Vitamin K Discovery Of Vitamin K Discovery Of Gla proteins

Normally it is produced by bacteria in the intestines, and dietary deficiency is extremely rare unless the intestines are heavily damaged.

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 binding calcium. The Gla-residues are essential for the biological activity of all known Gla-proteins. At this time fewer than 12 human Gla-proteins have been discovered, and they play key roles in the regulation of three physiological processes:

Vitamin K-deficiency may occur by disturbed intestinal uptake (such as would occur in a bile duct obstruction), by therapeutic or accidental intake of vitamin K-antagonists or, very rarely, by nutritional vitamin K-deficiency. 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 the following: 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.

1 Discovery of vitamin K

In the late 1920s, Danish scientist Henrik Dam investigated the role of cholesterolCholesterol is a steroid lipid, found in the cell membranes of all body tissues, and transported in the blood plasma, of all animals. Most cholesterol is produced internally, not dietary in origin. It is present in higher concentrations in tissues which e by feeding chickens 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. Edward Adelbert Doisy (of Saint Louis UniversitySaint Louis University (SLU) is a private, co-educational Roman Catholic university in the United States. Located in Saint Louis, Missouri, it was founded in 1818 as Saint Louis Academy by the Society of Jesus. The first M. degree awarded west of the Miss) did much of the research that led to the discovery of the structure and chemical nature of Vitamin K. Dam and Doisy shared the 19431943 is the common year starting on Friday. Events January January 4 End of term for Culbert Olson, 29th Governor of California. He is succeeded by Earl Warren. January 11 The United States and United Kingdom give up territorial rights in China. January 1 Nobel PrizeThe Nobel Prizes (pronounced no-BELL or no-bell are awarded annually to people who have done outstanding research, invented groundbreaking techniques or equipment, or made outstanding contributions to society. It is generally regarded as the supreme comme for medicine for their work 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 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 until 19741974 is a common year starting on Tuesday (click on link for calendar). Events January-February January 5 Dungeons & Dragons officially released. February 4 Patricia Hearst, the 19 year old granddaughter of publisher William Randolph Hearst, is kidnapped, when the vitamin K-dependent coagulation factor prothrombin was isolated from cows which had received a high dose of the vitamin K-antagonist warfarinWarfarin (also known under the brand name Coumadin ) is an anticoagulant medication that can be given orally. Normally, vitamin K is converted to vitamin K epoxide in the liver. This epoxide is then reduced by the enzyme epoxide reductase. The reduced for. It was shown that normal prothrombin contained 10 unusual amino acid residues which were identified as gamma-carboxyglutamate. 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.

2 Discovery of Gla-proteins

At present, 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 growthThe term cell growth is used in two different ways in biology. When used in the context of reproduction of living cells the phrase "cell growth" is shorthand for the idea of "growth in cell numbers by means of cell reproduction. During cell reproduction o regulating growth arrest specific gene 6 protein (Gas6), and the proline-rich Gla-proteins (PRGPs) the function of which is at present unknown. Gas6 can function as a growth factor that activates the Axl receptor tyrosine kinase and stimulates cell proliferation or prevents apoptosis in some cells. 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 are known to occur in a wide variety of vertebrates: mammals, birds, reptiles, and fish. The venom of a number of Australian snakes 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 peptides, which are sufficiently powerful to kill an adult human.

3 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, left structure) and vitamin K2 (menaquinones, right structure). Both contain a functional naphthoquinone 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.

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