Methylation Profile; plasma
Normal metabolism of methionine is critical for cellular methylation of DNA, proteins and neurotransmitters. Aberrant methionine metabolism can occur in anyone at any age and can be associated with numerous health consequences including cardiovascular disease and cancer. The Methylation Profile provides a functional assessment of the phenotypic expression of common SNPs (MTHFR, MS, CBS) by evaluating the plasma levels of methionine, cysteine, SAM, SAH, homocysteine, adenose and cystathionine. It also provides the important "methylation index", a ratio of SAM to SAH.
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- Birth Defects
- Cardiovascular Disease
- Congenital Heart Disease
- Detoxification Impairment
- Down Syndrome
- General Health and Longevity
- Genetic Disorders
- Immune Dysfunction
- Neurodegenerative Diseases
- Nutritional Deficiencies
- Psychiatric Disorders
5 to 7 days
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Normal methionine metabolism is absolutely critical for methylation, transsulfuration and folate-dependent transmethylation. Abnormal metabolism of methionine can be found in anyone at any age. It is usually associated with genetic or nutritional deficiencies, aging and exposures to environmental toxicants. For example, lead can inhibit methyltransferase enzymes and transmethylation of homocysteine via inhibition of the enzyme methylene-tetrahydrofolate reductase (MTHFR).
Conditions associated with untreated, aberrant methionine metabolism include, but are not limited to:
- Abnormal neurotransmitter metabolism and psychiatric disorders such as schizophrenia and bipolar disorder
- Neurodegenerative diseases
- Dysregulation of nitric acid homeostasis
- Oxidative stress
- Global under-methylation, synthesis and repair of DNA
- Immune dysregulation/autoimmunity
- Cardiovascular disease
- Congenital heart disease and birth defects
- Impaired endogenous detoxification processes
- Increased risk for Down's syndrome
Methionine is first enzymatically converted to S-adnosylmethionine (SAM), the principal methyl donor for methylation of DNA, RNA, protein, phospholipids, creatinine and neurotransmitters. S-adenosylhomocysteine (SAH) is generated as a product of all SAM-dependent methylation reactions and is hydrolyzed to homocysteine (Hcy) and adenosine through a reversible reaction (AHCY). SAH is a potent inhibitor of all SAM-dependent methylation reactions. Efficient removal of adenosine and Hcy is imperative to prevent accumulation of SAH. The enzymatic activities of adenosine kinase, adenosine deaminase and 5'-nucleosidases contribute to maintaining normal levels of adenosine.
Hcy is normally primarily removed or recycled by remethylation to methionine through a series of reactions that require 5-methyltetrahydrofolate, B12
and betaine to complete the normal methionine cycle. A low ratio of SAM to SAH is a sensitive indicator of under-methylation. elevated plasma Hcy is an independent risk factor for cardiovascular disease (CVD). Recent research suggests that elevated SAH may be an even better predictor of risk for CVD.
Methionine > Homocysteine > Cysteine The methionine transsulfuration pathway occurs primarily in the liver and kidneys, and diverts Hcy away from remethylation to methionine toward synthesis of conditionally essential amino acid cysteine, essential sulfate, taurine and glutathione. Homocysteine in the presence of serine and B6
is enzymatically converted to cystathionine and ultimately cysteine. Cysteine is the rate-limiting amino acid in the biosynthesis of quintessential glutathione (GSH). GSH is pivotal in the regulation of intracellular redox homeostasis, oxidative stress, immune function, DNA synthesis and repair. apoptosis and detoxification of metals and chemicals. The DDI Methylation Profile evaluates the plasma levels of methionine, cysteine, SAM, SAH, Hcy, adenosine and cystathionine, and provides the important "methylation index," a ration of SAM to SAH. The test results can facilitate appropriate individualized interventions to improve or normalize methionine metabolism and ameliorate or prevent adverse consequences associated with inadequate methylation and/or transsulfuration capacity.