Gamma-glutamyl carboxylase
Encyclopedia
Gamma-glutamyl carboxylase is an enzyme
that in humans is encoded by the GGCX gene
, located on chromosome 2 at 2p12.
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. Most gla domain
-containing proteins depend on this carboxylation reaction for posttranslational modification
. In humans, the gamma-glutamyl carboxylase enzyme is most highly expressed in the liver.
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.
-like disorder with multiple coagulation factor deficiency.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that in humans is encoded by the GGCX gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
, located on chromosome 2 at 2p12.
Function
Gamma-glutamyl carboxylase is an enzyme that catalyzes the posttranslational modificationPosttranslational modification
Posttranslational modification is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis, and thus gene expression, for many proteins....
of vitamin K
Vitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
-dependent proteins. Many of these vitamin K-dependent proteins are involved in coagulation
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
so the function of the encoded enzyme is essential for hemostasis. Most gla domain
Gla domain
Vitamin K-dependent carboxylation/gamma-carboxyglutamic domain is a protein domain that contains post-translational modifications ofmany glutamate residues by vitamin K-dependent carboxylation to form gamma-carboxyglutamate . The Gla residues are responsible for the high-affinity binding of...
-containing proteins depend on this carboxylation reaction for posttranslational modification
Posttranslational modification
Posttranslational modification is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis, and thus gene expression, for many proteins....
. In humans, the gamma-glutamyl carboxylase enzyme is most highly expressed in the liver.
Catalytic reaction
Gamma-glutamyl carboxylase oxidizes Vitamin KVitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
hydroquinone to Vitamin K 2,3 epoxide, while simultaneously adding CO2 to protein-bound glutamic acid
Glutamic acid
Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...
(abbreviation = Glu) to form gamma-carboxyglutamic acid (also called gamma-carboxyglutamate
Carboxyglutamate
Carboxyglutamic acid , is an uncommon amino acid introduced into proteins by a post-translational carboxylation of glutamic acid residues. This modification is found, for example, in clotting factors and other proteins of the coagulation cascade. This modification introduces an affinity for calcium...
, 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.
Clinical significance
Mutations in this gene are associated with vitamin K-dependent coagulation defect and PXEPseudoxanthoma elasticum
Pseudoxanthoma elasticum , also known as Grönblad–Strandberg syndrome, is a genetic disease that causes fragmentation and mineralization of elastic fibers in some tissues. The most common problems arise in the skin and eyes, and later in blood vessels in the form of premature atherosclerosis...
-like disorder with multiple coagulation factor deficiency.