also known as holotranscobalamin
Methionine Metabolism Profile (NutriPATH)
Methylation is a process where certain nutrients called ‘methyl donors’ are added to specific elements of DNA, our gene markers and proteins that keep them physiologically active. Methylation is a major pathway to focus on in understanding autoimmune and neurological diseases such as multiple sclerosis, seizure disorders, dementia, chronic fatigue syndrome, lupus, depression, anxiety and autism spectrum disorders. Methylation is responsible for making, maintaining and repairing DNA.
The methylation cycle is a biochemical pathway that manages or contributes to a wide range of biochemical functions: detoxification, supporting DNA (turning genes on and off), producing energy, reducing inflammation, synthesising neurotransmitters, homocysteine metabolism, protein methylation, phase 2 liver detoxification and supporting immune function. Inadequate methylation capacity can lead to birth defects, depression, cognitive decline, and cancer. Impaired methylation has even been associated with autism. Support of methylation markers has been associated with rapid return of speech, improvement of behaviour in ADD and ADHD spectrums.
Methionine is an amino acid necessary for utilisation of methyl groups from the folate cycle and balance homocysteine levels. Methionine synthase (MTR) requires vitamin B12 and an enzyme, methionine synthase reductase, which is produced from the MTRR gene. Homocysteine, a sulphur-containing amino acid, is a metabolite of the essential amino acid methionine, and exists at a critical biochemical intersection in the methionine cycle between (Sadenosylmethionine), the indispensable ubiquitous methyl donor, and vitamins B12 and folic acid. High blood levels of homocysteine signal a breakdown in this vital process, resulting in far-reaching biochemical consequences. The Methylation Cycle is a biochemical pathway that manages or contributes to a wide range of biochemical functions: detoxification, supporting DNA (turning genes on and off), producing energy, reducing inflammation, synthesising neurotransmitters, homocysteine metabolism, protein methylation, phase 2 liver detoxification and supporting immune function. Inadequate methylation capacity can lead to birth defects, depression, cognitive decline, and cancer. Impaired methylation has even been associated with autism. Support of methylation markers has been associated with rapid return of speech, improvement of behaviour in ADD and ADHD spectrums.
Conditions associated with impaired methionine and methylation defects:
Allergies, Diabetes, Autism, High folate supplementation, Cancer, Infertility, Pre-conception care, Chronic Fatigue Syndrome, Mental health disorders, Cognitive decline, Estrogen dominance, Cardiovascular disease, Schizophrenia.
Significant markers of methionine metabolism assessment:
SAMe (S-adenosylmethionine) - a synthetic form of a compound formed naturally in the body from the essential amino acid methionine and adenosine triphosphate (ATP), the energyproducing compound found in all cells in the body.
SAH (S-adenosyl Homocysteine) - amino acid derivative and modulator of the activated methyl cycle and cysteine biosynthesis and product of SAMe-dependant methylation of biological molecules, including DNA, RNA, histones and other proteins.
Vitamin B12 - essential for recycling homocysteine and the formation of methyl donors involved in cardiovascular function, sleep, blood cell formation, and nerve function.
Folate - a substrate and vitamin B12 is a coenzyme for the formation of MTHF that depends on the regeneration of THF, the parent compound in the homocysteine-to-methionine conversion.
Homocysteine - an amino acid associated with atherosclerosis that can become elevated when there is need for folate, vitamin B6 and/or vitamin B12.
Methionine - an amino acid necessary for utilisation of methyl-groups from the folate cycle and balance homocysteine levels.
Biomarkers in this category
7 biomarkers · optimal ranges shown
often referred to as SAH
commonly known as SAMe
The SAM/SAH ratio is commonly referred to as the “Methylation Index” in the literature and has well- documented clinical associations. Global methylation is dependent on two key factors: adequate SAM supply and SAH removal. The SAM/SAH ratio has been proposed to indicate the likelihood of hyper- or hypo-methylation. Overall, the SAM/SAH ratio is under tight homeostatic control. SAM levels remain fairly stable due to denovo synthesis and feedback mechanisms. Given this, alterations in the methylation index are more likely a result of SAH fluctuations. SAH is a potent inhibitor of methyltransferase reactions, which is likely why SAH elevations and a low methylation index are correlated with global hypo-methylation. Furthermore, poor homocysteine clearance contributes significantly to SAH elevations which provides insight into the relationship between these two analytes and cardiovascular disease. The SAM/SAH ratio is resistant to fluctuations in independent nutrients, given the interconnectedness of the pathways. SAM remains fairly stable due to de novo synthesis and the liver’s tight control over SAM levels. Therefore, is it more likely that SAH variability will lead to alterations in the methylation index. Methylation reactions become compromised with a decreased SAM/SAH ratio and as SAH levels become elevated. SAM/SAH ratio abnormalities should be addressed by ensuring adequate dietary methyl donor levels (i.e. methionine, SAM-e) and nutritional cofactors required for clearance of SAH and homocysteine (i.e. B6, B12, and folate). It is important to note that while the Methylation Panel does not directly measure DNA methylation, the SAM/SAH ratio has been shown to correlate with DNA methylation. Many environmental and lifestyle factors have been shown to affect DNA methylation which can turn on/off gene expression. Exposure to tobacco smoke, arsenic, benzene, radiation, lead, cadmium, nickel and asbestos are all tied to DNA methylation defects. Obesity, lack of physical activity, and shift work have also been shown to alter DNA and histone methylation, and thereby gene expression. Chronic alcohol use is another pertinent lifestyle factor to evaluate as it can cause malabsorption of key B-vitamins necessary for methylation.