Zinpro has been in this business for almost 50 years, and throughout this time our chemists have been researching how to make the best organic trace mineral. And we’ve discovered five essential factors that are required to have a successful performance mineral product.
This may seem like a large list of requirements for an organic trace mineral, and you might be wondering if it’s REALLY necessary to have all five. Yes, you really need all five factors, and as I go through this presentation, I’m going to explain why.
1.
2. 2-7
3. phytic acid, humic acid, tannic acid
4. The COMPLEX is absorbed from GI
5.
So through our decades of research we’ve found that you need five essential factors to have a successful performance mineral product. You can’t have one or two of these…you need to have all five.
1st, the compound must be water soluble…
Now if the compound is soluble it also has to be stable at physiological pH’s or at pH 2.0 – 7.4.
If you have those two the compound also has to be strong or stable enough to protect itself from chelating agents in the diet. So that those compounds can’t take the metal away from our complex and keep it from the animal.
Now if the complex, is soluble, stable at physiological pH and strong enough to protect itself it also needs to be absorbable from the GI…
…and finally the fifth factors…THE COMPLEX must result in the increased availability of the metal and the amino acid to the animal.
We took those five essential factors and used them to design our compounds…
WHERE IN THE INTESTINE IS IT ABSORBED….what is the pH at the various points in the digestion process.
What they have in common is that the amino acid backbone is able to form a five membered ring with the zinc ion; the acid hydroxyl bites into the zinc atom while the lone pair of electrons on the terminal amine stabilizes the ring. This ring in integral to the success of our product. The five-membered ring is favored in nature which means it forms easily, and it’s also quite stable.
Five membered ring has optimized ring strain
Zinpro uses amino acids as our organic ligands. Here are the structures of our two main products. Our products bind one methionine molecule, for our Zinpro classic line, or one of a mixture of amino acids for our Availa line, with one metal ion. But what they have in common is the five-membered ring system, formed by the acid hydroxyl digging in to the Zinc atom and the lone pair of the terminal amine stabilizing the ring. This ring in integral to the success of our product. The five-membered is favored in nature which means it forms easily, and it’s also quite stable.
The side chain of the amino acid is also important for the success of our product and is used to deliver the trace mineral to the animal.
You’ll also notice that each molecule is associated with a counter ion. The type of ion is different for different products but it imparts a slight salt character to our molecules which INCREASES the solubility of our product…in fact it makes it much more soluble that methionine alone.
An organic trace mineral is a trace mineral with an organic group attached to it. Not organic like organic produce, but in the chemical sense, a carbon-based group is attached. So to use some of our own products as an example (gotta get in those product plugs!), Zinpro uses amino acids as an organic ligand. Here is the structure Zinpro Classic, a zinc atom complexed with a methionine molecule, and our Availa Zinc, a zinc atom complexed with one of a mixture of amino acids.
These are our two main products. What they have in common is the five-membered ring system. This ring in integral to the success of our product. The five-membered is favored in nature which means it forms easily, and it’s also quite stable.
You’ll also notice that each molecule is associated with a counter ion. The type of ion is different for different products but it imparts a slight salt character to our molecules which INCREASES the solubility of our product…in fact it makes it much more soluble that methionine alone.
These are our two main products. The Zinpro Line uses the amino acid methionine and the Availa Zn uses a mixture of amino acids. What they all have in common is the five membered ring system. This ring in integral to the success of our product.
1:10,000 for logK = 4
1:10,000,000 for logK = 7
880
Straight carboxylic acids are all around 1….
Organic salt, readily dissociates even at neutral pH, very weak associations, will fall apart when it hits the stomach acid.
Propionic acid = Kemin pdt.
Zinc shuttle in enterocyte is ZnT7
There is already a system in place that animals use for absorbing inorganic trace minerals. For example, here is the zinc pathway. Zinc in the diet is absorbed in the small intestine when a zinc ion meets a zinc transporter. It is then taken through the enterocyte by a chaperone protein to another transporter on the basal side and pumped into circulation.
Once enough zinc builds up within the circulation, a signal is sent to the enterocyte to start producing a protein called metallothionine. Metallothionine is part of a system that helps to prevent metal poisoning. It steals zinc away from the chaperone proteins and sequesters it within the enterocytes until the cells are sloughed away and replaced.
Metallothionine expression can also be triggered by other metals in the diet, including calcium, copper, and iron. These antagonistic metals are also able to interfere with zinc absorption in the intestine by interfering with the inorganic metal transporter. Dietary chelators in the intestine can prevent zinc uptake by trapping the metal before it can reach a transporter.
An important thing to keep in mind about the inorganic transport pathway is that it is saturable. After a certain point, you will no longer see increasing benefits to the animal when increasing the inorganic metal supplementation.
Metallothionine used in inorganic metal absorption; upregulated by Zn uptake.
What we don’t know is when our complex gives up the zinc. The does it give it up in the epithelial cells or in the circulation….is it absorbed into the circulation intact or is absorbed onto the critical enzymes in the intestinal cells.
When the absorption of inorganic zinc is prevented by dietary chelators, other metals, metallothionine activity, and the saturable nature of this transport pathway, an animal may have difficulty getting all of the trace minerals it needs. The amino acid ligand of our Zinpro complexes allow us to use a different route to deliver metals to the animal: the amino acid transporter.
The amino acid transporters recognize the sidechain groups of amino acids, draw them into the intestinal cells, and then release them into the blood stream on the other side.
Since our complex is an amino acid attached to a metal, we’re able to use the amino acid transporters, bypassing the inorganic metal transport systems, and getting more mineral into circulation.
Of course when Dr. Monem first designed our Zinc-Methionine complex he was hoping that the molecule would be picked up by the amino acid transporters, but he didn’t know for sure, just that the products worked. More recently, we have actually been able to study our complexes at the cellular level.
…And then the absorption of the compound into circulation.
Using this assay, we investigated the first step of this process: uptake into cells.
So, we know that Zinpro performance minerals get into enterocytes, and then into circulation. But how are our complexes getting into cells?
I mentioned before that antagonistic metals and dietary chelators can prevent zinc uptake. We were able to recreate this effect in human enterocytes.
This serves as further validation that our Zinpro complexes are not using the inorganic transport system where antagonistic metals can prevent zinc uptake.
Fig 2a
We also see a difference in actual animals. When lambs are fed either inorganic zinc or our Zinpro classic zinc-methionine, there is a clear difference in zinc metabolism. Both zinc sources lead to zinc excretion in feces and urine, but our Zinpro zinc shows significantly higher retention within the animal, meaning that it is sticking around longer for the animal to use.
Absorbance is different from inorganic, doesn’t COMPETE with inorganic, allows for synergistic effects.
Rescaling the value retained, still significant.
Study: 1 & 2 ZINPRO® zinc methionine; Spears, 1989. J. Anim. Sci. 67:835
Study: 3 & 4 ZINPRO zinc methionine; Data from baseline and repletion periods only, not entire trial; Nockels et al., 1993. J. Anim. Sci. 71:2539
Study: 5 & 6 CuPLEX® copper lysine; Data from baseline and repletion periods, not entire trial; Nockels et al., 1993. J. Anim. Sci. 71:2539
Study: 7 MANPRO® manganese methionine; Weiss and Socha, 2005. J. Dairy Sci. 88:2517
Study: 8 Availa®Cu copper amino acid complex; Bowen, 1998. Doctoral Thesis
Study: 9, 11, 12, & 13 ProPath ® Zn zinc amino acid complex; Lee et al., 2022. Trans. Anim. Sci. 6:1
Study: 10 ZINPRO zinc methionine; VanValin et al., 2018. J. Anim. Sci. 96:25336
