Vitamin K-dependent Carboxylase

John W Suttie, University of Wisconsin‐Madison, Madison, Wisconsin, USA

Published online: April 2001

DOI: 10.1038/npg.els.0000864

Proteins are posttranslationally modified by specific -glutamyl carboxylation. It is believed this reaction is the only known metabolic role of the vitamin K-dependent enzyme that carries out this carboxylation.

Keywords: phylloquinone; menaquinones; vitamin K; -carboxyglutamic acid; warfarin

Figure 1. Structures of (a) phylloquinone and (b) an example of a bacterially produced long-chain menaquinone, menaquinone-8.
Figure 2. Current understanding of the bioorganic mechanism utilized to -carboxylate a glutamyl residue and oxidize the hydronaphthoquinone form of vitamin K to its 2,3-epoxide.
Figure 3. Cellular metabolism of vitamin K mediated by the vitamin K-dependent carboxylase and the vitamin K epoxide reductase. Inhibition of this cycle by warfarin at both steps of the reductase and the carboxylase by specific inhibitors is indicated.
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 References
    Berkner KL and Pudota BN (1998) Vitamin K-dependent carboxylation of the carboxylase. Proceedings of the National Academy of Sciences of the USA 95: 466–471.
    Cain D, Hutson SM and Wallin R (1997) Assembly of the warfarin-sensitive vitamin K 2,3-epoxide reductase enzyme complex in the endoplasmic reticulum membrane. Journal of Biological Chemistry 272: 29068–29075.
    Dowd P, Hershline R, Ham SW and Naganathan S (1995) Vitamin K and energy transduction: a base strength amplification mechanism. Science 269: 1684–1691.
    Esmon CT, Sadowski JA and Suttie JW (1975) A new carboxylation reaction. The vitamin K-dependent incorporation of  H14CO3– into prothrombin. Journal of Biological Chemistry 250: 4744–4748.
    Fasco MJ, Hildebrandt EF and Suttie JW (1982) Evidence that warfarin anticoagulant action involves two distinct reductase activities. Journal of Biological Chemistry 257: 11210–11212.
    Roth DA, Whirl ML, Velazquez-Estades LJ et al. (1995) Mutagenesis of vitamin K-dependent carboxylase demonstrates a carboxyl terminus-mediated interaction with vitamin K hydroquinone. Journal of Biological Chemistry 270: 5305–5311.
    Wu S-M, Morris DP and Stafford DW (1991a) Identification and purification to near homogeneity of the vitamin K-dependent carboxylase. Proceedings of the National Academy of Sciences of the USA 88: 2236–2240.
    Wu S-M, Cheung W-F, Frazier D and Stafford D (1991b) Cloning and expression of the cDNA for human -glutamyl carboxylase. Science 254: 1634–1636.
 Further Reading
    Berkner KL (2000) The vitamin K-dependent carboxylase. Journal of Nutrition 130: 1877–1880.
    Furie B, Bouchard BA and Furie BC (1999) Vitamin K-dependent biosynthesis of -carboxyglutamic acid. Blood 93: 1798–1808.
    Suttie JW (1993) Synthesis of vitamin K-dependent proteins. FASEB Journal 7: 445–452.

Related Sub-Topics:

Posttranslational Modification | Proteins: Structure, Function, Metabolism | Other Biomolecules: Structure, Function, Metabolism | Enzymes: Structure and Action Mechanism
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Article Title: Vitamin K-dependent Carboxylase
 
How to Cite close
Suttie, John W(Apr 2001) Vitamin K-dependent Carboxylase. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0000864]