Menatetrenone

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Menatetrenone
Menatetrenone.svg
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
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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 – discuss ]

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]

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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