S-Adenosylmethionine and Methylation

Methylation is involved in nearly every aspect of life. Proper DNA methylation is essential for normal embryonic development, and its dysregulation has been associated with various human diseases. SAM-e is required for cellular growth and repair and is the sole methyl donor for numerous methyl-transfer reactions in DNA, RNA, proteins, lipids, phospholipids, hormones and neurotransmitters. SAM-e provides the methyl group in the production of essential biomolecules including:

• Acetyl-L-Carnitine: Neuronutrient and membrane-transporting agent
• Epinephrine & adrenaline: Endogenous catecholamfine, stress hormone and neurotransmitter
• Phosphatidylcholine: important component of biological membranes
• Carnitine: Transporter of fatty acids into mitochondria
• Phosphocreatine: ATP reservoir
• Melatonin: Circadian rhythm modulator

SAM-e also plays an important role in the synthesis of polyamines using the aminopropylation pathway. SAM-e is first decarboxylated and the aminopropyl group transferred to putrescine to generate spermidine and spermine, which are both critical to cell growth, differentiation and stability of DNA and RNA.

Methylthioadenosine (MTA), the by-product of polyamine synthesis, is a powerful analgesic and anti-inflammatory agent. This may be, at least partially, responsible for the clinical benefits observed in the treatment of osteoarthritis, rheumatoid arthritis and fibromyalgia with SAM-e.

The transsulfuration pathway begins with S-adenosylhomocysteine (SAH), which is the residual structure following the transfer of a methyl group from SAM-e. Hydrolysis of SAH yields homocysteine, which is converted to cystathionine, cysteine, and finally to glutathione, the hepatocellular antioxidant and life-saving detoxification agent. Since dietary cysteine content is low, and up to 80% of dietary cysteine loses its sulfhydryl groups through the gastrointestinal tract, SAM-e is the main source of cysteine, the building block of glutathione.

SAM-e is claimed to be helpful for the following conditions:

• Depression
• Parkinson's disease
• Osteoarthritis symptoms
• Liver disease

• Attention deficit hyperactivity disorder (ADHD)
• Premenstrual syndrome (PMS)
• Premenstrual dysphoric disorder (PMDD)
• Chronic fatigue syndrome (CFS)
• Heart disease
• Defective intellectual performance
• Multiple sclerosis
• Dementia
• Alzheimer’s disease

Since SAM is an intrinsically unstable molecule, the determination of its concentration in various biological fluids and tissues has always been a challenging task. Defined as the ratio of SAM and SAH, methylation index is an effective way to evaluate the status and extent of methylation in humans and other organisms.