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Current Opinion in Clinical Nutrition & Metabolic Care:
doi: 10.1097/MCO.0b013e32834de431
PROTEIN, AMINO ACID METABOLISM AND THERAPY: Edited by Olav Rooyackers and John Brosnan

The importance of amino acids as independent metabolites, signalling molecules and as building blocks for protein

Brosnan, Johna; Rooyackers, Olavb

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aDepartment of Biochemistry, Memorial University of Newfoundland, St. John's, NL, Canada

bDepartment of Anesthesiology and Intensive Care, Clintec, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden

Correspondence to Olav Rooyackers, PhD, Department of Anesthesiology and Intensive Care, Clintec, Karolinska Institutet, Karolinska University Hospital, 141 86 Huddinge, Sweden. E-mail: olav.rooyackers@ki.se

We regard the amino acids as the most interesting of all nutrients. This follows from the variety of their side-chains which permits a remarkably versatile range of chemical reactions. It is hardly an accident that of the four known gaseous signalling agents (ethylene, nitric oxide, carbon monoxide and hydrogen sulphide), all but carbon monoxide are derived from amino acids. In addition, they are the building blocks of our proteins that make up the bulk of our lean body mass and are crucial for our bodily functions by their involvements in structure, metabolism (as enzymes) and as regulators (hormones, cytokines, signalling, etc.). The reviews in this issue of Current Opinion in Clinical Nutrition and Metabolic Care emphasize the variety and complexity of amino acids and proteins, together with their very direct relevance to human health.

Compelling epidemiological evidence for a relationship between plasma cysteine and BMI came originally from the Hordaland Homocysteine Study, a very large population-based study of approximately 18 000 men and women from Western Norway. However, the nature of the relationship was not immediately evident from the epidemiology. The review by Elborgagy et al. (pp. 49–57) explores this relationship in detail, both with regard to human studies and work with experimental animals. They provide strong evidence that elevated cysteine may be a direct cause of obesity, possibly acting via a redox mechanism. This novel interaction between a specific amino acid and lipid metabolism notably expands the repertoire of functions ascribed to these nutrients.

Phillips et al. (pp. 58–63) discuss the interaction between diet and exercise in bringing about net protein accretion in human skeletal muscle. They emphasize the importance of the timing of a protein-containing meal with respect to resistance exercise as a determinant of muscle protein synthesis. They also introduce the novel concept of an innate ‘muscle-full’ set-point that may set a ceiling on muscle protein synthesis that limits the action of such factors such as amino acid availability and anabolic humoral agents. It will be very important to discover the nature of this set-point and how it may be reset, as this could greatly facilitate improvements in net protein accretion in specific populations such as the elderly. Finally, the article by Phillips et al. (pp. 58–63) reminds us of how much more we know of muscle protein synthesis than of muscle protein breakdown, both with regard to mechanisms and quantitation.

Arginine has emerged as a fascinating amino acid. Indeed, the discovery of nitric oxide production from arginine may be regarded as one of the most extraordinary advances in the entire amino acid metabolism. The review by Morris (pp. 64–70) surveys a number of systemic arginine deficiency disorders, many of which are brought about by the release of erythrocyte arginase as a consequence of haemolysis. These disorders include both endothelial and T-cell dysfunction. The article highlights the utility of the global arginine bioavailability ratio [plasma arginine/(ornithine with citrulline)] as a useful biomarker of dysregulated arginine metabolism. It also reminds us of the limitations, in some circumstances, of nonhuman animal models, as neither rat nor mouse erythrocytes express arginase.

Branched chain amino acids and especially leucine have been investigated intensively for some time. During the last decade, it has become apparent that, of all the essential amino acids, leucine has the most potent signalling function. Leucine is a very potent stimulator of anabolic signalling pathways which can result in the net gain of mainly muscle protein. van Loon in a review (pp. 71–77) discussed recent findings of leucine as a pharmaconutrient for stimulating the gain of muscle in sports, diabetes and aging. Although acute studies show very convincing data on insulin secretion, anabolic signalling and muscle protein synthesis, long-term studies measuring actual muscle gain are less convincing.

Garibotto et al. (pp. 78–84) review new data on mechanisms for muscle wasting and cardiovascular complications in kidney failure. Several new and old concepts including methylation, arginine and especially the role of dimethylarginine, splanchnic protein turnover, the role of the proteasome system in muscle wasting, anabolic resistance and inflammation are discussed. Also, in kidney disease, leucine seems to play an important role and patients seem to have a resistance to leucine that can be overcome by giving more leucine. Inflammation and especially interleukin-6 plays a key role in the muscle wasting in kidney disease.

The role of cytokines in muscle loss in wasting disease is discussed in more detail by van Hall (pp. 85–91). Studies of tumor necrosis factor and interleukin-6 in healthy volunteers suggest that interleukin-6 is the more potent cytokine in inducing muscle wasting. Recent data also show that this might not be a direct effect, but is the result of an interleukin-6-induced reduction of amino acid levels and their availability for protein anabolism. Whether this interleukin-6 effect plays a role in wasting during severe illness can be questioned, because the changes in muscle protein turnover are not uniform in wasting diseases; some are characterized by a predominant decrease in protein synthesis, whereas others by an increased breakdown. van Hall discussed whether this could be due to the timing of the observations, particularly to differences in acute versus long-term changes.

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Conflicts of interest

There are no conflicts of interest.

© 2012 Lippincott Williams & Wilkins, Inc.

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