Vitamin K‐dependent Carboxylase

Abstract

Proteins are posttranslationally modified by specific γ‐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; γ‐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 γ‐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 γ‐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.

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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]