Menadione

Absorption

Variable and ranges from 10% to 80%

Toxicity

Menadione (vitamin K3), which is not used as a nutritional supplemental form of vitamin K for humans, has been reported to cause adverse reactions, including hemolytic anemia. Large doses have also been reported to cause brain damage.

Description

Vitamin K is a general term referring to a group of naphthoquinone derivatives required in the diet for blood clotting. Menadione is a fat-soluble vitamin that is essential for blood clotting. It is destroyed by irradiation during processing but has no appreciable loss during storage. It occurs in spinach, cabbage, liver, and wheat bran.

Chemical properties

Bright-yellow crystals with a very faint acrid odour. Insoluble in water; soluble in benzene (1 g/10 mL), ethanol (1 g/60 mL), and vegetable oils (1g/50 mL); moderately soluble in carbon tetrachloride and chloroform. Stable in air; decomposed by sunlight; destroyed by alkalis and reducing agents.

Physical properties

Appearance: phylloquinone is a yellow oil at room temperature, but the other vitamers K are yellow crystals. Solubility: the vitamers K and MK and most forms of menadione are insoluble in water, slightly soluble in ethanol, and readily soluble in ether, chloroform, fats, and oils. Stability: the vitamers K are sensitive to light and alkali, but are relatively stable to heat and oxidizing environments.
Menadione, the formal parent compound of the menaquinone series does not occur naturally but is a common synthetic form called menadione (2-methyl-1,4- naphthoquinone). This compound forms a water-soluble sodium bisulfite addition product, menadione sodium bisulfite, whose practical utility is limited by its instability in complex matrices such as feeds. However, in the presence of excess sodium bisulfite, it crystallizes as a complex with an additional mole of sodium bisulfite (i.e., menadione sodium bisulfite complex), which has greater stability, therefore, is used widely as a supplement to poultry feeds. A third water-soluble compound is menadione pyridinol bisulfite (MPB).

Originator

Kappaxin,Sterling Winthrop

The Uses of Menadione

Menadione is precursor to verious types of Vitamin K. It is of industrial importance as an intermediate in the synthesis of phylloquinone, and salts of its bisulfite adduct are used as stabilized forms in the animal feed industry. Commercially significant forms are menadione sodium bisulfite and menadione dimethyl pyrimidinol. Used as a micronutrient for livestock and pet foods.

What are the applications of Application

The primary known function of vitamin K is to assist in the normal clotting of blood, but it may also play a role in normal bone calcification. It is being incorporated into cosmetic preparations, particularly those used for treating dark circles. It could also be used in acne products, and there are studies underway on its efficacy for the treatment of spider veins.

Background

VK3 (2-methyl-1,4-naphthoquinone), is the synthetic precursor of all the naturally occurring vitamin K in the body. Vitamin K is necessary for the production of prothrombin and five other blood clotting factors in humans. The effects of menadione on cellular microtubules been examined ex vivo as well as its binding with purified tubulin and microtubules in vitro. Cell viability experiments using human cervical epithelial cancer cells (HeLa) and human oral epithelial cancer cells (KB) indicated that the IC(50) value for menadione is 25.6±0.6 and 64.3± 0.36 mM, respectively. In addition, menadione exhibits antiestrogenic activity on in vitro assay. Menadione also promotes the hepatic biosynthesis of blood clotting factors.

Indications

The primary known function of vitamin K is to assist in the normal clotting of blood, but it may also play a role in normal bone calcification.

What are the applications of Application

Vitamin K3 is an apoptotic inducer and Cdc2 (cdk1 inhibitor

Definition

ChEBI: Menadione is a member of the class of 1,4-naphthoquinones that is 1,4-naphthoquinone which is substituted at position 2 by a methyl group. It is used as a nutritional supplement and for the treatment of hypoprothrombinemia. It has a role as a nutraceutical, a human urinary metabolite, an angiogenesis inhibitor, an EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor and an antineoplastic agent. It is a member of 1,4-naphthoquinones and a vitamin K.

Indications

Vitamin K activity is associated with several quinones, including phylloquinone (vitamin K₁), menadione (vitamin K₃), and a variety of menaquinones (vitamin K₂). These quinones promote the synthesis of proteins that are involved in the coagulation of blood.These proteins include prothrombin, factor VII (proconvertin), factor IX (plasma thromboplastin). The vitamin K quinones are obtained from three major sources.Vitamin K is present in various plants, especially green vegetables. The menaquinones that possess vitamin K₂ activity are synthesized by bacteria, particularly gram-positive organisms; the bacteria in the gut of animals produce useful quantities of this vitamin.Vitamin K₃ is a chemically synthesized quinone that possesses the same activity as vitamin K₁.

Preparation

Menadione can be prepared by oxidizing 2-methylnaphthalene with chromic acid or hydrogen peroxide.

brand name

Kappaxin (Sterling Winthrop); Kayquinone.

Therapeutic Function

Prothrombogenic vitamin

General Description

Menadione is a prothrombogenic compound and belongs to the Vitamin K class of compounds, which are necessary for the biosynthesis of prothrombin and other blood clotting factors. It is used as a model quinone in cell culture and in vivo investigations. It is obtained as a catabolic product of phylloquinone and circulating precursor of tissue menaquinone-4 in rats.

Mechanism of action

Menadione, a vitamin K analogue, is a cofactor in the synthesis of factors II, VIl, IX, and X in the liver. Vitamin K analogues are required to play a role in the gamma carboxylation step of these factors so that they can bind Ca ions to the phospholipid surface, which is essential for the coagulation cascade reaction.

Hazard

Irritant to skin and mucous membranes, especially the alcoholic solution.

Biochem/physiol Actions

Menadione is an oxidative stress inducer.

Pharmacokinetics

Menadione is a fat-soluble vitamin precursor that is converted into menadione in the liver. It is produced primarily by bacteria in the pregut and intestines. This yellowish, synthetic crystalline substance is converted into the active form of the K2 vitamin in animals. A deficiency of vitamin K can be harmful, especially in infants who are prone to haemorrhage, as can an overdose. Newborns who consume too much vitamin K3 may develop kernicterus, a severe form of brain damage that can lead to reduced movement, loss of appetite, seizures, deafness, mental retardation and even death. This condition is associated with abnormally high concentrations of bilirubin (a bile pigment) in brain tissue, and the presence of K3 may lead to abnormally high concentrations of bilirubin. As a result, K3 is less used in medicine than it was previously.

Pharmacology

The typical role of vitamin K is to maintain normal blood coagulation function. Its role is related to the metabolic processes.

Clinical Use

Vitamin K deficiency results in increased bleeding time. This hypoprothrombinemia may lead to hemorrhage from the gastrointestinal tract, urinary tract, and nasal mucosa. In normal, healthy adults, deficiency is rare. The two groups at greatest risk are newborn infants and patients receiving anticoagulant therapy; hypoprothrombinemia preexists in these two groups. Any disease that causes the malabsorption of fats may lead to deficiency. Inhibition of the growth of intestinal bacteria from extended antibiotic therapy will result in decreased vitamin K synthesis and possible deficiency.

Side Effects

Toxicity of vitamin K has not been well defined. Jaundice may occur in a newborn if large dosages of vitamin K are given to the mother before birth. Although kernicterus may result, this can be prevented by using vitamin K.

Safety Profile

Poison by ingestion, intraperitoneal, and subcutaneous routes. Experimental teratogenic effects. Questionable carcinogen with experimental tumorigenic data. Human mutation data reported. When heated to decomposition it emits acrid smoke and irritating fumes.

Metabolism

The metabolism of menadione has been studied by Nishiyamaet al., and it is known that menadione undergoes a two-electron reduction by NAD (P)H:Quinone oxidoreductase 1 (NQO1) after which the reduced form of menadione (2-methyl-1,4-naphthalenediol, menadiol) is glucuronidated and excreted in urine.
1 and 0.1 mg doses of 2-methyl-1,4-naphthoquinone (menadione) labeled with C14 in the Me group were injected intramuscularly into mice. The animals were sacrificed at intervals of up to 30 h and the tissues were examined for radioactivity. Forty % of the injected activity left the site of injection in 15 min. The activity in the blood never exceeded 1% of the total amount injected. About 60% of the amount injected was excreted in the urine within 3 h. The activity in the bile and intestine reached a maximum value of about 5% of the total in 2–3 h.

Purification Methods

Recrystallise it from 95% EtOH, or MeOH after filtration. It forms bright yellow crystals which are decomposed by light. Its solubility in EtOH is 1.7% and in *C6H6 it is 10%. It IRRITATES mucous membranes and skin. [Fieser J Biol Chem 133 391 1940, Beilstein 7 IV 2430.]