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Research Methionine (Plasma)
OMX Organic Metabolomics / Diagnostic Solutions Diagnostic Solutions Laboratory

Methionine (Plasma)

Optimal Result: 12.1 - 38.5 nmol/ML.

Methionine is a sulfur-containing amino acid that functions as a methyl donor in the methylation process. It is also involved in glutathione production, an endogenous antioxidant that can neutralize reactive oxygen species. Depletion of glutathione can lead to mitochondrial dysfunction. Glutathione is made up of three amino acids, glycine, cysteine (cystine), and glutamic acid.

Methionine is obtained from dietary intake or through homocysteine remethylation. Methionine’s dietary sources include eggs, fish, meats, Brazil nuts, and other plant seeds. Methionine is converted to the body’s main methyl donor, S-adenosylmethionine (SAM). This conversion requires the enzyme methionine adenosyltransferase (MAT).

- Higher in those on a high protein diet; higher in fish eaters, along with tryptophan and tyrosine.

- Higher plasma methionine levels have been noted in liver disease.

- Elevated plasma methionine has been proposed to distinguish patients with homocystinuria due to in-born errors from those with B-vitamin deficiencies or renal failure, which would have normal or lower methionine levels.

- A cystathionine-beta-synthase deficiency can lead to an increase in blood methionine and cystathionine.

- Urine methionine significantly increased in hepatocellular carcinoma patients.

- Blood methionine was found lower in those with depression, multiple sclerosis.

- Lower levels have been noted in those on a low protein diet, or significantly reduced calorie intake.

References:

- Adrych K, Smoczynski M, Stojek M, et al. Decreased serum essential and aromatic amino acids in patients with chronic pancreatitis. World J Gastroenterol. 2010;16(35):4422-4427.

- Kawaguchi Y, Ogawa M, Ito H, Mine T. Alterations in plasma amino acid levels in alcoholic chronic pancreatitis in Japanese. Digestion. 2012;86(2):155-160.

- Schmidt JA, Rinaldi S, Scalbert A, et al. Plasma concentrations and intakes of amino acids in male meat-eaters, fish-eaters, vegetarians and vegans: a cross-sectional analysis in the EPIC-Oxford cohort. Eur J Clin Nutr. 2016;70(3):306-312.

- Mudd SH. Hypermethioninemias of genetic and non-genetic origin: A review. Am J Med Gen Part C. 2011;157c(1):3-32.

- Baric I, Staufner C, Augoustides-Savvopoulou P, et al. Consensus recommendations for the diagnosis, treatment and follow-up of inherited methylation disorders. J Inherit Metab Dis. 2017;40(1):5-20.

- Velayutham M, Hemann CF, Cardounel AJ, Zweier JL. Sulfite Oxidase Activity of Cytochrome c: Role of Hydrogen Peroxide. Biochem Biophys Rep. 2016;5:96-104.

- Chien Y-H, Abdenur JE, Baronio F, et al. Mudd’s disease (MAT I/III deficiency): a survey of data for MAT1A homozygotes and compound heterozygotes. Orphanet J Rare Dis. 2015;10(1):99.

- Bertolo RF, McBreairty LE. The nutritional burden of methylation reactions. Curr Op Clinl Nutr Metab Care. 2013;16(1):102-108.

- Ho V, Massey TE, King WD. Effects of methionine synthase and methylenetetrahydrofolate reductase gene polymorphisms on markers of one-carbon metabolism. Genes Nutr. 2013;8(6):571-580.

- Vannucchi H, Moreno FS, Amarante AR, de Oliveira JE, Marchini JS. Plasma amino acid patterns in alcoholic pellagra patients. Alcohol Alcoholism. 1991;26(4):431-436.

What does it mean if your Methionine (Plasma) result is too high?

- Higher in those on a high protein diet; higher in fish eaters, along with tryptophan and tyrosine.

- Higher plasma methionine levels have been noted in liver disease.

- Elevated plasma methionine has been proposed to distinguish patients with homocystinuria due to in-born errors from those with B-vitamin deficiencies or renal failure, which would have normal or lower methionine levels.

- A cystathionine-beta-synthase deficiency can lead to an increase in blood methionine and cystathionine.

- Urine methionine significantly increased in hepatocellular carcinoma patients.

Methionine elevations are most commonly caused by increased dietary intake.

However, increases can also be due to abnormalities within the methylation cycle itself producing a passive methionine elevation.

Genetic SNPs for several methylation and transsulfuration enzymes, or the lack of necessary vitamin and mineral cofactors, can alter methionine’s metabolism. For example, a nutritional cofactor deficiency (magnesium/potassium), ATP depletion, or a SNP in the MAT enzyme, can downregulate the conversion to SAM and may lead to elevated methionine. Vitamin B6 deficiency, a cofactor for the downstream enzyme responsible for homocysteine transsulfuration, can result in excess homocysteine re-methylation back to methionine, thus increasing methionine. Additionally, molybdenum is a cofactor in methionine degradation and catabolism, therefore molybdenum insufficiency can contribute to high levels of methionine.

Mild elevations in methionine do not cause serious adverse clinical effects. There is literature regarding CNS abnormalities seen with excessive elevations, but this is rare and more commonly seen with inborn errors of metabolism (MATI/III deficiency also known as Mudd’s disease).

What does it mean if your Methionine (Plasma) result is too low?

- Blood methionine was found lower in those with depression, multiple sclerosis.

- Lower levels have been noted in those on a low protein diet, or significantly reduced calorie intake.

Low levels of essential amino acids may indicate a poor-quality diet, or maldigestion due to deficient digestive peptidase activity or pancreatic dysfunction. A dietary methionine deficiency (low intake or malabsorption/maldigestion) can affect the methylation cycle, given its critical role. Increasing methionine dietary sources, methionine supplementation, or methylated product supplementation can mitigate the adverse impact. Because vitamins B12 and folate are needed to remethylate homocysteine into methionine, functional need for these cofactors may contribute to low methionine levels. Lastly, vitamin B3 deficiency has been associated with low levels of several amino acids.

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