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Gamma-glutamyl carboxylase
Introduction
Gamma-glutamyl carboxylase is an enzyme that in humans is encoded by the GGCX gene, located on chromosome 2 at 2p12.[1]
Function
Function
Gamma-glutamyl carboxylase is an enzyme that catalyzes the posttranslational modification of vitamin K-dependent proteins. Many of these vitamin K-dependent proteins are involved in coagulation so the function of the encoded enzyme is essential for hemostasis.[2] Most gla domain-containing proteins depend on this carboxylation reaction for posttranslational modification.[3] In humans, the gamma-glutamyl carboxylase enzyme is most highly expressed in the liver.
Catalytic reaction
Catalytic reaction
Gamma-glutamyl carboxylase oxidizes Vitamin K hydroquinone to Vitamin K 2,3 epoxide, while simultaneously adding CO2 to protein-bound glutamic acid (abbreviation = Glu) to form gamma-carboxyglutamic acid (also called gamma-carboxyglutamate, abbreviation = Gla). The carboxylation reaction will only proceed if the carboxylase enzyme is able to oxidize vitamin K hydroquinone to vitamin K epoxide at the same time; the carboxylation and epoxidation reactions are said to be coupled reactions.[4][5][6]
2) + CO
2 + oxygen β a [protein] 4-carboxy-L-glutamate (Gla) + vitamin K 2,3-epoxide (KO) + H+
+ H
2O
Clinical significance
Clinical significance
Mutations in this gene are associated with vitamin K-dependent coagulation defect and PXE-like disorder with multiple coagulation factor deficiency.[2][7]
References
References
- β Wu SM, Cheung WF, Frazier D, Stafford DW (December 1991). “Cloning and expression of the cDNA for human gamma-glutamyl carboxylase”. Science. 254 (5038): 1634β6. doi:10.1126/science.1749935. PMIDΒ 1749935.
- β 2.0 2.1 “Entrez Gene: GGCX”.
- β Brenner B, Tavori S, Zivelin A, Keller CB, Suttie JW, Tatarsky I, Seligsohn U (August 1990). “Hereditary deficiency of all vitamin K-dependent procoagulants and anticoagulants”. Br. J. Haematol. 75 (4): 537β42. doi:10.1111/j.1365-2141.1990.tb07795.x. PMIDΒ 2145029.
- β Suttie JW (1985). “Vitamin K-dependent carboxylase”. Annu. Rev. Biochem. 54 (1): 459β77. doi:10.1146/annurev.bi.54.070185.002331. PMIDΒ 3896125.
- β Presnell SR, Stafford DW (2002). “The vitamin K-dependent carboxylase”. Thromb. Haemost. 87 (6): 937β46. PMIDΒ 12083499.
- β Silva PJ, Ramos MJ (2007). “Reaction mechanism of the vitamin K-dependent glutamate carboxylase: a computational study”. J Phys Chem B. 111 (44): 12883β7. doi:10.1021/jp0738208. PMIDΒ 17935315.
- β Vanakker OM, Martin L, Gheduzzi D, Leroy BP, Loeys BL, Guerci VI, Matthys D, Terry SF, Coucke PJ, Pasquali-Ronchetti I, De Paepe A (March 2007). “Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity”. J. Invest. Dermatol. 127 (3): 581β7. doi:10.1038/sj.jid.5700610. PMIDΒ 17110937.
Further reading
Further reading
- Bandyopadhyay PK (2008). “Vitamin K-dependent gamma-glutamylcarboxylation: an ancient posttranslational modification”. Vitam. Horm. 78: 157β84. doi:10.1016/S0083-6729(07)00008-8. PMIDΒ 18374194.
- Berkner KL (2008). “Vitamin K-dependent carboxylation”. Vitam. Horm. 78: 131β56. doi:10.1016/S0083-6729(07)00007-6. PMIDΒ 18374193.
- Oldenburg J, Marinova M, MΓΌller-Reible C, Watzka M (2008). “The vitamin K cycle”. Vitam. Horm. 78: 35β62. doi:10.1016/S0083-6729(07)00003-9. PMIDΒ 18374189.
- Berkner KL (2005). “The vitamin K-dependent carboxylase”. Annu. Rev. Nutr. 25 (1): 127β49. doi:10.1146/annurev.nutr.25.050304.092713. PMIDΒ 16011462.
- Zhang B, Ginsburg D (September 2004). “Familial multiple coagulation factor deficiencies: new biologic insight from rare genetic bleeding disorders”. J. Thromb. Haemost. 2 (9): 1564β72. doi:10.1111/j.1538-7836.2004.00857.x. PMIDΒ 15333032.
- Wallin R, Hutson SM (July 2004). “Warfarin and the vitamin K-dependent gamma-carboxylation system”. Trends Mol Med. 10 (7): 299β302. doi:10.1016/j.molmed.2004.05.003. PMIDΒ 15242675.
- Berkner KL (August 2000). “The vitamin K-dependent carboxylase”. J. Nutr. 130 (8): 1877β80. PMIDΒ 10917896.
- Presnell SR, Stafford DW (June 2002). “The vitamin K-dependent carboxylase”. Thromb. Haemost. 87 (6): 937β46. PMIDΒ 12083499.
- Bender, David A. (2003). Nutritional biochemistry of the vitamins. Cambridge, UK: Cambridge University Press. ISBNΒ 0-521-80388-8.
- Ball, George E. (2004). Vitamins: their role in the human body. Oxford: Blackwell Science. ISBNΒ 0-632-06478-1.
- Combs, Gerald F. (1998). The vitamins: fundamental aspects in nutrition and health. Boston: Academic Press. ISBNΒ 0-12-183492-1.
External links
External links
- glutamyl+carboxylase at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.