Relationship between Structure and Biological Activity of Various Vitamin K Forms

Abstract

Vitamin K is involved many biological processes, such as the regulation of blood coagulation, prevention of vascular calcification, bone metabolism and modulation of cell proliferation. Menaquinones (MK) and phylloquinone vary in biological activity, showing different bioavailability, half-life and transport mechanisms. Vitamin K1 and MK-4 remain present in the plasma for 8-24 h, whereas long-chain menaquinones can be detected up to 96 h after administration. Geometric structure is also an important factor that conditions their properties. Cis-phylloquinone shows nearly no biological activity. An equivalent study for menaquinone is not available. The effective dose to decrease uncarboxylated osteocalcin was six times lower for MK-7 than for MK-4. Similarly, MK-7 affected blood coagulation system at dose three to four times lower than vitamin K1. Both vitamin K1 and MK-7 inhibited the decline in bone mineral density, however benefits for the occurrence of cardiovascular diseases have been observed only for long-chain menaquinones. There are currently no guidelines for the recommended doses and forms of vitamin K in the prevention of osteoporosis, atherosclerosis and other cardiovascular disorders. Due to the presence of isomers with unknown biological properties in some dietary supplements, quality and safety of that products may be questioned.

Keywords: bone metabolism; menaquinone; phylloquinone; vascular calcification; vitamin K.

Figure 1

Chemical structures of different vitamin K forms.

Figure 2

The vitamin K cycle. Vitamin K (quinone) is reduced to hydroquinone by QR1 or VKOR. Then, during carboxylation of Glu to Gla, it serves as an electron donor and undergoes oxidation to 2,3-epoxide. Finally, it is converted back to quinone by VKOR. Abbreviations: QR1, quinone reductase; VKOR, vitamin K epoxide reductase; Glu, glutamic acid; Gla, γ-carboxyglutamic acid.

Figure 3

Menaquinone pathways of action associated with bone metabolism. Menaquinone is cofactor for GGCX, which catalyses activation of OC. Vitamin K2 also inhibits NF-κB activation induced by cytokines (RANKL, TNFα), which leads to inhibition of osteoclastogenesis and activation of osteoblastogenesis. Another mechanism includes activation of nuclear receptor PXR in osteoblasts, which increases expression of genes encoding bone matrix proteins. Abbreviations: RANKL, receptor activator of nuclear factor kappa-Β ligand; TNFα, tumour necrosis factor alpha; NF-κB, nuclear factor-kappa B; AP, alkaline phosphatase; PXR, pregnane X receptor; OC, osteocalcin; Gla-OC, carboxylated osteocalcin.