanyl-tRNA was only 60% of that of the extracellular amino acid. This relationship was unchanged in cells where proteolysis increased 2.5-fold after uptake and degradation of exogenous bovine serum albumin. In contrast, albumin prevented the decrease in phenylalanine incorporation observed in macrophages deprived of an exogenous source of amino acids. These observations suggested that macrophages preferentially re-utilized amino acids derived from the degradation of endogenous, but not from exogenous (albumin), protein. However, when the extracellular supply of amino acids was restricted, substrates derived from albumin catabolism could support the protein-synthetic pathway.

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