Cysteine is a nonessential sulfur-containing amino acid. It is obtained from the diet and is also endogenously made from the intermediate amino acid cystathionine. Dietary cysteine sources include poultry, eggs, beef, and whole grains.
This amino acid should not be confused with the oxidized derivative of cysteine called cystine. Cystine is formed by combining two cysteine molecules within a redox reaction. The urinary FMV amino acid test reports cysteine and cystine separately. The plasma amino acid test combines both cysteine and cystine as one biomarker -cyst(e)ine.
Cysteine is an important component of glutathione. Recent studies provide some data to support the view that cysteine may be a limiting amino acid for glutathione synthesis in humans. This synthesis requires the enzyme glutathione synthetase (GSS). Cysteine can alternatively be converted to taurine (another amino acid) and the organic acid pyruvate, which are used in the mitochondrial citric acid cycle and/or excreted in the urine. When cysteine levels are low, this favors their utilization in glutathione formation during oxidative stress, given the importance of glutathione. Conversely, high levels of cysteine in the absence of oxidative stress favor its metabolism towards pyruvate and taurine.
References:
- 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.
- Wu XY, Lu L. Vitamin B6 deficiency, genome instability and cancer. Asian Pac J Cancer Prev. 2012;13(11):5333-5338.
- Larsson SC, Hakansson N, Wolk A. Dietary cysteine and other amino acids and stroke incidence in women. Stroke. 2015;46(4):922-926.
- Lyons J, Rauh-Pfeiffer A, Yu Y, et al. Blood glutathione synthesis rates in healthy adults receiving a sulfur amino acid-free diet. Proc Nat Acad Sci. 2000;97(10):5071-5076.
- Stipanuk MH, Ueki I. Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur. J Inherit Metab Dis. 2011;34(1):17-32.
- Stipanuk MH, Coloso RM, Garcia RAG, Banks MF. Cysteine Concentration Regulates Cysteine Metabolism to Glutathione, Sulfate and Taurine in Rat Hepatocytes. J Nutr. 1992;122(3):420-427.
- Bender D, Kaczmarek AT, Santamaria-Araujo JA, et al. Impaired mitochondrial maturation of sulfite oxidase in a patient with severe sulfite oxidase deficiency. Human Mol Gen. 2019;28(17):2885-2899.
- DeStefano Vea. Linkage disequilibrium at the cystathionine beta-synthase (CBS) locus and the association between genetic variation at the CBS locus and plasma levels of homocysteine. Ann Human Gen. 1998;62(6):481-490.
- Carmel R, Melnyk S, James SJ. Cobalamin deficiency with and without neurologic abnormalities: differences in homocysteine and methionine metabolism. Blood. 2003;101(8):3302-3308.
- Brito A, Grapov D, Fahrmann J, et al. The Human Serum Metabolome of Vitamin B-12 Deficiency and Repletion, and Associations with Neurological Function in Elderly Adults. J Nutr. 2017;147(10):1839-1849.
- 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.
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A diet high in cysteine-rich proteins can elevate cysteine levels. As with all sulfur-containing amino acids, the enzyme sulfite oxidase catabolizes the amino acid into sulfite for excretion.
An important cofactor for this enzyme is molybdenum. With that, insufficient molybdenum can contribute to elevated cysteine.
Homocysteine is pulled into the transsulfuration pathway via the enzyme cystathionine-beta-synthase (CBS) to become cysteine, with cystathionine formation as an intermediate step. Cysteine levels may be elevated due to a CBS SNP which results in an upregulation of the enzyme and more cystathionine and cysteine production.
Zinc is an important cofactor downstream from cysteine in transsulfuration. Because of this, cysteine elevations can also be seen in zinc insufficiency.
Vitamin B12 may also be a cofactor in the peripheral utilization of cysteine; therefore functional deficiencies of vitamin B12 can contribute to higher levels.
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Low dietary protein intake, GI malabsorption, and maldigestion may all contribute to lower amino acid levels.
Because vitamin B6 is a cofactor in several steps within the transsulfuration pathways, deficiency may contribute to lower cysteine by inhibiting or slowing the enzyme that converts cystathionine to cysteine.
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