Cysteine metabolism explained

Cysteine metabolism refers to the biological pathways that consume or create cysteine. The pathways of different amino acids and other metabolites interweave and overlap to creating complex systems.

Human cysteine metabolism

In human cysteine metabolism, L-cysteine is consumed in several ways as shown below. L-Cysteine is also consumed in pantothenate/coenzyme A biosynthesis.

L-Cysteine consumption pathways

Enzyme	→	Products	Cofactor/Additional Reactant
cysteine dioxygenase^[1]	→	cysteine sulfinic acid	iron
serine racemase^[2]	→	D-cysteine	pyridoxal phosphate
cysteine lyase^[3]	→	L-cysteate/hydrogen sulfide	pyridoxal phosphate/sulfite
cystathionine γ-lyase^[4]	→	pyruvate/NH3/H2S	pyridoxal phosphate
cysteine—tRNA ligase^[5]	→	L-cysteinyl-tRNA^Cys
cystine reductase^[6]	→	L-cystine/NADH and H+	NAD+
cysteine transaminase^[7]	→	3-mercapto-pyruvate/L-glutamate	pyridoxal phosphate/alpha-ketoglutaric acid
glutamate–cysteine ligase^[8]	→	γ-glutamyl cysteine/ADP and Pi	ATP

L-Cysteine is the product of several processes as well. In addition to the reactions below, L-cysteine is also a product of glycine, serine, and threonine metabolism.

L-cysteine production pathways

Reactants	→	Enzyme	Cofactors	Notes
O-acetyl-L-serine/hydrogen sulfide	→	cysteine synthase^[9]	pyridoxal phosphate	not present in humans
L-cystine/2 glutathione	→	glutathione-cystine transhydrogenase^[10]
cystathionine	→	cystathionine γ-lyase	pyridoxal phosphate
3-mercapto-pyruvate	→	cysteine transaminase	pyridoxal phosphate

See also

• D-cysteine desulfhydrase
• Sulfur metabolism

Notes and References

1. Stipanuk MH, Ueki I, Dominy JE, Simmons CR, Hirschberger LL . Cysteine dioxygenase: a robust system for regulation of cellular cysteine levels . Amino Acids . 37 . 1 . 55–63 . May 2009 . 19011731 . 2736881 . 10.1007/s00726-008-0202-y .
2. Roychaudhuri R . Mammalian D-Cysteine: A new addition to the growing family of biologically relevant D-amino acids . Chirality . chir.23555 . March 2023 . 36890664 . 10.1002/chir.23555 . 257426578 .
3. Tolosa EA, Chepurnova NK, Khomutov RM, Severin ES . Reactions catalysed by cysteine lyase from the yolk sac of chicken embryo . Biochimica et Biophysica Acta (BBA) - Enzymology . 171 . 2 . 369–371 . February 1969 . 5813025 . 10.1016/0005-2744(69)90174-0 . free .
4. Sun Q, Collins R, Huang S, Holmberg-Schiavone L, Anand GS, Tan CH, van-den-Berg S, Deng LW, Moore PK, Karlberg T, Sivaraman J . 6 . Structural basis for the inhibition mechanism of human cystathionine gamma-lyase, an enzyme responsible for the production of H(2)S . English . The Journal of Biological Chemistry . 284 . 5 . 3076–3085 . January 2009 . 19019829 . 10.1074/jbc.M805459200 . free .
5. Mccorquodale DJ . The separation and partial purification of aminoacyl-RNA synthetases from Escherichia coli . Biochimica et Biophysica Acta (BBA) - Specialized Section on Nucleic Acids and Related Subjects . 91 . 4 . 541–548 . December 1964 . 14262440 . 10.1016/0926-6550(64)90001-5 .
6. Maresca B, Jacobson E, Medoff G, Kobayashi G . Cystine reductase in the dimorphic fungus Histoplasma capsulatum . Journal of Bacteriology . 135 . 3 . 987–992 . September 1978 . 211119 . 222474 . 10.1128/jb.135.3.987-992.1978 .
7. Hipólito A, Nunes SC, Vicente JB, Serpa J . Cysteine Aminotransferase (CAT): A Pivotal Sponsor in Metabolic Remodeling and an Ally of 3-Mercaptopyruvate Sulfurtransferase (MST) in Cancer . Molecules . 25 . 17 . 3984 . September 2020 . 32882966 . 7504796 . 10.3390/molecules25173984 . free .
8. Chen Y, Shertzer HG, Schneider SN, Nebert DW, Dalton TP . Glutamate cysteine ligase catalysis: dependence on ATP and modifier subunit for regulation of tissue glutathione levels . English . The Journal of Biological Chemistry . 280 . 40 . 33766–33774 . October 2005 . 16081425 . 10.1074/jbc.M504604200 . free .
9. Kredich NM, Becker MA, Tomkins GM . Purification and characterization of cysteine synthetase, a bifunctional protein complex, from Salmonella typhimurium . The Journal of Biological Chemistry . 244 . 9 . 2428–2439 . May 1969 . 10.1016/S0021-9258(19)78241-6 . 4977445 . free .
10. Nagai S, Black S . A thiol-disulfide transhydrogenase from yeast . The Journal of Biological Chemistry . 243 . 8 . 1942–1947 . April 1968 . 10.1016/S0021-9258(18)93532-5 . 5646485 . free .