SAM-e reactions that produce, consume, and regenerate SAM are called the SAM cycle. In the first step of this cycle, the SAM-dependent methylases (EC 2.1.1) that use SAM as a substrate produce S-adenosyl homocysteine as a product. This is hydrolysed to homocysteine and adenosine by S-adenosylhomocysteine hydrolase EC 220.127.116.11 and the homocysteine recycled back to methionine through transfer of a methyl group from 5-methyltetrahydrofolate, by one of the two classes of methionine synthases EC 18.104.22.168 or EC 22.214.171.124. This methionine can then be converted back to SAM, completing the cycle.
In the United States, SAM is sold as a nutritional supplement under the marketing name SAM-e (also spelled SAME or SAMe; pronounced "sam ee"). SAM is also marketed under the Gumbaral, Samyr, Adomet and Admethionine brand names as a prescription drug approved in Russia, Italy, and Germany. Some research has indicated that taking SAM on a regular basis may help fight depression,liver disease, and the pain of osteoarthritis. An authoritative report on SAMe is from the Agency for Healthcare Research and Quality (Dept Health and Human Services. Multiple clinical trials indicate benefits for depression, some liver conditions and osteoarthritis. All other indications are not yet proven.
Therapeutic use of SAM has increased as dietary supplements have gained in popularity, especially after the Dietary Supplement Health and Education Act was passed in 1994. This law allowed the distribution of SAM as dietary supplement, and therefore allowed it to bypass the regulatory requirements for drugs of the Food and Drug Administration (FDA). At first, a line of evidence suggested that abnormally low levels of endogenous SAM may play an important role in the development of Alzheimer's disease (AD) and that SAM may therefore have therapeutic potential in the treatment of AD (further research indicates this effect is likely due to Vitamin B12 deficiencies, which cause neurologic defects through one carbon transfers with folate). Severely low levels of SAM have been found in the cerebrospinal fluid and in all brain regions of AD patients examined.
SAM-e (S-adenosyl-methionine) is used to treat depression and joint pain. It is a prescription medication in European countries, but sold as a supplement in the U.S. where annual sales are close to $100 million. Our previous tests of SAMe supplements found that not all contained the listed amounts of this expensive ingredient. But the most recent testing identified ten products that contained their claimed amounts. SAM-e & Homocysteine: Once SAM-e donates its methyl group to choline, creatine, carnitine, DNA, tRNA, norepinephrine, and other compounds, it is transformed into S-adenosyl-homocysteine, (SAH). Under normal circumstances, homocysteine, in the presence of Vitamin B6, B12, and folic acid (SAM-e's main co-factors), will eventually be converted back into methionine, SAM-e, or cysteine, glutathione, and other useful substances. However, if adequate amounts of these vitamins are not present, SAM-e will not break down properly. As a consequence, the full benefits of SAM-e will not be obtained, and homocysteine may increase to unsafe levels.