File Name: metabolism of proteins and amino acids .zip
Not a MyNAP member yet? Register for a free account to start saving and receiving special member only perks. How protein got its name is an interesting story Hartley,
Proteins are macro-molecules crucial for cell life, which are made up of amino acids AAs. In healthy people, protein synthesis and degradation are well balanced. However, in the presence of hypercatabolic stimulation i. The biochemical consequence of hyper-catabolism is protein disarrangement, clinically evident with signs such as sarcopenia, hypalbuminemia, anaemia, infection, and altered fluid compartmentation, etc.
Hypercatabolic protein disarrangement HPD is often underestimated by clinicians, despite correlating with increased mortality, hospitalization, and morbidity quite independent of the primary disease. Simple, cheap, repeatable measurements can be used to identify HPD.
Here, we describe the metabolism of protein and AAs in hypercatabolic syndrome, illustrating the clinical impact of protein disarrangement.
We also illustrate simple, cheap, repeatable, and worldwide available measurements to identify these conditions. Finally, we provide scientific evidence for HPD nutritional treatment. Proteins are macronutrients crucial for various cellular activities, as well as body metabolism. Protein synthesis is primarily controlled by amino acid AA availability in stoichiometric quantities proportional to the number of proteins needed for synthesis and energy requirements needed to sustain the synthetic process.
AAs serve many functions within the body. This carbon skeleton can be used by the liver to produce glucose through gluconeogenesis and other macromolecules, such as lipids. NEAAs are synthetized within the body from carbohydrates and lipids deriving nitrogen from other AAs. EAAs, however, cannot be synthesized and need to be adequately introduced with the diet, and they are also the most relevant nutritional input for protein synthesis [ 3 ].
For instance, leucine is considered the primary nutritional regulator of muscle protein anabolism [ 4 ] due to its ability to trigger the mammalian target of the rapamycin mTOR pathway and inhibit the proteasome system [ 4 ]. Interestingly, under conditions such as injury, surgery, or chronic diseases, there is increased demand for AAs as a consequence of higher resting energy expenditure [ 5 ].
Such a metabolic shift is one of the main alterations leading to an imbalance between nitrogen request and nitrogen intake observed in patients with chronic altered metabolic conditions and measured as the nitrogen balance. This ultimately triggers muscle and circulating protein disarrangement that become clinically evident in several muscle-wasting conditions e.
The pathophysiology of syndromes characterized by protein disarrangement is multi-factorial and dishomogeneous. Indeed, both the elderly and patients with chronic diseases such as infections and sepsis show a pattern of circulating mediators with altered ratios between catabolic molecules e. Muscle contractile proteins and circulating visceral proteins are the major reservoir of AAs within the body.
In this context, the role of skeletal muscle and circulating visceral proteins goes well beyond that of ensuring posture maintenance and locomotion and transporting molecules or atoms. The increase in catabolic stimuli enhances protein breakdown and AA release in the blood stream. These AAs are used almost exclusively for energy production and gluconeogenesis, but not for de novo protein synthesis.
This favors the onset and aggravation of muscle wasting. The proteins of skeletal muscle and the circulatory system are in continuous turnover. Several studies indicate that about — g of proteins per day are metabolized in healthy individuals. However, this amount increases dramatically under conditions with higher metabolic demand. For instance, aged muscles have reduced anabolic response to low doses e. Therefore, it is recommended that older people consume food rich in high-quality proteins with higher proportions of EAAs, such as lean meat and other leucine-rich foods e.
Recently, protein intake above the current recommended dietary allowance RDA; 0. It, therefore, appears appropriate to promote protein intake of 1. Finally, older people with severe illnesses or overt malnutrition may need as much as 2. This reinforces the protein-amino acid disarrangement [ 10 , 19 ].
Notably, these conditions are related to increased morbidity, hospitalization, and mortality, independent of primary diseases, and so increases health-related costs and worse prognosis [ 11 , 22 ]. The central role of muscle proteins for the maintenance of whole-body metabolism, especially in response to stress e. Indeed, the maintenance of muscle mass and protein metabolism has been suggested as being a relevant parameter to include in future studies because of its clinical relevance [ 23 ].
Two major points should be considered: 1 nitrogen needs may significantly increase independent of caloric demand. This is often overlooked in large populations i. This is because dietary proteins are enriched in NEAAs, which are not fundamental to support global metabolism but do increase urea synthesis, and EAAs, which are crucial for refuelling proteins and global metabolism. Thus, insufficient intake of EAAs despite increased need may be a mechanism in obese patients with chronic disease i.
Dietary intake providing adequate protein amount and, consequently, AAs to match organ demand, preserves the integrity of organs essential for life, as witnessed by peripheral muscle homeostasis and, ultimately, patient survival.
Conversely, insufficient EAA intake induces muscle and circulating visceral protein degradation to release AAs to cope for this deficit. HS also reduces the appetite, as well as nausea and digestive disorders in patients with chronic conditions leading to inadequate nutrition and consequent reduced availability of nutrients, including AAs [ 25 ].
Anamnesis would suggest that eating-related disorders can be found in chronic patients and specific therapeutic strategies can be implemented. Altered protein metabolism in patients with chronic diseases, especially older ones, may increase the risk of developing life-threatening complications e.
Furthermore, cardiac dysfunction, ventricular arrhythmias, and renal insufficiency may also occur [ 25 ]. We have recently proposed a panel of practical and inexpensive tools for the clinical evaluation of protein disarrangement [ 26 ].
A set of indirect measurements evaluating body composition anthropometric parameters , visceral protein composition serum albumin, pre-albumin, transferrin, retinol binding protein, nitrogen balance , muscle protein degradation serum or urinary excretion of 3-metil histidine , and immuno-competence total lymphocyte count has been proposed.
However, a rapid, inexpensive, and easy assessment of protein disarrangements at the bedside is still lacking. As such, the evaluation of anthropometric parameters should be considered [ 26 ]. A simple way to evaluate body composition is to measure tricipital skin-fold thickness TST, an index of fat mass and arm muscle area AMA, an index of lean mass as described elsewhere [ 27 , 28 ]. Notably, TST and AMA are not modified by extracellular fluids, so they are useful tools even in patients with fluid retention.
Whenever protein disarrangement associated with muscle wasting and hypoalbuminemia is suspected, the following additional evaluations can be considered. The concentration of serum proteins such as albumin, pre-albumin, transferrin, and retinol binding proteins are influenced by extra-cellular fluid composition.
Albumin concentration can be included in routine clinical blood measurements as it is easy to measure, non-invasive, and a repeatable marker. Its concentration correlates with worsening morbidity and mortality independent of the disease index [ 30 ].
Concentrations lower than 3. Notably, severe nephrosis, protein-losing enteropathy, or severe liver insufficiency reduce serum albumin concentrations. Consequently, these conditions should be excluded when albumin is used as an index of protein status.
Pre-albumin responds quickly to short-term 24—36 h energy restriction and re-feeding. Repeated measurements of pre-albumin levels over a week could be a useful measure of both protein depletion and repletion. This is particularly useful to monitor treatment [ 30 ]. Transferrin correlates with mortality and is also influenced by iron metabolism. It has a half-life of about eight days and can, therefore, be used to monitor the effects of specific intervention. Retinol-binding protein has a turnover of 12 h.
Consequently, it is a measure of rapid protein metabolism modification. Nitrogen balance NB is an indirect measure of dynamic processes of endogenous protein synthesis anabolism and demolition catabolism. Two grams correspond to the nitrogen lost in feces and sweat. Notably, NB depends on urea excretion that is influenced by the daily amount of NEAAs that are routed to urea excretion.
To obtain reliable information, this parameter should be monitored frequently. M ethylation of histidine is a marker of protein degradation derived from contractile actin and myosin. A simple and rapid method to estimate the fractional catabolic rate of myofibrillar protein is the evaluation of 3-methylhistidine: creatinine excretion in the urine.
The presence of 3-MeH shows the presence of proteolysis over the immediate period-hours [ 8 , 31 , 32 ]. The loss of circulating cell-mediated immune competence is present in patients with advanced heart failure with sarcopenia and metabolism disarrangements. Indeed, the lymphocyte count could be considered an indirect index of cell proliferation, protein synthesis, and energy availability and can be used to confirm protein and global metabolic impairment [ 33 ].
Protein intake and AA availability are key to maintaining protein synthesis in living organisms. Healthy individuals absorb AAs from the diet after protein digestion by pancreatic enzymes.
However, the pancreas uses large amounts of AAs and energy to produce digestive enzymes [ 10 ]. In addition, gut microbiota alterations and impaired intestinal function, including altered nutrient digestion and absorption, have been reported in patients with chronic disease [ 34 ]. These conditions lead to impaired AA digestion and absorption and, consequently, to reduced AA plasma levels that may become insufficient to maintaining protein synthesis and energy demand in HS patients [ 10 ].
In contrast, individual AAs derived from nutritional supplements are immediately available after absorption and transit into the bloodstream to be delivered to cells [ 35 ]. EAAs stimulate protein synthesis in both young and the elderly [ 36 ]. However, it has recently been shown that specific diets containing blends of individual EAAs in stoichiometric ratios are crucial for providing AAs for various metabolic needs, such as protein synthesis, mitochondrial biogenesis, and other important metabolic pathways crucial for cell life [ 6 , 37 , 38 ].
Clinical and experimental data suggest that oral supplements with specific individual EAA mixtures ensuring metabolic energy supply, administered traditionally, counteract protein disarrangement and cellular energy impairment without influencing renal function [ 40 , 41 , 42 , 43 ].
The clinical consequences of this is that the percentage of nitrogen and calories provided by diet should be calculated separately according to metabolic needs. Moreover, the amount of EAAs should be provided as a function of their intrinsic capacities to maintain proteins and body metabolism.
In addition, individual AAs should be provided so they are not rapidly absorbed, thus increasing their blood viability [ 44 ]. Taken together, these observations could explain why previous studies were unable to show any effects of simple total protein dietary supplementation on protein and energy metabolism in patients with chronic diseases [ 45 ]. Such findings support the indication that the elderly need increased EAA to stimulate muscle protein synthesis.
This also introduces the concept of evaluating protein AA composition protein quality [ 46 ]. Indeed, to maintain healthy muscles and bones, at least 30 g of high-quality protein and more importantly specific EAAs should be ingested at more than one meal. The effect of dietary administration of different EAAs blends has been actively investigated in the recent years [ 42 , 43 , 44 ]. Existing findings on the molecular pathways elicited by proteins and AA metabolism in chronic disease conditions could allow the development of therapeutic strategies to contrast metabolic impairment, especially in the elderly.
The evaluation of protein disarrangement deserves greater attention to manage chronic diseases, especially in old age see Box 1. Readily available and inexpensive anthropometric and blood parameters, such as TST, AMA, and albuminemia, can be obtained routinely at the bedside.
Additional research could unveil the causes of these conditions and monitor the outcome of specific therapeutic interventions. Both circulating i.
Not a MyNAP member yet? Register for a free account to start saving and receiving special member only perks. Both animal and plant proteins are made up of about 20 common amino acids. Amino acids are required for the synthesis of body protein and other important nitrogen-containing compounds, such as creatine, peptide hormones, and some neurotransmitters. Although allowances are expressed as protein, a the biological requirement is for amino acids. Proteins and other nitrogenous compounds are being degraded and resynthesized continuously.
Proteins are macro-molecules crucial for cell life, which are made up of amino acids AAs. In healthy people, protein synthesis and degradation are well balanced. However, in the presence of hypercatabolic stimulation i. The biochemical consequence of hyper-catabolism is protein disarrangement, clinically evident with signs such as sarcopenia, hypalbuminemia, anaemia, infection, and altered fluid compartmentation, etc. Hypercatabolic protein disarrangement HPD is often underestimated by clinicians, despite correlating with increased mortality, hospitalization, and morbidity quite independent of the primary disease.
If your institution subscribes to this resource, and you don't have a MyAccess Profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus. Please consult the latest official manual style if you have any questions regarding the format accuracy. The third part of our metabolism review focuses primarily on amino acids and proteins. Amino acids are used in many pathways beyond protein synthesis, including energy production and neurotransmitter synthesis.
In molecular biology , protein catabolism is the breakdown of proteins into amino acids and simple derivative compounds , for transport into the cell through the plasma membrane and ultimately for the polymerization into new proteins via the use of ribonucleic acids RNA and ribosomes. Protein catabolism, which is the breakdown of macromolecules , is essentially a digestion process. Protein catabolism is most commonly carried out by non-specific endo- and exo- proteases.
If your institution subscribes to this resource, and you don't have a MyAccess Profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus. Please consult the latest official manual style if you have any questions regarding the format accuracy. The third part of our metabolism review focuses primarily on amino acids and proteins. Amino acids are used in many pathways beyond protein synthesis, including energy production and neurotransmitter synthesis. Diseases in specific pathways do show up on Step 1, but overall, questions focus more on the function of each pathway and effects of diet on their function.
Twenty amino acid s, including nine that cannot be synthesized in humans and must be obtained through food, are involved in metabolism. Amino acids are the building blocks of proteins; some also function as or are synthesized into important molecules in the body such as neurotransmitters, hormones, pigments, and oxygen-carrying molecules. Each amino acid is further broken down into ammonia, carbon dioxide , and water. Disorders that affect the metabolism of amino acids include phenylketonuria, tyrosinemia, homocystinuria, non-ketotic hyperglycinemia, and maple syrup urine disease. These disorders are autosomal recessive, and all may be diagnosed by analyzing amino acid concentrations in body fluids.
If your institution subscribes to this resource, and you don't have a MyAccess Profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus. Please consult the latest official manual style if you have any questions regarding the format accuracy. The third part of our metabolism review focuses primarily on amino acids and proteins.
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