Vitamin K

Chemical structure

All members of the vitamin K group of vitamins share a isoprenoid 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.

Physiology

Vitamin K is involved in the calcium. The Gla-residues are essential for the biological activity of all known Gla-proteins.^[1]

At this time 14 human proteins with Gla domains have been discovered, and they play key roles in the regulation of three physiological processes:

• protein Z).^[2]
• Bone metabolism: osteocalcin, also called bone Gla-protein (BGP), and matrix gla protein (MGP).^[3]
• Vascular biology.^[4]

Recommended amounts

The U.S. Dietary Reference Intake (DRI) for an Adequate Intake (AI) for a 25-year old male for Vitamin K is 120 micrograms/day. No Tolerable Upper Intake Level (UL) has been set. The human body stores Vitamin K, so it is not necessary to take Vitamin K daily^{[citation needed]}.

Sources of Vitamin K

Vitamin K is found in leafy green vegetables such as spinach and lettuce; Brassica vegetables such as kale, cabbage, cauliflower, broccoli, and Brussels sprouts; parsley contains 153% of the recommended daily amount of vitamin K.^[5]Olive oil contains a large amount of vitamin K.

Phylloquinone (vitamin K1) is the major dietary form of vitamin K. Vitamin K₁ is found in chicken egg yolk, butter, cow liver, and most cheeses. It is also found in most types of mayonnaise.

Role in disease

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 massive, uncontrolled internal bleeding, cartilage calcification and severe malformation of developing bone, or deposition of insoluble calcium salts in the arterial vessel walls. The deposition of calcium in soft tissues, including arterial walls, is quite common, especially in those suffering from artherosclerosis, suggesting that Vitamin K defficiency is more common than previously thought (see reference 4).

Use on newborn babies

In some countries, injections of Vitamin K are routinely given to newborn babies. Vitamin K is used as prophylactic measure to prevent late-onset haemorrhagic disease (HDN). However, HDN is a relatively rare problem, and many parents now choose for their babies not to have such an injection.

Biochemistry

Discovery

In 1929, Danish scientist cholesterol by feeding chickens a cholesterol-depleted diet.^[6] 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 Koagulationsvitamin. Edward Adelbert Doisy (of Saint Louis University) did much of the research that led to the discovery of the structure and chemical nature of Vitamin K.^[7] Dam and Doisy shared the 1943 Nobel Prize for medicine for their work on Vitamin K. Several laboratories synthesized the compound in 1939.^[8]

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 first published report of successful treatment with vitamin K of life-threatening hemorrhage in a jaundiced patient with prothrombin deficiency was made in 1938 at the University of Iowa Department of Pathology by Drs. Harry Pratt Smith, Emory Warner, Kenneth Brinkhous, and Walter Seegers.^[9]

Function in the cell

The precise function of vitamin K was not discovered until 1974, when three laboratories (Stenflo et al.^[10], Nelsestuen et al.^[11], and Magnusson et al.^[12]) isolated the vitamin K-dependent coagulation factor amino acid residues near the amino terminus of this protein, the normal (untreated) cows contained 10 unusual residues which were chemically identified as gamma-carboxyglutamate, or Gla. 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.

The biochemistry of how Vitamin K is used to convert Glu to Gla has been elucidated over the past thirty years in academic laboratories throughout the world. Within the cell, Vitamin K undergoes electron Vitamin K epoxide reductase. These two enzymes comprise the so-called Vitamin K cycle.^[16] One of the reasons why Vitamin K is rarely deficient in a human diet is because Vitamin K is continually recycled in our cells.

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 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 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] These snails produce a venom containing hundreds of neuro-active peptides, or conotoxins, which is sufficiently toxic to kill an adult human. 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 anaerobic respiration.

Carcinogenicity

Vitamin K substances are IARC Group 3 carcinogens. One study conducted in the United Kingdom found a nearly two-fold increase of leukaemia in children administered Vitamin K intramuscularly. ^[22]

References

Further reading

• Dam, H., Researches in Vitamin K, In: Pespectives in Biological Chemistry (RE Olson, ed.), Marcel Dekker, 1970. The Nobel Prize winner recounts the history of the discovery of Vitamin K.
• Suttie, J.W., Vitamin K, In: Handbook of Lipid research: The fat-soluble vitamins (HF DeLuca, ed.), Plenum Press, 1978. Outstanding review of Vitamin K research from 1930-1978 by one of the leaders in the field.
• David A. Bender, Nutritional biochemistry of the vitamins, Cambridge University Press, 2003
• G. F. M. Ball, Vitamins: their role in the human body, Blackwell Science, 2004
• Gerald F. Combs, The vitamins: fundamental aspects in nutrition and health, Academic Press, 1998

v • d • e Choline

v • d • e Types of Zinc