Abstract
Cells have a constant turnover of proteins that recycle most amino acids over time. Net loss is mainly due to amino acid oxidation. Homeostasis is achieved through exchange of essential amino acids with non-essential amino acids and the transfer of amino groups from oxidised amino acids to amino acid biosynthesis. This homeostatic condition is maintained through an active mTORC1 complex. Under amino acid depletion, mTORC1 is inactivated. This increases the breakdown of cellular proteins through autophagy and reduces protein biosynthesis. The general control non-derepressable 2/ATF4 pathway may be activated in addition, resulting in transcription of genes involved in amino acid transport and biosynthesis of non-essential amino acids. Metabolism is autoregulated to minimise oxidation of amino acids. Systemic amino acid levels are also tightly regulated. Food intake briefly increases plasma amino acid levels, which stimulates insulin release and mTOR-dependent protein synthesis in muscle. Excess amino acids are oxidised, resulting in increased urea production. Short-term fasting does not result in depletion of plasma amino acids due to reduced protein synthesis and the onset of autophagy. Owing to the fact that half of all amino acids are essential, reduction in protein synthesis and amino acid oxidation are the only two measures to reduce amino acid demand. Long-term malnutrition causes depletion of plasma amino acids. The CNS appears to generate a protein-specific response upon amino acid depletion, resulting in avoidance of an inadequate diet. High protein levels, in contrast, contribute together with other nutrients to a reduction in food intake.
Highlights
Cells have a constant turnover of proteins that recycle most amino acids over time
Amino acids are one of the main building blocks of life and are used in a variety of ways by mammalian cells and organisms. (i) Twenty proteinogenic L-amino acids form the building blocks for protein synthesis. (ii) Amino acids are fuels and are metabolised by most cells with a similar energy yield as carbohydrates. (iii) Amino acids are the precursors for many hormones, neurotransmitters and other specialised metabolites such as polyamines, creatine, phosphatidylserine etc. (iv) Amino acids are the principal generators of C1 carbon compounds. (v) Amino acids are important anaplerotic metabolites providing intermediates for the TCA cycle and gluconeogenesis. (vi) Non-essential amino acids can be synthesised by many cells from metabolic intermediates, but essential amino acids must be acquired from nutrients
The general control non-derepressable 2 (GCN2)/activating transcription factor 4 (ATF4) pathway may be activated in addition, resulting in transcription of genes involved in amino acid transport and biosynthesis of non-essential amino acids
Summary
Research School of Biology, Australian National University, Linnaeus Way 134, Canberra, ACT 2601, Australia. Cells have a constant turnover of proteins that recycle most amino acids over time. This increases the breakdown of cellular proteins through autophagy and reduces protein biosynthesis. Systemic amino acid levels are tightly regulated. Food intake briefly increases plasma amino acid levels, which stimulates insulin release and mTOR-dependent protein synthesis in muscle. Short-term fasting does not result in depletion of plasma amino acids due to reduced protein synthesis and the onset of autophagy. The CNS appears to generate a protein-specific response upon amino acid depletion, resulting in avoidance of an inadequate diet. Amino acids are one of the main building blocks of life and are used in a variety of ways by mammalian cells and organisms. The authors apologise for any oversight or omission of many important studies in this area
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