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Burn hypermetabolism is characterized by an elevated metabolic rate, increased protein catabolism, and energy consumption. Hypermetabolism in severe burn patient could last several weeks or longer; it is one of the most significant reactions of homeostasis. In view of this, since the 1980s, the Burns Institute of the Southwest Hospital (BISH) at the Third Military Medical University (TMMU) has investigated the general trends and rules of energy expenditure, developed a formula to calculate calorie needs in Chinese adult burn victims and the relationships between energy expense and burn area, depth, phase, prognosis, putting forward a proposal that is different from the conventional ebb and flow phase, studied the proportion of energy expense among glucose, fat, and protein, and advanced a new theory, “enterogenous hypermetabolism” and its modulation [1–3].

The daily turnover of cellular proteins is very large, in the range of the protein contained in 1–1.5 kg of muscle. Consequently, even a small, persistent increase in the rate of protein degradation or decrease in protein synthesis will result in substantial loss of muscle mass and increased morbidity and mortality. Activation of protein degradation in the ubiquitin-proteasome system is the mechanism contributing to loss of muscle mass in kidney disease. Since other catabolic conditions also stimulate this system to cause loss of muscle mass, identification of activating signals is of intense interest. A complication of kidney disease, metabolic acidosis, activates the system in muscle by a process that requires glucocorticoids. The influence of inflammatory cytokines on this system in muscle is more complicated, as evidence indicates that cytokines suppress the system; but again, glucocorticoids block the effect of cytokines to slow protein breakdown in the system. New information identifying mechanisms that activate protein breakdown and the rebuilding of muscle fibers will lead to therapies that successfully prevent the loss of muscle mass in kidney and other catabolic illnesses.

13 samples of Littorina saxatilis were collected from a Maine shore on an approximately monthly basis and analysed for soluble uric acid concentration. This concentration varied significantly, with summer concentrations as much as 6 times higher than winter concentrations. While it may be that the accumulation of uric acid in summer is related to desiccation, we suggest that it is more likely to be a result of increased protein catabolism.

In living cells, proteins are generally unstable compounds, and are continually broken down and resynthesized. Proteins are easily denatured and even the most robust of them lose their activity over time. The needs of many cells vary from minute to minute and cells of all organisms adapt to this by changing, to varying extents, the proteins which they make and hence the functions which they are able to perform.

The classical definition of essential amino acids is those α-amino acids whose carbon skeleton cannot be synthesized in the human (animal) body (1). Over the past 15 years it has become apparent that the simple division of 20 amino acids for which there exists a t-RNA into essential and non-essential was too simplistic (2). A newer terminology has been created, which will be used in the remainder of this review, namely, indispensable (which is equivalent to essential), conditionally indispensable and dispensable (which is equivalent to non-essential). The concept of conditionally indispensable is particularly important when considering the amino acid needs of infants. Optimal growth of lean tissue requires that an appropriate mixture of all 20 amino acids and sufficient non-protein energy is present to optimize net protein synthesis. Interestingly, Duffy et al. (3) in parenterally fed very low birth weight neonates and Fuller (4) in piglets have shown that an improved balance of amino acid intake results in enhanced net protein deposition by reducing endogenous protein breakdown.

The quantitative autoradiographic L-[1-14C]leucine method for the determination of regional rates of cerebral protein synthesis in vivo takes into account recycling of unlabeled leucine derived from protein degradation into the precursor pool for protein synthesis. We have evaluated the degree of recycling in whole brain by measuring the ratio of the apparent steady state leucine specific activity in the precursor pool (tRNA-bound leucine) to that in arterial plasma. In normal, conscious, adult rats this ratio (λWB) equals 0.58 indicating that 42% of leucine in the precursor amino acid pool is derived from protein breakdown. Evaluation of λi in local brain regions indicates that the degree of recycling does vary regionally. Local rates of leucine incorporation into protein determined with the quantitative autoradiographic technique and regional values of λi ranged from 11.0 in hypoglossal nucleus to 3.8 nmol/g/min in white matter. The average rate in the brain as a whole was found to be 6.1 nmol/g/min. Results of our studies of regeneration in the hypoglossal nucleus and plasticity in the developing monkey visual system suggest that chronic changes in functional activity in a pathway are more likely than acute changes to result in effects on rates of protein synthesis in structures of the pathway.

Capítulo en: B.M. Mazoyer; W.D: Heiss; D. Comar (eds.). PET Studies on Amino Acid Metabolism and Protein Synthesis : Proceedings of a Workshop held in Lyon, France, within the framework of the European Community Medical and Public Health Research. Dordrecht: Springer, 1993, p.53-68. (Developments in Nuclear Medicine ; 23). ISBN 978-94-010-4706-7. ISBN 978-94-011-1620-6. DOI 10.1007/978-94-011-1620-6_4, 1) Total brain radioactivity was found to be regionally correlated (r = 0.97) with radioactivity incorporated into proteins following a bolus injection of [14C-methyl]methionine. This suggests that regional differences in total label accumulation correspond to differences in the incorporation of label into proteins. 2) Under steady-state conditions (i.e., during continuous infusion of [14C-methyl]methionine), regional brain specific activity (SA) was found to be lower than the plasma SA. Brain SA was diluted by an endogenous source of free methionine likely to be from protein breakdown. Assuming that all endogenous brain methionine can contribute to protein synthesis, measuring labelled methionine incorporation (without accounting for tissue SA), would lead to underestimated rates. 3) In contrast to these results, similar studies carried out on the rat heart have shown a ratio of heart to plasma SA equivalent to unity. According to this, methionine recycling did not became apparent in the heart during the experimental time and under our experimental conditions.

There is a paucity of information concerning the metabolism of the small intestine in the presence of bacterial endotoxins. The effect Escherichia coli (055:B5) endotoxin (50 ng/ml) on nitrogen metabolism was studied in isolated rat enterocytes incubated in the presence or absence of glutamine and/or glucose as energy substrates.

The normal liver is responsible for several functions indispensable for normal amino acid metabolism and homeostasis. These functions include the degradation of several amino acids for gluconeogenesis, conversion of amino acids to urea and glutamate, formation of several non-essential amino acids or enzymes, and the removal of amino acids from plasma1. Regulation of plasma amino acid concentrations appears important to body homeostasis, normal organ function, protein metabolism and to prevent metabolic acidosis. The gluconeogenetic and catabolic enzyme pathways are essential to this effort.

This chapter covers the methods available for the synthesis of amino acids, and refers the reader to other sections of this book where complementary coverage has been provided. No attempt has been made to cover large-scale fermentative production of some of the protein amino acids [1] but due emphasis is given in this chapter to the use of protein amino acids as starting materials for the synthesis of other α-amino acids.

Abnormal patterns of plasma amino acids are common in patients with liver disease1–5 and can be corrected by the administration of both branched-chain enriched amino-acid solutions6–9 or the three branched-chain amino acids (BCAA) alone10,11. These solutions have been reported as valuable in hepatic encephalopathy6,7,9 in restoring the profile of plasma amino acids towards normal6,8–11 and improving nitrogen balance6,7,11. There is also evidence that nitrogen losses are reduced following injury in patients or animals with normal liver function given branched-chain amino acids. The effect recorded appears to be out of proportion to the nitrogen content of the infusions13. O’Keefe et al.15 investigated the effect of oral BCAA on body protein metabolism in liver disease and reported that turnover, breakdown and synthesis were diminished.

Weakness and tiring easily are the most common symptoms of surgical convalescence. This response is more severe and prolonged than the associated bed-rest and decreased nutrition can account for. A prominent feature of acute surgical catabolism is an obligatory negative nitrogen balance, associated with protein breakdown. Despite the repeated confirmation of these findings since the first reports in 1930, the underlying mechanism and physiological significance remains obscure. The observed clinical weakness and fatigue may be the result of the negative nitrogen balance which is largely due to the breakdown of muscle protein.

Patients with chronic renal failure display a variety of metabolic and nutritional abnormalities and a large proportion of the patients demonstrate signs of protein-energy malnutrition [1–20]. This may be a consequence of multiple factors including disturbances in protein and energy metabolism, hormonal derangements, infections and other superimposed illnesses, and poor food intake because of anorexia, nausea and vomiting, caused by uremic toxicity. With maintenance dialysis therapy, some of these factors, but far from all, can be partly or fully corrected. On the other hand, metabolic and nutritional problems are caused by the method of dialysis. For example, the hemodialysis procedure per se may induce protein catabolism [8, 15, 16], peritoneal dialysis is associated with large protein losses into the dialysate [18, 19], and both dialysis methods are associated with dialytic losses of amino acids, vitamins, and other essential small solutes [20]. Futhermore, peritoneal dialysis is associated with absorption of large quantities of glucose from the dialysate.

The amino acid incorporation into the soluble proteins of normal old human lenses was studied. In the presence of cyclic AMP and a phosphodiesterase inhibitor this incorporation could be stimulated.

The burn patient has become the classic experimental model for the study of hypermetabolism and the catabolic state. Multiple investigators have documented increases of 50–100% over normal basal metabolic rates in patients with major cutaneous injuries, a situation that indicates special concern for the provision of adequate nutritional support.

Patients with acute renal failure have widely varying metabolic and nutritional states. Some patients have no evidence of negative protein balance, and they have normal plasma electrolyte concentrations and fluid and acid-base status. In general, these patients have no severely catabolic underlying illnesses. These patients are usually not oliguric, and the cause of their renal failure is typically an isolated non-catabolic event, such as a nephrotoxic reaction to a drug. On the other hand, most patients with documented acute renal failure have some degree of net protein catabolism and have altered fluid, electrolyte, or acid-base status1,2. These patients often have positive water balance, hyperkalaemia, hyperphosphataemia, hypocalcaemia, azotaemia, hyperuricaemia, and metabolic acidosis with a large anion gap.

Protein malnutrition is common in uraemia. Protein synthesis is probably reduced but protein breakdown is not increased at least under basal conditions. The reduction in protein synthesis may be due to a direct effect of an unidentified uraemic toxin(s) but, in addition, the adaptation to altered energy metabolism may reduce protein synthesis by increasing branch chain amino acid oxidation with a consequent reduction in the extracellular and intracellular pools of branch chain amino and keto acids. Lowering nitrogen toxicity by reducing nitrogen intake and supplementing with essential amino acids or keto acids may improve growth in some children.

Amino acids are found in living organisms in both their free forms and bound by amide linkages in peptides and proteins. The diversity of structure observed in the free amino acids (several hundred are known) contrasts with the limited array of L-α-amino acids which are found in proteins and the peptides of higher organisms such as the mammals. The peptides of lower organisms, e.g. fungi and bacteria, are intermediate in the variety of their amino acids; cyclic structures, D-residues, and αβ-unsaturated residues are frequent components as well as α-hydroxy acids and non-protein amino acids.

Before considering the feeding of patients with severe illness, it is im­portant to have an understanding of the physiological changes which are associated with starvation and illness, for these affect nutritional requirements and determine the design of appropriate diets.

Contemporary concerns about nutrition in renal failure derive from the development of artificial organs. When dialysis was used initially, nutritional management was limited to a daily intravenous infusion of 100g glucose. This amount maximally suppressed protein catabolism in fasting normal subjects. As solute and fluid loads can be more effectively removed with the newly developed, highly porous filtration membranes (e. g. solutes with mass of 10,000 daltons), there is increasing concern for maintaining adequate nutrition since protein and energy malnutrition and wasting have been noted in every nutritional survey of maintenance dialysis patients, affecting at least one-third of this population. The nutritional state generally deteriorates with time and home dialysis patients seem to do better than in-center patients (1). Fortunately, the use of short time, high flux hemodialysis does not appear to cause any additional adverse nutritional consequences over a 6-month period (2).