[Home]Vitamin K

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Vitamin K is a group of 2-methilo-naphthoquinone derivatives.

It is a human vitamin, lipophilic? (i.e. soluble in lipids) and therefore hydophobic? (i.e. insoluble in water). It is required for [blood coagulation]?.

Normally it is produced by bacteral processes in the intestines, so insufficient intake is not known, unless the intestines are heavily damaged.

Vitamin K is involved in the formation of calcium-binding groups in proteins. These calcium-binding groups are called Gla-residues, and the proteins containing these residues are designated as Gla-proteins. The Gla-residues are essential for the biological activity of all Gla-proteins. At this time not more than 12 human Gla-proteins have been discovered, and they play key roles in the regulation of three physiological processes: 1. blood coagulation, 2. bone metabolism, and 3. vascular biology.

Vitamin K-deficiency may occur by either nutritional vitamin K-deficiency, disturbed intestinal uptake (e.g. caused by a bile duct obstruction), or by therapeutical or accidental intake of vitamin K-antagonists. As a result of the acquired vitamin K-deficiency, Gla-residues are not or incompletely formed and hence the Gla-proteins are inactive. Lack of control of the three processes mentioned above may lead to: risk of uncontrolled and massive bleeding, cartilage calcification and severe malformation of developing bone, or deposition of insoluble calcium salts in the arterial vessel walls.

Discovery of vitamin K

In the late 1920's the Danish scientist Henrik Dam investigated the role of cholesterol by feeding chickens with a cholesterol-depleted diet. After several weeks the animals developed hemorrhages and started bleeding. These defects could not be restored by adding purified cholesterol to the diet. It appeared that - together with the cholesterol - a second compound had been extracted from the food, and this compound was called the coagulation vitamin. The new vitamin received the letter K because the initial discoveries were reported in a German journal, in which it was designated as Koagulations Vitamin.

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. The extent to which blood coagulation was restored by the diet was taken as a measure for its vitamin K content.

The precise function of vitamin K was not discovered before 1974, when the vitamin K-dependent coagulation factor prothrombin was isolated from cows which had received a high dose of the vitamin K-antagonist warfarin. It was shown that normal prothrombin contained 10 unusual amino acid residues which were identified as g-carboxyglutamate (abbreviation: Gla). 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.

Discovery of Gla-proteins

Until now 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 (Gas6), and the proline-rich Gla-proteins (PRGP’s) the function of which is presently unknown. In all cases in which their function was known, the presence of the Gla-residues in these proteins turned out to be essential for functional activity.

Gla-proteins occur in a wide variety of vertebrates: mammals, birds, reptiles, and fish. A number of Australian snakes have been discovered the venom of which acts by activating the human blood clotting system. Remarkably, in some cases activation was accomplished by Gla-proteins capable of binding to phospholipid membranes and subsequent conversion of procoagulant clotting factors into activated ones.

Another interesting class of invertebrate Gla-proteins is formed by the conantokins, produced by the fish-hunting snail Conus Geographus. These snails produce a neurotoxin containing a variety of extremely Gla-rich proteins, which are sufficiently powerful to kill an adult man.

Structures of K-vitamins

Vitamin K is a group name for a number of related compounds, which have in common a methylated naphthoquinone ring structure, and which vary in the aliphatic side chain attached at the 3-position (see figure 1). Phylloquinone (also known as vitamin K1) invariably contains in its side chain four isoprenid residues one of which is unsaturated.

Menaquinones have side chains composed of a variable number of unsaturated isoprenoid residues; generally they are designated as MK-n, where n specifies the number of isoprenoids.

It is generally accepted that the naphthoquinone is the functional group, so that the mechanism of action is similar for all K-vitamins. Substantial differences may be expected, however, with respect to intestinal absorption, transport, tissue distribution, and bio-availability. These differences are caused by the different lipophilicity of the various side chains, and by the different food matrices in which they occur.

Figure 1: Chemical structures of vitamin K1 (phylloquinone, upper structure) and vitamin K2 (menaquinones, lower structure). Both contain a functional naphtoquinone ring and an aliphatic side chain. Phylloquinone has a phytyl side chain, whereas in menaquinone the side chain is composed of a varying number of isoprenoid residues.

"Vitamin K" is also a slang term for the drug Ketamine.

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Last edited December 16, 2001 1:35 am by Robbe (diff)