Is Methylation Important?
First of all, we should define methylation. Strictly speaking, a methyl group consists of a carbon atom with three hydrogen atoms attached to it, and this is typed CH3. It turns out that the addition of methyl groups to proteins is an important process both for synthesizing new types of proteins and for determining how certain proteins behave. Additionally, methyl groups can be added directly to the DNA molecule and this process can determine the way DNA is transcribed to RNA, a fundamental first step in the process of gene expression. This area of biology is extraordinarily complex because regulation of any gene, or modification of any particular protein or amino acid, is intricately related to a myriad of tightly and exquisitely regulated biological processes. Accordingly, there are many unknowns about the effects of methylation on a given human disease.
Presented below is a diagram that illustrates some aspects of methylation handling in our body. In this, one sees a listing of various amino acids of which methionine is important. Methionine contains a methyl group that is subsequently used in the process of methyl donation to many proteins and other molecules. You can follow this methyl group (listed as red and encircled) and see that it is transferred to a molecule called SAM (S-adenosyl-methionine). SAM is a very important carri
er molecule as it subsequently donates methyl groups to a host of biological reactions. SAM is ultimately recycled back to methionine, as indicated in the lower part of the diagram. In this process, it is metabolized to homocysteine and subsequently converted back to methionine by the addition, once again, of a methyl group. This methyl group is obtained from a folic acid-related molecule, 5-methyl-tetrahydro-folate. In this process of transfer of the methyl group, vitamin B12 is an important cofactor. Obviously, the production of various folate metabolites is dependent on dietary intake of folate.
I've listed on this diagram several approaches that theoretically could increase the availability of methyl groups in biological systems. Some of these are used as dietary supplements. For example, Betaine is a source of methyl groups and theoretically is available to methionine. Creatine may help to reduce depletion of SAM since the de novo synthesis of creatine consumes SAM. Folic acid can be taken orally and of course vitamin B12 can either be taken orally or by injection. I have also listed glutathione as a supplement but that is not particularly related to methylation; it a reducing agent that is one of a group of agents called antioxidants, a subject for another discussion on antioxidants.
What is the evidence that there is a methylation problem in autism? Tthere is no convincing human evidence to support such a theory. Since methylation can theorectically affect gene function or protein interaction in the brain, it has been hypothesized that a methylation defect might underlie the causation of autism. Alternatively, it has be theorized that treatment of autism could be helped by augmenting the availability of methy groups in the body. There have been some studies that measure various amino acids in the blood of autistic children and have attempted to correlate either low or high homocysteine and methionine levels with methylation handling (see James J, Am J Med Genet, 2006). These studies are preliminary,have not been very convincing, and have not been replicated. Genetic studies have not found evidence of abnormally methylated genes in autism.