Menatetrenone

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Menatetrenone
Menatetrenone.PNG
Menatetrenone molecule spacefill.png
Clinical data
Other names3-methyl-2-[(2Z,6E,10E)-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraenyl]naphthalene-1,4-dione
AHFS/Drugs.com International Drug Names
Routes of
administration
By mouth
ATC code
Pharmacokinetic data
Bioavailability Low (oral) [1]
Identifiers
  • 2-methyl-3-[(2Z,6E,10E)-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraen-1-yl]naphthoquinone
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
CompTox Dashboard (EPA)
Chemical and physical data
Formula C31H40O2
Molar mass 444.659 g·mol−1
3D model (JSmol)
  • CC1=C(C(=O)C2=CC=CC=C2C1=O)C/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CCC=C(C)C
  • InChI=1S/C31H40O2/c1-22(2)12-9-13-23(3)14-10-15-24(4)16-11-17-25(5)20-21-27-26(6)30(32)28-18-7-8-19-29(28)31(27)33/h7-8,12,14,16,18-20H,9-11,13,15,17,21H2,1-6H3/b23-14+,24-16+,25-20+ X mark.svgN
  • Key:DKHGMERMDICWDU-GHDNBGIDSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Menatetrenone (INN), also known as menaquinone-4 (MK-4), is one of the nine forms of vitamin K2.

Contents

Biology

MK-4 is the major form of Vitamin K in vertebrate animals, including humans and common forms of meat animals. It is produced via conversion of vitamin K1 in the body, specifically in the testes, pancreas and arterial walls. [2] The conversion is not dependent on gut bacteria, occurring in germ-free rats [3] [4] and in parenterally-administered K1 in rats. [5] [6] Tissues that accumulate high amounts of MK-4 have a capacity to convert up to 90% of the available K1 into MK-4. [3] [4] [ dubious ]

K1 is converted to MK-4 in three steps: [7]

The second and third steps are known to happen in target tissue. The first step is proposed to happen mainly in the intestines. [7]

As a medication

Menatetrenone is approved in Japan for second-line treatment of postmenopausal osteoporosis. Evidence is restricted to small-scale RCTs; the minimum effective dose (for bone mass parameters) is 45 mg, much higher than the Daily Value for vitamin K (80 μg). [8]

Bioavailbility and dose

420 μg of oral MK-4, in a single-dose or spread out over 7 days, does not cause detectable changes in serum MK-4 level in healthy women, whereas MK-7 produces the expected increases in MK-7 levels. [1]

The minimum effective oral dose to change serum osteocalcin levels is 1500 μg/d, where as oral MK-7 is effective on this parameter at 45 μg/d, a level more in line with nutritional intake. In addition, rat studies show that oral MK-7 is better at increasing extrahepatic tissue levels of MK-4 than oral MK-4. [1]

Related Research Articles

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Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone sterility, and consequent increase in fracture risk. It is the most common reason for a broken bone among the elderly. Bones that commonly break include the vertebrae in the spine, the bones of the forearm, the wrist, and the hip. Until a broken bone occurs there are typically no symptoms. Bones may weaken to such a degree that a break may occur with minor stress or spontaneously. After the broken bone heals, the person may have chronic pain and a decreased ability to carry out normal activities.

<span class="mw-page-title-main">Vitamin K</span> Fat-soluble vitamers

Vitamin K is a family of structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-synthesis modification of certain proteins that are required for blood coagulation or for controlling binding of calcium in bones and other tissues. The complete synthesis involves final modification of these so-called "Gla proteins" by the enzyme gamma-glutamyl carboxylase that uses vitamin K as a cofactor.

<span class="mw-page-title-main">Cholecalciferol</span> Vitamin D3, a chemical compound

Cholecalciferol, also known as vitamin D3 and colecalciferol, is a type of vitamin D that is made by the skin when exposed to sunlight; it is found in some foods and can be taken as a dietary supplement.

β-Carotene Red-orange pigment of the terpenoids class

β-Carotene (beta-carotene) is an organic, strongly coloured red-orange pigment abundant in fungi, plants, and fruits. It is a member of the carotenes, which are terpenoids (isoprenoids), synthesized biochemically from eight isoprene units and thus having 40 carbons. Among the carotenes, β-carotene is distinguished by having beta-rings at both ends of the molecule. β-Carotene is biosynthesized from geranylgeranyl pyrophosphate.

<span class="mw-page-title-main">Hypervitaminosis A</span> Toxic effects of ingesting too much vitamin A

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<span class="mw-page-title-main">Vitamin D toxicity</span> Human disease

Vitamin D toxicity, or hypervitaminosis D is the toxic state of an excess of vitamin D. The normal range for blood concentration in adults is 20 to 50 nanograms per milliliter (ng/mL).

<span class="mw-page-title-main">Menadione</span> Chemical compound

Menadione is a natural organic compound with the formula C6H4(CO)2C2H(CH3). It is an analog of 1,4-naphthoquinone with a methyl group in the 2-position. It is sometimes called vitamin K3. Use is allowed as a nutritional supplement in animal feed because of its vitamin K activity.

<span class="mw-page-title-main">Phytomenadione</span> Chemical compound

Phytomenadione, also known as vitamin K1 or phylloquinone, is a vitamin found in food and used as a dietary supplement. It is on the World Health Organization's List of Essential Medicines.

Vitamin B<sub><small>12</small></sub> Vitamin used in animal cells metabolism

Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, and in both fatty acid and amino acid metabolism. It is important in the normal functioning of the nervous system via its role in the synthesis of myelin, and in the circulatory system in the maturation of red blood cells in the bone marrow. Plants do not need cobalamin and carry out the reactions with enzymes that are not dependent on it.

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Vitamin K deficiency results from insufficient dietary vitamin K1 or vitamin K2 or both.

<span class="mw-page-title-main">Vitamin D deficiency</span> Human disorder

Vitamin D deficiency or hypovitaminosis D is a vitamin D level that is below normal. It most commonly occurs in people when they have inadequate exposure to sunlight, particularly sunlight with adequate ultraviolet B rays (UVB). Vitamin D deficiency can also be caused by inadequate nutritional intake of vitamin D; disorders that limit vitamin D absorption; and disorders that impair the conversion of vitamin D to active metabolites, including certain liver, kidney, and hereditary disorders. Deficiency impairs bone mineralization, leading to bone-softening diseases, such as rickets in children. It can also worsen osteomalacia and osteoporosis in adults, increasing the risk of bone fractures. Muscle weakness is also a common symptom of vitamin D deficiency, further increasing the risk of fall and bone fractures in adults. Vitamin D deficiency is associated with the development of schizophrenia.

<span class="mw-page-title-main">Vitamin K reaction</span> Medical condition

Vitamin K reactions are adverse side effects that may occur after injection with vitamin K. The liver utilizes vitamin K to produce coagulation factors that help the body form blood clots which prevent excessive bleeding. Vitamin K injections are administered to newborns as a preventative measure to reduce the risk of hemorrhagic disease of the newborn (HDN).

<span class="mw-page-title-main">Vitamin D</span> Group of fat-soluble secosteroids

Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and for many other biological effects. In humans, the most important compounds in this group are vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol).

<span class="mw-page-title-main">Trimegestone</span> Chemical compound

Trimegestone, sold under the brand names Ondeva and Totelle among others, is a progestin medication which is used in menopausal hormone therapy and in the prevention of postmenopausal osteoporosis. It was also under development for use in birth control pills to prevent pregnancy, but ultimately was not marketed for this purpose. The medication is available alone or in combination with an estrogen. It is taken by mouth.

<span class="mw-page-title-main">Menadiol</span> Chemical compound

Menadiol is an organic compound with the formula C6H4(COH)2(CH)(CH3). It is formally a derivative of p-hydroquinone. The name vitamin K4 can refer to:

Abaloparatide, sold under the brand name Tymlos among others, is a parathyroid hormone-related protein (PTHrP) analog medication used to treat osteoporosis. It is an anabolic agent.

Vitamin K<sub>2</sub> Group of vitamins and bacterial metabolites

Vitamin K2 or menaquinone (MK) is one of three types of vitamin K, the other two being vitamin K1 (phylloquinone) and K3 (menadione). K2 is both a tissue and bacterial product (derived from vitamin K1 in both cases) and is usually found in animal products or fermented foods.

<span class="mw-page-title-main">4-Amino-2-methyl-1-naphthol</span> Chemical compound

4-Amino-2-methyl-1-naphthol is a menadione analog. Its water-soluble hydrochloride (HCl) salt is often called vitamin K5. The HCl salt has been used as a medicine for vitamin K deficiency under tradenames such as Synkamin, which was sold by Parke-Davis, but has since been discontinued.

<span class="mw-page-title-main">2-Methylnaphthalene-1,4-diamine</span> Chemical compound

2-Methylnaphthalene-1,4-diamine is a synthetic menadione analog with vitamin K activity.

References

  1. 1 2 3 Sato T, Schurgers LJ, Uenishi K (November 2012). "Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women". Nutrition Journal. 11 (93): 93. doi: 10.1186/1475-2891-11-93 . PMC   3502319 . PMID   23140417.
  2. Shearer MJ, Newman P (October 2008). "Metabolism and cell biology of vitamin K". Thrombosis and Haemostasis. 100 (4): 530–47. doi:10.1160/TH08-03-0147. PMID   18841274. S2CID   7743991.
  3. 1 2 Davidson RT, Foley AL, Engelke JA, Suttie JW (February 1998). "Conversion of dietary phylloquinone to tissue menaquinone-4 in rats is not dependent on gut bacteria". The Journal of Nutrition. 128 (2): 220–3. doi: 10.1093/jn/128.2.220 . PMID   9446847.
  4. 1 2 Ronden JE, Drittij-Reijnders MJ, Vermeer C, Thijssen HH (January 1998). "Intestinal flora is not an intermediate in the phylloquinone-menaquinone-4 conversion in the rat". Biochimica et Biophysica Acta (BBA) - General Subjects. 1379 (1): 69–75. doi:10.1016/S0304-4165(97)00089-5. PMID   9468334.
  5. Thijssen HH, Drittij-Reijnders MJ (September 1994). "Vitamin K distribution in rat tissues: dietary phylloquinone is a source of tissue menaquinone-4". The British Journal of Nutrition. 72 (3): 415–25. doi: 10.1079/BJN19940043 . PMID   7947656.
  6. Will BH, Usui Y, Suttie JW (December 1992). "Comparative metabolism and requirement of vitamin K in chicks and rats". The Journal of Nutrition. 122 (12): 2354–60. doi: 10.1093/jn/122.12.2354 . PMID   1453219.
  7. 1 2 Shearer MJ, Newman P (March 2014). "Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis". Journal of Lipid Research. 55 (3): 345–362. doi: 10.1194/jlr.R045559 . PMC   3934721 . PMID   24489112.
  8. Iwamoto J (May 2014). "Vitamin K2 therapy for postmenopausal osteoporosis". Nutrients. 6 (5): 1971–80. doi: 10.3390/nu6051971 . PMC   4042573 . PMID   24841104. administered daily doses of 15, 45, 90, and 135 mg revealed that 45 mg was the minimum effective dose for improving bone mass parameters evaluated by microdensitometry and/or single photon absorptiometry in postmenopausal women with osteoporosis
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