Carboxyglutamic acid

Carboxyglutamic acid (or γ-carboxyglutamic acid, abbreviated as Gla) is a non-standard amino acid that plays a pivotal role in the body's blood coagulation process. It is characterized by the presence of a γ-carboxyl group on the glutamic acid. Unlike the common amino acids that make up proteins, Gla is formed by the modification of glutamic acid residues in certain proteins, a process that is vitamin K-dependent. This modification allows these proteins to bind calcium ions, which is essential for their biological activity.

Structure and Function

Carboxyglutamic acid contains an extra carboxyl group attached to the gamma carbon of glutamic acid. This modification significantly alters the chemical properties of the amino acid, enabling it to chelate (bind) calcium ions. The ability to bind calcium ions is crucial for the function of Gla-containing proteins, often referred to as Gla proteins. These proteins are involved in various physiological processes, including blood coagulation, bone metabolism, and the regulation of vascular calcification.

Biosynthesis

The biosynthesis of carboxyglutamic acid is a post-translational modification that occurs in the liver. This process requires vitamin K as a cofactor. In the presence of vitamin K, specific glutamic acid residues in the target proteins are carboxylated to form Gla. This reaction is catalyzed by the enzyme γ-glutamyl carboxylase. The importance of vitamin K in this process underlines the vitamin's role in blood coagulation and bone health.

Role in Blood Coagulation

In the context of blood coagulation, Gla residues are critical for the function of several clotting factors, including prothrombin (Factor II), Factor VII, Factor IX, and Factor X. These Gla-containing clotting factors can bind to phospholipid surfaces in the presence of calcium ions, positioning them optimally for the coagulation cascade. This interaction is essential for the sequential activation of clotting factors that leads to the formation of a blood clot.

Role in Bone Metabolism

Carboxyglutamic acid is also found in proteins involved in bone metabolism, such as Osteocalcin, which is the most abundant non-collagen protein in bone. Osteocalcin binds calcium and is believed to play a role in regulating bone mineralization and calcium ion homeostasis.

Clinical Significance

Deficiencies in vitamin K, or defects in the carboxylation process, can lead to impaired blood clotting and increased risk of bleeding. Additionally, abnormalities in Gla proteins have been implicated in vascular calcification and osteoporosis, highlighting the importance of carboxyglutamic acid in cardiovascular and bone health.

See Also

• Vitamin K
• Blood coagulation
• Osteocalcin
• Amino acid metabolism