Methylation Panel - Genova Diagnostics
Methylation is a biochemical process in which methyl groups (CH3) are transferred or donated between molecules, thereby changing their structure and function. This happens billions of times per second in every cell throughout the body. The methylation cycle is dependent on amino acids, vitamin cofactors, and minerals obtained from the diet to ensure adequate function of this biochemical pathway.
The incredibly vast processes in the body that depend upon methylation are what ultimately make functional testing for methylation impairment a valuable clinical tool. Some of these processes include, but are not limited to:
- creatine production for skeletal muscle contraction
- DNA and RNA synthesis
- gene regulation (epigenetics)
- hormone regulation and detoxification
- energy production
- cell membrane repair
- fat metabolism
- immune function
- neurotransmitter production and metabolism
- vascular endothelial function and nitric oxide production
To keep these processes functioning optimally, there is a necessary balance between many different biochemical pathways. What is termed the “methylation cycle” involves an interplay between folate metabolism, methionine metabolism, and homocysteine transsulfuration.
The body continually adapts these interconnected pathways in order to maintain homeostasis.
However, key amino acid deficiencies, a lack of vitamin and mineral cofactors, genetic enzymatic predispositions, and a wide array
of oxidative stressors can impact multiple enzymes leading to a disruption in a patient’s overall methylation status.
BetaineOptimal range: 21 - 71 micromol/L
- Betaine (trimethylglycine) can be used to turn homocysteine back into methionine
- Betaine is derived from dietary choline (Meats, eggs, and beets)
- Betaine is used for: Methylation / Osmolyte, under cell stress (mainly in kidneys)LEARN MORE
Betaine/Choline RatioOptimal range: 2.6 - 7.7 Ratio
Betaine and choline can be obtained from the diet or synthesized de novo.
Betaine is derived from dietary choline – nuts, cauliflower and broccoli, beets, meats, and eggs.
Choline is a lipotrope, in that it helps to mobilize fat from the liver. Phosphatidylcholine, a derivative, is required for the production of hepatic very-low-density lipoprotein and the mobilization of fat from the liver. Therefore, choline deficiency can result in fatty liver and liver abnormalities.LEARN MORE
CholineOptimal range: 5.2 - 13 micromol/L
Choline is a nutrient that supports various bodily functions, including cellular growth and metabolism. The body makes some choline, but the majority comes from dietary sources.LEARN MORE
Cyst(e)ineOptimal range: 271 - 392 micromol/L
CystathionineOptimal range: 74 - 369 nanomol/L
Because cystathionine is an intermediate of the transsulfuration pathway, elevation of this biomarker may indicate a backup of the transsulfuration pathway. Conversion of cystathionine to glutathione requires necessary cofactors, such as vitamin B6, zinc, glycine, and magnesium. Therefore, transient elevations of this metabolite may indicate increased need for these cofactors.LEARN MORE
Dimethylglycine (DMG)Optimal range: 1.6 - 5 micromol/L
The amino acid derivative dimethylglycine (DMG) is produced when betaine (trimethylglycine) donates a methyl group to homocysteine for re-methylation back to methionine. This methyl donation is mediated by the enzyme betaine homocysteine methyltransferase (BHMT). Elevations in DMG act as a negative feedback by inhibiting this enzymatic conversion. [L]LEARN MORE
GlutathioneOptimal range: 669 - 5000 micromol/L
Glutathione (GSH) is a tripeptide comprised of three amino acids (cysteine, glycine, and glutamic acid). Glutathione is the body’s most potent intracellular antioxidant. It exists intracellularly in either an oxidized or reduced state.
GSH acts as an antioxidant, free radical scavenger, and detoxifying agent. Excessive formation of reactive oxygen species (ROS), including hydrogen peroxide (H2O2), is toxic to the cell. Hence, the metabolism of these free radicals are critical, and they are tightly controlled. [L]LEARN MORE
GlycineOptimal range: 181 - 440 micromol/L
Glycine is a nonessential amino acid with many important physiologic functions. It is one of three amino acids that make up glutathione. Glycine’s dietary sources include meat, fish, legumes, and gelatins.
Glycine is a major collagen and elastin component, which are the most abundant proteins in the body. Like taurine, it is an amino acid necessary for bile acid conjugation; therefore, it plays a key role in lipid digestion and absorption. [L] Glycine is the precursor to various important metabolites such as porphyrins, purines, heme, and creatine. It acts both as an inhibitory neurotransmitter in the CNS (via its interaction with strychnine-sensitive glycine receptors), and as an excitatory neurotransmitter on N-methyl-D-aspartate (NMDA) receptors. [L]LEARN MORE
HomocysteineOptimal range: 3.7 - 10.4 micromol/L
- Homocysteine is often used as an indicator of methylation status
- Clinicians aim for optimal: 2-10μmol/L
- Homocysteine must be recycled back into methionineLEARN MORE
Met/Sulf Balance RatioOptimal range: 0.55 - 0.64 Ratio
This calculated ratio is called the ‘Met/Sulf Balance’ and it compares analytes between the methylation pathway and transsulfuration pathways.
Biomarker levels are compared proportionately allowing potential insight into which of the pathways is being favored.
The four analytes from the main methylation pathway that are used in the Met/Sulf Balance are SAM, SAH, methionine, and homocysteine. The four analytes from the transsulfuration pathway are cystathionine, cysteine, taurine, and glutathione.LEARN MORE
MethionineOptimal range: 23 - 38 micromol/L
Methionine is an essential amino acid that plays an important role in the methylation cycle.LEARN MORE
Methylation Balance RatioOptimal range: 1.03 - 1.2 Ratio
Compares 8 different biomarkers
– 4 biomarkers with a methyl group to give
– 4 biomarkers that have had a methyl group removed
The clinical utility of the Methylation Balance Ratio is that it represents a potential way to detect subtle methylation imbalance prior to alterations in the SAM/SAH ratio.
Methylated Metabolites are:
Un-Methylated Metabolites are:
S-adenosylhomocysteine (SAH)Optimal range: 16 - 41 nanomol/L
S-adenosylhomocysteine (SAH) is the end-product of methylation reactions in the body. SAM ultimately donates a methyl group for methylation (DNA, detoxification, etc.) resulting in SAH formation. SAH is also the metabolic precursor of all the homocysteine (Hcy) produced in the body. In literature, SAH is sometimes referred to as AdoHcy.LEARN MORE
S-adenosylmethionine (SAM)Optimal range: 65 - 150 nanomol/L
- The methylation cycle is all about making sure there is adequate SAM (S-adenosylmethionine)
- SAM is overwhelmingly the body’s main methyl donor
- Think of SAM as the body’s methylation currency
- SAM can donate a methyl group wherever it is neededLEARN MORE
SerineOptimal range: 91 - 161 micromol/L
Serine is a nonessential amino acid used in protein biosynthesis. In the folate cycle, glycine and serine are interconverted by the enzyme serine hydroxymethyltransferase (SHMT). Glycine accepts a methyl donor from 5-10 MTHF and becomes serine; therefore, serine is methylated glycine. [L] These methyltransferase reactions and interconversions are readily reversible depending on the needs of the folate cycle. [L]LEARN MORE
TaurineOptimal range: 50 - 139 micromol/L
Taurine differs from other amino acids because a sulfur group replaces the carboxyl group of what would be the non-essential amino acid, β-alanine. It takes part in biochemical reactions and is not fully incorporated into proteins. In most tissues, it remains a free amino acid. Taurine’s highest concentration is in muscle, platelets, and the central nervous system. Taurine is mainly obtained via dietary sources (dairy, shellfish, turkey, energy drinks), but can also come from sulfur amino acid metabolism (methionine and cysteine). [L], [L]LEARN MORE