A complete Look at Vitamin K

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A Complete Look at Vitamin K

Vitamin K is a group name for a number of related compounds. They are a group of 2-methilo-naphthoquinone derivatives that are human vitamins. They are lipophilic (i.e. soluble in lipids) and therefore hydrophobic (i.e. poorly soluble in water). They are needed for the posttranslational modification of certain proteins, mostly required for blood coagulation.

Vitamin K is involved in the carboxylation of certain glutamate residues in proteins to form gamma-carboxyglutamate residues (abbreviated Gla-residues) Gla-residues are usually involved in the process of binding calcium. The Gla-residues are essential for the biological activity of all known Gla-proteins. Currently there are 14 human Gla-proteins that have been discovered and they play key roles in the regulation of three processes:
Blood coagulation, bone metabolism and vascular biology.

For a 25 year old male, the recommended intake according to the U. S. Dietary Reference Intake (DRI) for Vitamin K is 12- micrograms per day. There is no tolerable upper level intake set.

History

Danish scientist Henrik Dam investigated the role of cholesterol in a late 1920 study. He feed chickens a cholesterol-depleted diet. After a few weeks, the chickens developed hemorrhages and started to bleed. Purified cholesterol was added to their diet, but still the defects could not be restored. This indicates together with the cholesterol- a second compound had to be extracted from the food. This compound was called the coagulation vitamin. This new vitamin them received the letter K because the initial discoveries were reported in the German journal, in which it was designated as Koagulations Vitamin. Much of the research done that led to the discovery of the structure and chemical nature of Vitamin K was done by Edward Adelberty Doisy of Saint Louis University. Dam and Doisy received the 1943 Nobel Price for medicine for their works on Vitamin K.

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 then later fed with known amounts of vitamin-k containing food. The extent to which blood coagulation was restored by the diet was taken as a measure for its vitamin K content.

The function of vitamin K was discovered in 1974. The vitamin K-dependent coagulation factor prothrombin (Factor II) was isolated from cows that had received high doses of vitamin K antagonist warfarin. It was shown that normal prothombin contained 10 unusual amino acid residues which were identified as gamma-carboxglutamate. Prothrombin isolated from warfarin-treated cows had normal glutamate at the Gla-positions and was designated as descarboxyprothrombin. 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.
Gla-proteins

Gla-proteins are known to occur in a wide variety of vertebrates: mammals, birds, reptiles and fish.

Presently, the following human Gla-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 thrombin-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 (Gas 6), and the four transmembrane Gla proteins (TMGPs) the function which is currently unknown. Gas 6 can function as a growth factor that activates the Axl receptor tyrosine kinase and stimulates cell proliferation or prevents apoptosis in some cells. In many cases in which their function was known, the presence of the Gla-residues in proteins turned out to be essential for functional activity.

Deficiencies

Vitamin K deficiency may occur by disturbed intestinal uptake, by therapeutic or accidental intake of vitamin K-antagonists or very rarely by nutritional vitamin K deficiency. As a result of a deficiency, Gla-residues are not or incompletely formed and therefore, the Gla-proteins are inactive. Lack of regulation of blood coagulation, bone metabolism and vascular biology can lead to the following: risk of massive, uncontrolled internal bleeding, cartilage calcification and severe malformation of developing bone or deposition of insoluble calcium salts in the arterial vessel walls.