Amino acids are major nutrients that carry out several bodily functions. Asides from the twenty popular amino acids that are categorized as essential or nonessential there are some other amino acids that the body benefits from. A good example is the GLA amino acid which we will be examining in this article. GLA is the acronym for gamma-carboxyglutamic acid. GLA is found in a kidney protein, bone protein, a blood-clotting protein, and several ectopic calcification proteins. GLA is closely linked with blood clotting. Most proteins required for blood coagulation are made in the liver. Factor VIII is also synthesized with other tissues.
Six proteins take part in blood coagulation and they all need vitamin K to be synthesized completely: factor X, factor VII, prothrombin, factor IX, protein S, and protein C. The proteins are made in their precursor form. The liver cell has a region known as the rough endoplasmic reticulum where specific residues of glutamic acid are changed into modified glutamic acid called gamma-carboxyglutamic acid. This change is brought about by an enzymatic reaction called gamma-carboxylation and it needs the cofactor vitamin K.
What is Gla Amino Acid
Gamma carboxyglutamic acid also known as gla is a distinct amino acid that attaches to calcium. In protein, gamma carboxyglutamic acid combines to form sites of calcium-binding. Calcium stabilizes some vitamin K-dependent protein structural forms enabling the proteins to bind themselves to the cell membranes. Where vitamin K is absent or where there are antagonists of vitamin K like gamma-carboxylation, warfarin is inhibited. Proteins are then synthesized but they are gamma-carboxyglutamic acid deficient. The proteins lack biological activity as they cannot attach to calcium without interacting with membrane surfaces.
Another name for carboxyglutamic acid is carboxyglutamate which is as earlier stated an uncommon amino acid. It is introduced into proteins by residues of glutamic acid post-translational carboxylation. You can find this modification in coagulation cascade proteins and clotting factors. It is a modification that introduces an affinity to calcium ions. Blood coagulation cascade requires vitamin K to introduce clotting factors VII, VII, X, IX, and protein to gamma-carboxylation.
In gamma-carboxyglutamic acid biosynthesis, the gamma is abstracted from glutamic acid and CO2 is added subsequently. This reaction produces gamma-glutamyl carbanion. Carboxylase is the enzyme that catalyzes this reaction and uses vitamin K as a cofactor. We do not know how exactly vitamin K takes part In all this but a hypothesis exists explaining that a carboxylase free residue of cysteine converts it into a strong active base which becomes an abstract for hydrogen from the gamma carbon glutamic acid.
There are some residues of the gamma-carboxyglutamate present in the GLA acid-rich domain. This domain of GLA can be found in about a dozen proteins like coagulation factors VII, IX, XIV, and X, osteocalcin, transthyretin, prothrombin, vitamin-K dependent protein Z and S, inter-alpha inhibitor trypsin heavy chain, and GLA protein matrix. This GLA domain can be thanked for the high-affinity calcium ions that have, a necessary attribute for calcium-binding conformation and function.
Role of GLA in Coagulation
Residues of Gamma-carboxyglutamic acid play an important coagulation role. The calcium sites for binding have a high affinity in the domain for factor IX, a coagulation system serine protease was discovered to partially mediate factor IXa binding to platelets and activation of factor X.
In addition to this mechanical blood vessel injury which is a cell-associated factor becomes exposed leading to a cascade of some enzymatic reactions on membranes of accumulating platelets and cells. Residues of GLA partly govern the binding and activation of blood clotting circulating zymogens and enzymes to cell membranes that have been exposed.
To be specific, residues of GLA are important for exposing membranes that are hydrophobic and in calcium-binding. Insufficient or lack of these residues may cause anticoagulation or impaired coagulation which may result in thrombosis or bleeding diathesis. In addition to this, calcium ion removals from the proteins with organic chelators like citrate ions may lead to their dysfunction and stop blood coagulation. Citrate addition is a common method for storing blood in liquid form between when it is harvested and transfused.
The Place of Vitamin K
Vitamin K is not a popular vitamin but it is an essential one. It serves as a cofactor for enzymatic reaction – conversion of glutamic acid to gamma carboxyglutamic acid during its biosynthesis independent vitamin K proteins. Since vitamin K was discovered it has been linked to blood coagulation. A lot of effort has been put into understanding vitamin K’s biological roles.
An important breakthrough in the research field found antagonists of vitamin K and they were introduced as anticoagulation agents. Other highlights in the research included gamma-carboxy glutamic discovery in proteins that support blood clotting, identification of gamma carboxy glutamic amino acid to have the metal-binding ability, and confers it on proteins, enzymatic activity detection, the membrane of protein-membrane requirement. And catalyzes glutamic acid and CO2 incorporation.
Natural occurring vitamin K has a quinone oxidation state which has to be reduced to its hydroquinone form – an active vitamin K-dependent carboxylase cofactor. This carboxylase enzyme is responsible for the conversion into epoxide reductase vitamin K. the name was given because it reduces epoxide reductase vitamin K also.
Epoxide vitamin K reductase that works with low vitamin K quinone and epoxide concentration is most likely physiologically important in vitamin K recycling. Warfarin inhibits this enzyme and this results in insufficient amounts of hydroquinone vitamin K supporting full protein-dependent vitamin K carboxylation for blood coagulation. Therefore it is pharmacologically useful as an anticoagulant.
It is also believed that epoxide reductase of vitamin K enzymatic activity is found in multi-protein membrane-bound endoplasmic reticulum enzyme complexes.
Thus far we have learned the diverse aspects of gla amino acid and how it functions. The terms used in this article may be complex for you especially if you are not a science geek but In summary, we can say it is an essential amino acid that plays vital roles in blood clotting and works closely with vitamin K. if you want to know more about this amino acid then you may need to do a broader study and get your facts right.