In 1929, Danish scientist Henrik Dam investigated the role of cholesterol by feeding chickens a cholesterol-depleted diet.[6]For several decades the vitamin K-deficient chick model was the only method of quantitating of vitamin K in various foods: the chicks were made vitamin K-deficient and subsequently fed with known amounts of vitamin K-containing food.
Function in the cell
The precise function of vitamin K was not discovered until 1974, when three laboratories (Stenflo et al.[10][12]) isolated the vitamin K-dependent coagulation factor prothrombin (Factor II) from cows that received a high dose of a vitamin K antagonist, warfarin. The extra carboxyl group in Gla made clear that vitamin K plays a role in a carboxylation reaction during which Glu is converted into Gla.
Within the cell, Vitamin K undergoes electron reduction to a reduced form of Vitamin K (called Vitamin K hydroquinone) by the enzyme Vitamin K epoxide reductase (or VKOR).[13]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. Vitamin K epoxide is then re-converted to Vitamin K by the Vitamin K epoxide reductase. These two enzymes comprise the so-called Vitamin K cycle.[16]Warfarin and other coumadin drugs block the action of the Vitamin K epoxide reductase.[17]See Warfarin.
Gla-proteins
At present, the following human Gla-containing proteins have been characterized to the level of primary structure: the blood coagulation factors II (prothrombin), VII, IX, and X, the anticoagulant proteins C and S, and the Factor X-targeting protein Z. The bone Gla-protein osteocalcin, the calcification inhibiting matrix gla protein (MGP), the cell growth regulating growth arrest specific gene 6 protein (Gas6), and the four transmembrane Gla proteins (TMGPs) the function of which is at present unknown. Remarkably, in some cases activation is accomplished by snake Gla-containing enzymes that bind to the endothelium of human blood vessels and catalyze the conversion of procoagulant clotting factors into activated ones, leading to unwanted and potentially deadly clotting.
Another interesting class of invertebrate Gla-containing proteins is synthesized by the fish-hunting snail Conus geographus.[18]Several of the conotoxins contain 2-5 Gla residues.[19]
Function in Bacteria
Many bacteria, such as Escherichia coli found in the large intestine, can synthesize Vitamin K2 (menaquinone),[20] but not Vitamin K1 (phylloquinone). In these bacteria, menaquinone will transfer two electrons between two different small molecules, in a process called anaerobic respiration.[21]The menaquinone, with the help of another enzyme, will in turn transfer these 2 electrons to a suitable oxidant, such fumarate or nitrate (also called an electron acceptor). Escherichia coli can carry out aerobic respiration and menaquninone-mediated anaerobic respiration.
Function in the cell
The precise function of vitamin K was not discovered until 1974, when three laboratories (Stenflo et al.[10][12]) isolated the vitamin K-dependent coagulation factor prothrombin (Factor II) from cows that received a high dose of a vitamin K antagonist, warfarin. The extra carboxyl group in Gla made clear that vitamin K plays a role in a carboxylation reaction during which Glu is converted into Gla.
Within the cell, Vitamin K undergoes electron reduction to a reduced form of Vitamin K (called Vitamin K hydroquinone) by the enzyme Vitamin K epoxide reductase (or VKOR).[13]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. Vitamin K epoxide is then re-converted to Vitamin K by the Vitamin K epoxide reductase. These two enzymes comprise the so-called Vitamin K cycle.[16]Warfarin and other coumadin drugs block the action of the Vitamin K epoxide reductase.[17]See Warfarin.
Gla-proteins
At present, the following human Gla-containing proteins have been characterized to the level of primary structure: the blood coagulation factors II (prothrombin), VII, IX, and X, the anticoagulant proteins C and S, and the Factor X-targeting protein Z. The bone Gla-protein osteocalcin, the calcification inhibiting matrix gla protein (MGP), the cell growth regulating growth arrest specific gene 6 protein (Gas6), and the four transmembrane Gla proteins (TMGPs) the function of which is at present unknown. Remarkably, in some cases activation is accomplished by snake Gla-containing enzymes that bind to the endothelium of human blood vessels and catalyze the conversion of procoagulant clotting factors into activated ones, leading to unwanted and potentially deadly clotting.
Another interesting class of invertebrate Gla-containing proteins is synthesized by the fish-hunting snail Conus geographus.[18]Several of the conotoxins contain 2-5 Gla residues.[19]
Function in Bacteria
Many bacteria, such as Escherichia coli found in the large intestine, can synthesize Vitamin K2 (menaquinone),[20] but not Vitamin K1 (phylloquinone). In these bacteria, menaquinone will transfer two electrons between two different small molecules, in a process called anaerobic respiration.[21]The menaquinone, with the help of another enzyme, will in turn transfer these 2 electrons to a suitable oxidant, such fumarate or nitrate (also called an electron acceptor). Escherichia coli can carry out aerobic respiration and menaquninone-mediated anaerobic respiration.
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