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What are amino acids?

Apart from being the building blocks of proteins, many amino acids are indispensable for certain vital functions or have specific functions of their own. They can function as neurotransmitters, as precursors for neurotransmitters and other important metabolites, including crucial oligo- and poly- peptides, as a stimulus for hormonal release, and in inter -organ nitrogen transport and nitrogen excretion. Consequently, manipulation of free amino acid levels by dietary or topical supplementation may support and modulate these specific functions.

Concentration and function of amino acids

Many amino acids have specific functions or support specific functions by serving as precursors or substrates for reactions in which vital end products are produced. The availability of amino acids to serve these purposes is determined by the rate at which they are released into the plasma and other pools in which these reactions take place, as well as by the rate of disappearance through excretion, protein synthesis, or conversion to other amino acids. The rate of this release, referred to as amino acid flux, is determined by the breakdown of (dietary) proteins or the conversion from other amino acids.

Increased demand for one or more amino acids generally leads to an increased flux of the required amino acids across specific organs. Since it is the flux of an amino acid that determines its availability for metabolic processes, the flux is far more important for maintenance of specific functions than the plasma concentration. In fact it is striking that fluxes of some amino acids can double without significantly affecting plasma levels despite the fact that the plasma pool may be quantitatively negligible compared to the flux per hour.

Plasma amino acid concentrations must therefore be subject to strong regulatory mechanisms. Increased demand and utilization of a specific amino acid may lead to decreased plasma and tissue concentrations, which may act as a signal to increase flux. Thus, a low plasma concentration in itself does not necessarily imply that the supply of the amino acid in question is inadequate, but it may indicate that there is increased turnover of the amino acid and that deficiencies may result when dietary or endogenous supply is inadequate.

Other factors determining amino acid concentration are induction of enzymes and stimulation or blocking of specific amino acid transporters affecting the exchange and distribution of amino acids between different compartments. The regulation of plasma and tissue concentrations of specific amino acids may also be executed by the fact that release of the amino acid by an organ (e.g., muscle) and the uptake of that amino acid by another organ (e.g. liver) are subject to a highly integrated network including the action of cytokines and other hormones.

By repeated conversion of one amino acid to another, metabolic pathways arise by which the carbon backbone of a single amino acid can pass through a succession of different amino acids. Because of this interconvertibility, groups of amino acids rather than one specific amino acid contribute to specific functions. Apart from the rate at which these amino acids interconvert, the rate at which they gain access to the tissue where the specific end products exert their functions is also an important determinant of deficiencies of amino acids.

Amino acids deficiencies and supplements

In many diseases and during undernutrition diminished turnover of amino acids can occur. These deficiencies may concern specific amino acids in certain diseases or a more generalised amino acid deficiency. The resulting functional deficits can contribute to the symptoms, severity, and progress of the disease. In some instances these deficits can be coun teracted by simple supplementation of the deficient amino acids.

Amino acid supplementation is also applied to enhance turnover and improve amino acid function in non-deficient patients. However, amino acid supplementation in non-deficient states does not necessarily lead to an increased function since the organism utilizes what is programed by regulating hormones and cytokines. An additional factor to consider is that metabolic processes can be subject to counter -regulatory feedback mechanisms.

Some important metabolic processes served by a specific amino acid require only a marginal part of the total flux of that amino acid. The question may be raised whether true shortages may arise in such pathways, and supplemented amino acids may be disposed of in pathways other than those serving to improve a specific function.

Table 1. Specific functions of amino acids and their intermediate products

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Assessing the function of amino acids

The effectiveness of amino acid supplementation, particularly with respect to clinical effectiveness, can be assessed at four levels.

  • The intervention should lead to an increased local or systemic concentration of the amino acid in question. The conversion of amino acids in (interorgan) metabolic pathways can lead to an increase in the levels of amino acids other than the one supplemented, increasing or mediating its functionality. Alternatively, supplementation of one amino acid may decrease the uptake of other amino acids because they compete for a common transporter.
  • The metabolic process for which the supplemented amino acid forms the substrate should be stimulated or unregulated by this increased amino acid availability.
  • This enhanced metabolic activity must lead to physiological changes.
  • These changes must be clinically effective in a desirable fashion.
SOURCES
  •   Guide to Nutritional Supplements (2009) Caballero, B.
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