METHYL MAGIC


By Stanford Field
Summer 2004





Why is Methylation Important?

Methylation (the chemical transfer of a CH3- group) is an essential metabolic process that takes place in each of the cells of the body. Adequate methylation is required to attain a state of maximum physical and mental health. Conversely, lack of sufficient methylation is associated with poor health that is reflected in conditions such as heart disease, stroke, cancer, loss of memory, depression, arthritis, autoimmune diseases and aging.


Events Leading to the Discovery of the Importance of Methylation

Beginning in the mid-1800s, European pathologists discovered that blood clots formed layers on the internal lining of arteries. These layers became calcified into tough, hardened arteries. That disease was known as "arteriosclerosis."


In 1922, methionine was discovered and it was subsequently found to be essential for human life. In 1932, homocysteine was discovered, but its importance was not known.

In 1933, at the Massachusetts General Hospital, an eight year old boy with a rare inborn error of metabolism, died of a stroke. An autopsy showed he had advanced arteriosclerosis throughout his body, especially in the arteries of the heart, neck and legs. This provocative case could not be explained and was buried in the archives and forgotten.

In the 1950s, s-adenosylmethionine (SAM) was discovered at the National Institutes of Health in the United States. SAM was made from methionine, adenosine triphosphate (ATP) and liver enzymes. Subsequently, it was found that SAM effects nearly all methylation reactions in our bodies.

Then, in the 1960s in Ireland, the disease called "homocystinuria" was discovered. Homocystinuria is a metabolic disorder characterized by the dislocation of the lenses of the eyes, chronic fatigue, mental retardation, psychiatric disturbances and thromboembolic episodes. Thromboembolism occurs when a blood vessel is blocked by a clot (embolus) carried into the bloodstream from the site of formation of the clot (as in major surgery). A clot in the carotid arteries leading to the brain is serious because it causes death in the brain.

In homocystinuria, the liver is unable to dispose of homocysteine because of a genetic error in the enzyme that converts homocysteine into cystathionine which would then be metabolized to useful products. Thus, the homocysteine accumulates to levels that are 10-100 times "normal." Homocystine (the condensation of two homocysteine molecules) also accumulates and it is detected in the urine as the body desperately tries to rid itself of homocysteine.

Also in the 1960s, pathologists (most notably Kilmer McCulley, MD) in the United States began to connect the dots accumulated over the previous century. The eight year old boy had probably died of homocystinuria. Subsequent animal experiments verified it.

So, what makes homocysteine rise to unsafe levels (> 7 micromols per liter)? The answer lies in eating too much protein and not having the vitamin nutrients to methylate the homocysteine.

These discoveries gradually led to the realization that the transfer of a methyl group in many biochemical reactions was critical to achieving and maintaining good health.



The Good News: Methylation

Now that we know how some of the biochemical system works, we can take action to thwart the buildup of homocysteine and to encourage the formation of SAM. These reactions can be achieved with a source of methyl groups and other necessary biochemicals.


The details of those reactions and the magic of other methylations will be explained at the upcoming Smart Life Forum meeting. Bring your notebook and pen!

Best wishes for a healthy life,
Stanford Field



TOO LATE SCHMART is written by Stanford Field (BS chemical engineering, 1951) who has been avidly studying biochemistry and physiology, since 1993, with an aim of staying healthy despite the ever-increasing odds of age-related decline. This publication is written to the best of his ability, and it is intended to document any findings that may be useful to interested readers. The publication has neither profit nor political motives.

Summer 2004
All rights reserved.