Pyridoxamine – The most potent Glycosylation inhibitor

Pyridoxamine is one of three different naturally occurring forms of vitamin B6, the other two being pyridoxal and pyridoxine. All three of these vitamin B6 compounds are important to us. They are converted in the body into the biologically active form of B6 called pyridoxal 5-phospate (more commonly referred to as PLP or P5P) and are used in many different pathways. Although the rarest form of these B6 compounds to be found as a supplement (perhaps due to its relatively expensive cost per kilo), pyridoxamine is the most potent. Indeed, when you are talking about potency, pyridoxamine is the most potent natural substance available when it comes to inhibiting a process known as glycosylation.

Glycosylation (sometimes called cross linking) describes the biochemical reaction that occurs when sugar (normally in the form of glucose), is added to protein or lipid molecules. The process is controlled by enzymes and occurs at defined sites on the target molecule. Glycosylation is required for the molecule to function correctly.

However, whilst glycosylation is a controlled process occurring only at specific sites, the binding of sugar molecules to proteins also happens every day during normal bodily metabolism, on a haphazard basis. This process is called glycation and impairs the functioning of biomolecules. Sometimes glycation is referred to as “non-enzymatic glycosylation”.

The initial product of the glycation/glycosylation process is called a Schiff base. The Schiff base spontaneously rearranges itself into an Amadori product. At this stage the process is still reversible. A cascade of further chemical reactions then occurs with Amadori products undergoing dehydration and rearrangement to form cross-links between neighbouring proteins and DNA molecules. Ultimately, the process results in the formation of advanced glycation (or glycosylation) end products – usually termed AGEs.

Why is this important? Well, although scientists have still not yet been able to answer the 64 thousand dollar question of why we age in the way we do, we do now know that glycosylation and glycation play important parts in the aging process. Even from the earliest stages of embryonic development, our bodies are constantly forming AGEs. Unfortunately, our bodies cannot get rid of AGEs quickly so, over the years, a build of AGEs occurs. Although some AGEs are benign, many of them are far more reactive than the sugars that they were originally derived from which can lead to significant damage in long lived cells and proteins. And the more AGEs there are, the higher the incidence of aging disorders such as cataracts, hardened skin, tough collagen, Alzheimer’s Disease and cancer.

Cardiovascular diseases are also affected by glycosylation/glycation. For example, AGEs can modify LDL cholesterol (the so called “bad cholesterol”) in such a way that it can become easily oxidised. It’s the oxidation of cholesterol that causes it to become sticky and be deposited on blood vessel walls which, over time can lead to atherosclerosis – the root cause of various cardiovascular diseases such as angina, heart attack and stroke. The epithelial cells of blood vessels are also damaged directly by glycation and this damage is also implicated in atherosclerosis. As well as the above, glycation can cause the collagen in blood vessel walls to stiffen and weaken which can lead to hypertension (high blood pressure).

Diabetics are particularly affected by AGEs. The rate of formation of AGEs although constant, is usually slow unless you are diabetic. Glycation and glycosylation are fuelled by glucose which is available in greater amounts in diabetics. This leads to a noticeable increase in the formation rate of AGEs.

As mentioned above, the glycosylation/glycation process progresses through various different stages before AGEs are formed. Although there a number of excellent anti-glycators available that work well to prevent early stage glycosylation/glycation, these anti-glycators are not so effective in later stages of the process. Pyridoxamine, on the other hand, is at its most effective in post- or late-stage glycosylation/glycation.

Pyridoxamine is also known to have the ability to enhance glucose metabolism and quench toxic free radicals, in addition to its impressive ability to help block the formation of AGEs. With all these benefits, pyridoxamine can effectively help to support healthy nerve, eye, cardiovascular and kidney function and maybe a key to helping us stay healthier for longer.