Histadelia and Methylation. Part IV. What SAM does.

S-Adenosyl methionine (SAM) and Genetic Expression

1 By methylating DNA, regulates, usually suppressing, genetic expression, the process by which our genes cause RNA or specific proteins to be formed.
On the other hand, acetylation --by acetyl CoA, bolstered by folic acid-- typically promotes genetic expression.
So from moment to moment, the balance of SAM to folic acid at the chromatin strands, determines whether the chemical blue print encoded in the DNA will be used to form a new biomolecule, or will be suppressed.

2 Protects, repairs and stabilizes DNA.

Influence of SAM on dopamine, norepinephrine and serotonin activity

1 Functions as a natural reuptake inhibitor* for dopamine, norepinephrine and serotonin, increasing availability/activity of these neurotransmitters in the synapse.
Walsh explains that SAM inhibits reuptake epigenetically, by methylating (turning off) the neural membrane DNA which creates transporter proteins. If undermethylated, these transporters would remove neurotransmitters from the synapse, returning them to previous (pre-synaptic) neurons. Methylation by SAM, on the other hand, suppresses transporter creation, leading to an accumulation of dopamine, norepinephrine and serotonin in the synapse, thereby increasing neurotransmitter activity. (For more, see Nutrient Power by Dr. Walsh)

2 Influences tetrahydrobiopterin (BH4) synthesis of serotonin and dopamine: via methyl folate, which regulates BH4 production (click to enlarge).


3 Is used to recycle/inactivate norepinephrine, dopamine, epinephrine and serotonin.
  — With magnesium, forms COMT, which removes epinephrines and dopamine from the synapse. 
  — Regulates stress by metabolizing norepinephrine and epinephrine (adrenalin):  Methylates norepinephrine into epinephrine which, via COMT, is broken down into metanephrine.
  — With B5, metabolizes serotonin into melatonin (the hormone which triggers sleep).


SAM provides methyl to form proteins and lipids critical to mental function
1 Including melatonin, phosphatidyl choline, myelin, epinephrine, carnitine, Co-Q10, and creatine. 
2 Also helps form  cholesterol, steroids, calmodulin (which modulates calcium use) and polyamines (from histamine). Inactivates estrogen by (forming a methyl estrogen).

SAM is important in immune function (which repercusses on mental function)

1  In turning off DNA replication, helps defend against viruses which use our DNA to replicate. 
2 Important to cell-mediated (non-antibody) immune function.
3 Helps flag and remove toxins.
4  Helps regulate the formation of sulphur molecules, such as cysteine, glutathione, sulphate, and taurine. These are major antioxidant and detox agents.

See next post, The Transsulfuration Cycle.

Review the methylation diagram here

These diagrams provide a wider picture of cycle interactions (scroll down)

For info on the role of histadelia in bipolar disorder, see my book, Natural Healing for Bipolar Disorder