**Author details**

translate to a weakened anti‐inflammatory potential in the CKD patient and the CKD cat. The role of vitamin K in the homeostatic physiology of the kidney and the pathophysiology of

As with the ageing dog, cats are also likely to present with degenerative joint diseases [129] and the high co‐morbidity relationship with CKD suggests that vitamin K deficiency in the ageing cat is possible [130]. The function of vitamin K in the aetiology of feline degenerative

Vitamin K in animals as a general subject has not been systematically investigated. There are, however, common vitamin K‐related health issues that animals share with man. These are predominantly associated with coagulopathies, but diseases of the musculoskeletal system and kidney injury may have considerable overlaps to the mutual benefit of man and

The requirements for animal health and well‐being are poorly defined for vitamin K, with, in some cases, misconceptions about the contributions to vitamin K status from colonic bacterial sources. Animals may have a distinctly greater reliance on vitamin K2, in large part due to their diet, which is regulated by the feed that is given to them. Furthermore, the upper alimentary canal supply of menaquinones may be of central benefit to support the vitamin K status of several species such as ruminants and possibly in particular rabbit

An exciting emerging area is the molecular regulation embryological development and growth by the *in situ* generation of the vitamin K2 congener menaquinone‐4, through the prenyltransferase UBIAD1. The work on the zebrafish has the potential to radiate across all species, and this may be of particular importance in conservation breeding programmes.

There is reason to suspect that in some metabolic and inflammatory diseases, there is a pronounced vitamin K deficiency. The prospect of intervening in some of these pathologies with vitamin K, such as kidney disease, is already being proposed for human patients. Defining the vitamin K requirements in different animals, beyond simple hepatic coagulation factor needs, may suggest newer approaches to veterinary medicine that could be investi‐

This work was facilitated, in part, by the award of a senior fellowship to SJH by The Northern

feline CKD has not been the subject of focused study.

joint diseases remains to be investigated.

**5. Concluding remarks**

226 Vitamin K2 - Vital for Health and Wellbeing

animals.

kittens.

gated.

**Acknowledgements**

Norway Regional Health Authority.

Jayde O'Neil1 , Bethany Scarrott1 , Ragnhild Aven Svalheim2 , Jonathan Elliott1 and Stephen J. Hodges1,3\*


3 Anesthesia and Critical Care Research Group, The University Hospital of North Norway and UIT‐The Arctic University of Norway, Tromsø, Norway

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**Section 6**

**Biosynthesis of Vitamin K2 and Various**

**Metabolic Effects**


**Biosynthesis of Vitamin K2 and Various Metabolic Effects**

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**Chapter 13**

**Provisional chapter**

**Medicinal Chemistry of Vitamin K Derivatives and**

Vitamin K acts as a cofactor for γ‐glutamyl carboxylase. Recently, various biological activities of vitamin K have been reported. Anti‐proliferative activities of vitamin K, especially in vitamin K3, are well known. In addition, various physiological and pharmacological functions of vitamin K2, such as transcription modulators as nuclear steroid and xenobiotic receptor (SXR) ligands and anti‐inflammatory effects, have been revealed in the past decade. Characterization of vitamin K metabolites is also important for clinical application of vitamin K and its derivatives. In this chapter, recent progress on the medicinal chemistry of vitamin K derivatives and metabolites is discussed.

**Keywords:** vitamin K derivative, metabolite, antitumor activity, anti‐inflammatory ac‐

Vitamin K is a specific cofactor for γ‐glutamyl carboxylase (GGCX), which catalyzes formation of γ‐carboxyglutamyl (Gla) residues in vitamin K–dependent proteins (**Figure 1**) [1]. Various other biological activities of vitamin K and its derivatives have also been reported. For example, vitamin K3 (menadione), a vitamin K homologue that was considered as a synthetic vitamin K, has antitumor activity [2–5], as does vitamin K2 (menaquinone) [6, 7]. Among the homologues of vitamin K2, menaquinone‐4 (MK‐4), which contains four isoprene units, has been intensively investigated. It binds to nuclear receptor human pregnane X receptor (PXR), which is also called steroid and xenobiotic receptor (SXR), and regulates transcription of osteoblastic genes [8, 9]. It also exhibits anti‐inflammatory activity by suppressing the NF‐kB pathway [10], and has an inhibitory effect on arteriosclerosis [11]. It binds 17β‐hydroxysteroid dehydrogenase 4 and

and reproduction in any medium, provided the original work is properly cited.

© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

tivity, steroid and xenobiotic receptor/pregnane X receptor

**Medicinal Chemistry of Vitamin K Derivatives and**

**Metabolites**

**Metabolites**

Shinya Fujii and Hiroyuki Kagechika

Shinya Fujii and Hiroyuki Kagechika

http://dx.doi.org/10.5772/63511

**Abstract**

**1. Introduction**

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

#### **Medicinal Chemistry of Vitamin K Derivatives and Metabolites Medicinal Chemistry of Vitamin K Derivatives and Metabolites**

Shinya Fujii and Hiroyuki Kagechika Shinya Fujii and Hiroyuki Kagechika

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/63511

#### **Abstract**

Vitamin K acts as a cofactor for γ‐glutamyl carboxylase. Recently, various biological activities of vitamin K have been reported. Anti‐proliferative activities of vitamin K, especially in vitamin K3, are well known. In addition, various physiological and pharmacological functions of vitamin K2, such as transcription modulators as nuclear steroid and xenobiotic receptor (SXR) ligands and anti‐inflammatory effects, have been revealed in the past decade. Characterization of vitamin K metabolites is also important for clinical application of vitamin K and its derivatives. In this chapter, recent progress on the medicinal chemistry of vitamin K derivatives and metabolites is discussed.

**Keywords:** vitamin K derivative, metabolite, antitumor activity, anti‐inflammatory ac‐ tivity, steroid and xenobiotic receptor/pregnane X receptor
