VITAMIN K - PHYTOMENADIONE

Vitamin K - Phytomenadione

Definition, structure and chemical forms

As per the definition of all substances called "vitamins", the phytomenadione it is a molecule that must be introduced into the organism from the outside, as the human body is unable to synthesize it from other molecules.

In reality, the term "vitamin K" refers to a together of molecules slightly different from each other but united by a basic structure (two condensed aromatic rings, with two ketone groups) which derives from 2-methyl-1,4-naphthoquinone, a molecule in turn derived from naphthalene. There are in fact three different forms of vitamin K:

  • Vitamin K1 o phylloquinone: the most represented in the diet and of plant origin. From the point of view of the chemical structure, it has a long unsaturated isoprenoid side chain starting from the C3 of the basic structure.

  • Vitamin K2: of bacterial origin. Among others, one of the producing bacteria is Escherichia Coli, normally present in the intestinal microbiota.

  • Vitamin K3 o menadione: synthetic origin, in fat-soluble or water-soluble form.

Vitamin K or phytomenadione

Chemical structure of vitamin K or phytomenadione

Sources of food intake and recommended dose

Where is Vitamin K found? Vitamin K is quite widespread within the food world, being present in significant quantities in various classes of foods and nutrients: vegetables, in particular vegetables (spinach, cabbage, broccoli, cabbage, turnip greens) and other fruits and vegetables. Other foods rich in vitamin K are legumes and eggs, and to a lesser extent also cereals, meat and dairy products.

In addition to exogenous (food) intake, the vitamin K that the body absorbs also derives from the production of intestinal bacterial flora.

According to the EFSA (European Food Safety Authority), an adequate dose of vitamin K is equal to 1 microgram per kg of body weight; however, there are no real studies that have been able to determine the amount of vitamin K produced by endogenous bacteria on the one hand and that present in food on the other, therefore the recommended dose is actually indicative.

Absorption, storage and metabolism

As a molecule fat soluble (due to the aromatic and isoprenoid chemical structure), vitamin K is absorbed according to the normal methods of absorption of fat. Therefore, its absorption occurs at the level of the intestine small intestine and colon (especially the K2), and is dependent on proper biliary and pancreatic function. In fact, in the presence of pancreatic juice (and therefore of the enzyme lipase) and of the bile secreted by the liver, vitamin K is emulsified and included in the transport structures (chylomicrons) that convey it to the liver. Here it is partly used, partly stored and partly included in the VLDL and LDL particles that transport it to the peripheral tissues.

In fact, in the body, vitamin K has a half-life (time interval in which its concentration is halved) of a few hours, so rather short; in fact, it is largely used immediately for the synthesis of some highly important molecules.

From the point of view of catabolism, vitamin K molecules undergo the process of β-oxidation and conjugation with glucuronic acid and are excreted in the urine.

Vegetable-foods-rich-vitamin-K

Vegetables, especially brassicas, are rich in vitamin K and should be taken with caution in people on oral anticoagulants such as warfarin.

Functions of Vitamin K

What is vitamin K used for? What is its function? After undergoing an activation process through an enzyme of the class of reductasi (with use of NADPH), vitamin K is transformed into a hydroquinone form; acts, in this form, as a cofactor in the process of γ-carboxylation of some important proteins.

There γ-carboxylation consists in the addition of a carboxyl group (COO) at the carbon level in the gamma position of an amino acid residue of glutamic acid, with the formation of gamma-carboxy-glutamic acid; thanks to the presence of two contiguous carboxyls (which in physiological conditions have a negative charge in the organism), a sort of "clamp" is formed which is able to strongly bind especially the calcium atoms (characterized by two positive charges): all this is at the basis of the importance of the γ-carboxylation process within the wider phenomenon of hemostasis and other functions performed by gamma-carboxylated proteins.

In particular, the proteins that undergo this particular process are:

  • Proteins involved in coagulation: coagulation factors such as factors VII, IX, X, prothrombin (factor II), protein C, protein S and protein Z

  • Osteocalcininvolved both in the organization of the bone and in some processes of memory formation

  • Transthyretin, transporter of the hormone thyroxine T4

  • Matrix gla protein (MGP), inhibitor of the deposit of minerals in the tissues

During the γ-carboxylation process, the active form of vitamin K - hydroquinone - is transformed into epoxide (highly unstable three-vertex cyclic ether). In this form it has no activity, and therefore a reconstitution mechanism through the enzyme is present in the human body vitamin K epoxide reductase (VKOR); the latter is the very important target of action of the warfarin, one of the main anticoagulants used in medicine.

Coagulation proteins

As for the proteins involved in the blood clotting, they belong to the extrinsic pathway (factor VII), the intrinsic pathway (factor IX) and the common pathway (factor X and prothrombin), and lead, once the coagulation cascade is activated, to the formation of the fibrin clot. Proteins C, S and Z are instead involved in the process that opposes blood coagulation: protein C, using protein S as a cofactor, is able to degrade factor V and factor VIII (both important cofactors for the coagulation process ) and therefore to block the activation of the coagulation cascade and the formation of clots; the role of protein Z is not fully known, but it probably acts in the degradation of factor Xa and XIa, as it acts as a cofactor for the protein Z - related protease inhibitor.

Osteocalcin

This protein is mainly produced by osteoblasts, cells responsible for the deposition of bone matrix. Therefore, it is used as a marker of bone metabolism: an increase indicates an increased deposition activity of bone matrix, and a decrease in the opposite.

Its synthesis depends not only on vitamin K, but also on vitamin D in active form (1.25 (OH)2 - cholecalciferol).

Transthyretin (TTR)

Previously called prealbumin, this protein is a transport molecule for thyroid hormones (especially important in the cerebrospinal fluid) and for retinol.

Transthyretin, having a half-life of about 3-5 days, is used as an index of medium-term malnutrition, while albumin (half-life of about 3 weeks) is a long-term index.

Deficiency and hypervitaminosis

Thanks to the high availability within the food world and the low quantity necessary for the organism, deficiency states are closely linked to particular conditions (early childhood, malabsorption problems, intake of anticoagulants), and are otherwise extremely rare.

vitamin K deficiency in early childhood it is favored by the poor transport capacity of the placenta towards this vitamin, by the absence of endogenous bacterial production in the newborn (due to sterility of the intestinal tract) and a possible reduced quantity present in breast milk. This deficiency can cause "classical haemorrhagic disease of the newborn" (VKDB), which has an incidence of 0.25 - 1.7 % but whose risk is almost eliminated by the administration of vitamin K1 or by supplementing the infant's diet. .

In the children and in adults, the deficiency may be due to a malabsorptive state due to various intestinal diseases (celiac disease, ulcerative colitis, cystic fibrosis), or to a liver problem with reduced bile production.

The manifestations resulting from a deficiency refer to the aforementioned proteins: hemorrhagic manifestations of various entities may therefore be present (from petechiae to intracranial hemorrhages), an osteoporotic state may establish (which sometimes precedes bleeding), and finally vascular calcifications may develop.

A bleeding state is normally investigated by testing PT (prothrombin time) e aPTT (activated partial thromboplastin time), which verify the efficacy of the activation of the extrinsic and intrinsic pathways of the coagulation cascade, respectively. In the case of vitamin K deficiency, although both activation pathways are involved (FVII and FIX, respectively the extrinsic and intrinsic pathways), the test that lengthens in duration is the prothrombin time, while the aPTT is, at least initially , of normal duration. This is due to the fact that factor VII has an extremely short half-life, and is therefore the first to decrease from a quantitative point of view; subsequently, the activated partial thromboplastin time will also be elevated.

As for a state of hypervitaminosis Kwhich can result in a overdose of supplements or Konakion, or excessive intake, it does not cause any pathological state in the case of vitamins K1 and K2, while one can be established haemolytic anemia due to the high oxidative stress caused by excesses of menadione (vitamin K3).

Vitamin K and drugs

As mentioned, one of the main anticoagulant drugs, the warfarin (trade name: Coumadin), is an inhibitor of the reconstitution of vitamin K, and through this mechanism it acts by preventing the correct development of the coagulation cascade. Warfarin is mainly used in conditions of atrial fibrillation and deep vein thrombosis to prevent life-threatening clots from forming. Contrary to what one might think, no correlation has been found between prolonged use of warfarin and a state of osteoporosis.

The working principle of warfarin is also exploited for the fact that it can be counteracted, in case of bleeding, by the administration of vitamin K (which therefore works as an antidote); for most other anticoagulant drugs, however, an antidote is not available.

Even states of vitamin K deficiency, and therefore the presence of bleeding, especially in the newborn, are easily treated with the administration of vitamin K.

The drug used is Konakion, which is vitamin K.1, and is administered as prophylaxis immediately after birth by intramuscular injection (1 mg) or by oral administration in drops (2 mg). It is also used as a food supplement in case of nutritional deficiency.

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