Menatetrenone

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

Menatetrenone

Clinical data
Other names	3-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	M05BX08 (WHO)
Pharmacokinetic data
Bioavailability	Low (oral)[1]
Identifiers
IUPAC name 2-methyl-3-[(2Z,6E,10E)-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraen-1-yl]naphthoquinone
CAS Number	863-61-6 Y
PubChem CID	5282367
ChemSpider	4445530 N
UNII	27Y876D139
KEGG	D00100 Y
ChEBI	CHEBI:78277 N
CompTox Dashboard (EPA)	DTXSID6048969
Chemical and physical data
Formula	C31H40O2
Molar mass	444.659 g·mol−1
3D model (JSmol)	Interactive image
SMILES 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 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+ N Key:DKHGMERMDICWDU-GHDNBGIDSA-N N
NY (what is this?)  (verify)

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 – 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]

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]