SPONSORED BY ALLTECH

By RICHARD MURPHY Ph.D.

WHEN trying to compare organic trace minerals (OTMs) on the basis of "which is best under this set of conditions," one really needs to consider many different factors.

However, it can be useful to compare them using what are known as stability constants (beta). These values represent a useful way to determine the relative strength of the interaction between a mineral and the bonding group (ligand) in an organic trace mineral.

In general terms, the greater the value of the stability constant then the greater the proportion of bound mineral that is present relative to free ligand ([L]) or free metal ([M]) at a given pH. The stability constants for a range of ligands including single amino acids, dipeptides, tripeptides, etc., can be readily obtained from the National Institute of Standards & Technology stability constants database, which calculates the value taking into account relative pH, ionic strength, temperature, ligand type, ligand and metal concentrations.

Typically, stability constant data are presented in log values but can easily be transformed into relative terms making data interpretation easier.

Consider the data in Table 1, which gives the stability constants for a range of ligands when complexed with copper under the same physiological conditions. The molecular weight of each bonding group is also given to provide size comparisons.

What this indicates is that the type of bonding group is the main determinant in influencing the relative stability of a given chelate and that the size of the bonding group is of less importance. In this case, smaller is certainly not better, particularly when more complex dipeptides are compared to simple amino acids such as glycine.

Interestingly, when one compares the stability constants for methionine and that of the artificial derivative, methionine hydroxy analogue (MHA), one can appreciate the destabilizing effect that modifying the amino acid has. The relative stability dramatically decreases, and this shows how even subtle changes in the structure of a bonding group can dramatically affect its ability to form stable organic mineral chelates.

Table 2 examines what happens if the amino acid sequence in a peptide is manipulated, and it is obvious that the sequence and position of amino acids in a peptide will greatly affect the relative stability of a chelate.

The substitution of a histidine into the tripeptide Gly-Gly-Gly to yield Gly-Gly-His, for instance, enhances the relative stability of the peptide 270 fold. Furthermore, changing the position of this histidine within the tripeptide sequence (to form Gly-His-Gly) can result in an even greater enhancement of the relative stability. In practical terms, simple changes in the configuration of amino acids in this tripeptide can result in dramatic improvements in the relative stability's of chelates formed using them. Ultimately, this means a greater proportion of bound mineral relative to free mineral and peptide when compared under the same relative conditions.

Essentially, mineral chelate stability can be significantly influenced by not only the type of amino acid but also the configuration of amino acids in a peptide sequence. It's worth reiterating that ligand size isn't of paramount importance -- the type of ligand is.

So what does this mean in practical terms?

This type of information can be used to have profound impacts on OTM production. For instance, by manipulating the hydrolysis of complex protein sources into "optimized" peptide hydrolysates, one can also maximize the relative stability of the subsequent OTM. In essence, the stability of an OTM can be significantly affected or improved by the production method employed.

In practical terms, one can use these values to compare individual organic mineral products on the basis of which is more stable under acidic conditions such as found in the stomach. Obviously, the more stable the product; the more mineral will be delivered in protected or bound form to the absorption sites in the intestines and by comparing the relative stabilities of different ligands or bonding groups, we can make a decision as to the likelihood of which will deliver more mineral in a bound neutral form to the sites of absorption in the intestines.

Bonding groups with reduced relative stability will mean that any mineral complex or chelate formed with them will readily dissociate into the free mineral (ionic) form and the free bonding group. As a consequence of this dissociation, the charged mineral can react with negatively charged plant components, such as phytic acid, which may be present in the gastrointestinal tract, or worse still will form so-called hydroxides upon reaching the more alkaline environment in the intestines. This can lead to the phenomenon of pH induced hydroxypolymerization and result in precipitation of the mineral and thus lead to a very significant reduction in bioavailability. Additionally, the likelihood of these charged minerals inhibiting enzymes is high and in the case of Cu2+ and Fe2+ can cause oxidative stress via the Fenton reaction and as such increase the requirement for not only vitamin E but also for selenium and vitamin C which are required for vitamin E recycling.

Essentially, bonding groups with low relative stability actually reduce the effectiveness of the product to that of the corresponding inorganic salt.

Organic mineral supplements must remain biologically available and, clearly, the mineral must not be associated with ligands where the stability constant is so high that the mineral cannot be removed from the bonding group. A good example of such a bonding group is EDTA whose chelating or mineral-binding ability is so great that any chelated mineral is rendered biologically unavailable and is in essence of no use in animal nutrition.

An examination of Table 1 also indicates that in many cases chelates formed using peptides as the bonding group or ligand are more stable than single amino acids and in many respects are more suitable in terms of delivering mineral to the sites of absorption in the intestine due to their reduced dissociation in an acidic environment.

Even though the chemistry behind organic trace minerals can be quite complex, the use of stability constant values can provide a significant amount of information concerning the relative stabilities and suitabilities of different bonding groups. This enables the user to make an informed decision as to the suitability of individual OTM products. The use of such data has shown that size doesn't matter -- the type and configuration of a bonding group is of far greater importance.

Final thoughts

Despite the confusion and often contradictory information that exists, mineral chelation is a relatively straightforward process governed by some fundamental chemistry basics. By carefully considering factors important in mineral chelation, one can begin to distinguish between the products on the basis of relative stability and thus biological bioavailability.