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Research Cystathionine
Amino Acids test [Great Plains Laboratory / Doctor's Data] Doctor's Data

Cystathionine

Optimal Result: 7 - 40 qM/g creatinine.

Cystathionine is an intermediate dipeptide within the process of transsulfuration. Transsulfuration is the main route for irreversible homocysteine disposal, glutathione production, and energy. The initial step involves the enzyme cystathionine β-synthase enzyme (CBS). This reaction requires nutrient cofactors such as vitamin B6 and iron. Cystathionine is then converted to cysteine, and eventually goes on to either make glutathione or feed the Kreb’s cycle. Currently, there is no known source or physiologic function for cystathionine other than serving as a transsulfuration intermediate. Some literature suggests that cystathionine may exert protection against endoplasmic reticulum stress-induced tissue damage and cell death, but studies are sparse.

References:

- Maclean KN, Greiner LS, Evans JR, et al. Cystathionine protects against endoplasmic reticulum stress-induced lipid accumulation, tissue injury, and apoptotic cell death. J Biol Chem. 2012;287(38):31994-32005.

- Lamers Y, Williamson J, Ralat M, et al. Moderate dietary vitamin B-6 restriction raises plasma glycine and cystathionine concentrations while minimally affecting the rates of glycine turnover and glycine cleavage in healthy men and women. J Nutr. 2009;139(3):452-460.

- Obeid R. The metabolic burden of methyl donor deficiency with focus on the betaine homocysteine methyltransferase pathway. Nutrients. 2013;5(9):3481-3495.

- Stabler SP, Lindenbaum J, Savage DG, Allen RH. Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency. Blood. 1993;81(12):3404-3413.

- Blom HJ, Smulders Y. Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects. J Inherit Metab Dis. 2011;34(1):75-81.

- Wu XY, Lu L. Vitamin B6 deficiency, genome instability and cancer. Asian Pac J Cancer Prev. 2012;13(11):5333-5338.

What does it mean if your Cystathionine result is too high?

Because cystathionine is an intermediate of the transsulfuration pathway, elevation of this biomarker may indicate a downstream backup of the transsulfuration pathway. Conversion of cystathionine to glutathione, or other transsulfuration metabolites, requires necessary cofactors, such as vitamin B6, zinc, glycine, and magnesium. Therefore, transient elevations of this metabolite may indicate increased need for these cofactors.

Elevated cystathionine may be seen in individuals who have a CBS SNP which upregulates this enzyme and therefore upregulates the conversion of homocysteine to cystathionine.

Elevated S-adenosylmethionine (SAM) directly upregulates the CBS enzyme leading to higher cystathionine levels.

Dimethylglycine (DMG) or trimethylglycine (betaine) supplementation contribute to maintaining methylation. If the methylation cycle is adequate, transsulfuration is then upregulated. With this, supplementation of DMG or betaine have been associated with elevated cystathionine.

Elevated homocysteine may increase its metabolism into transsulfuration. Therefore, in vitamin B12 and folate deficiencies which result in high homocysteine, cystathionine might also be elevated.

What does it mean if your Cystathionine result is too low?

Abnormalities within the methylation cycle can result in lower levels of cystathionine. Low levels of SAM, or methylation imbalances, result in the body preferentially deferring transsulfuration to maintain methylation. Because the CBS enzyme requires vitamin B6 as a cofactor, deficiencies in vitamin B6 may result in lower cystathionine.

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