Menatetrenone

Pharmacokinetic dataBioavailabilityLow (oral)^[1]IdentifiersCAS NumberPubChem CIDChemSpiderUNIIKEGGChEBICompTox Dashboard (EPA)Chemical and physical dataFormulaC₃₁H₄₀O₂Molar mass444.659 g·mol⁻¹3D model (JSmol) ^NY (what is this?)  (verify)

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

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 – discuss]}

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

• Removal of the phytyl tail to form menadione (K3; unknown enzyme);
• Reduction of menadione to menadiol (likely NQO1);
• Attachment of GGPP tail to form menaquinol-4, the reduced form of MK-4 (UBIAD1)

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

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]

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]