TY - JOUR
T1 - New aspects of Vitamin K research with synthetic ligands
T2 - Transcriptional activity via SXR and Neural differentiation activity
AU - Hirota, Yoshihisa
AU - Suhara, Yoshitomo
N1 - Funding Information:
This work was partly supported by a Grant-in-aid for Scientific Research (C) [grant numbers 16K08325 and 17K00900, 18K11056] from the Japan Society for the Promotion of Science (JSPS) and a Fund for the Promotion of Joint International Research (Fostering Joint International Research (A)) [grant number 18KK0455] from the JSPS.
Funding Information:
Funding: This work was partly supported by a Grant-in-aid for Scientific Research (C) [grant numbers 16K08325 and 17K00900, 18K11056] from the Japan Society for the Promotion of Science (JSPS) and a Fund for the Promotion of Joint International Research (Fostering Joint International Research (A)) [grant number 18KK0455] from the JSPS.
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/6/2
Y1 - 2019/6/2
N2 - Vitamin K is classified into three homologs depending on the side-chain structure, with 2-methyl-1,4-naphthoqumone as the basic skeleton. These homologs are vitamin K1 (phylloquinone: PK), derived from plants with a phythyl side chain; vitamin K2 (menaquinone-n: MK-n), derived from intestinal bacteria with an isoprene side chain; and vitamin K3 (menadione: MD), a synthetic product without a side chain. Vitamin K homologs have physiological effects, including in blood coagulation and in osteogenic activity via γ-glutamyl carboxylase and are used clinically. Recent studies have revealed that vitamin K homologs are converted to MK-4 by the UbiA prenyltransferase domain-containing protein 1 (UBIAD1) in vivo and accumulate in all tissues. Although vitamin K is considered to have important physiological effects, its precise activities and mechanisms largely remain unclear. Recent research on vitamin K has suggested various new roles, such as transcriptional activity as an agonist of steroid and xenobiotic nuclear receptor and differentiation-inducing activity in neural stem cells. In this review, we describe synthetic ligands based on vitamin K and exhibit that the strength of biological activity can be controlled by modification of the side chain part.
AB - Vitamin K is classified into three homologs depending on the side-chain structure, with 2-methyl-1,4-naphthoqumone as the basic skeleton. These homologs are vitamin K1 (phylloquinone: PK), derived from plants with a phythyl side chain; vitamin K2 (menaquinone-n: MK-n), derived from intestinal bacteria with an isoprene side chain; and vitamin K3 (menadione: MD), a synthetic product without a side chain. Vitamin K homologs have physiological effects, including in blood coagulation and in osteogenic activity via γ-glutamyl carboxylase and are used clinically. Recent studies have revealed that vitamin K homologs are converted to MK-4 by the UbiA prenyltransferase domain-containing protein 1 (UBIAD1) in vivo and accumulate in all tissues. Although vitamin K is considered to have important physiological effects, its precise activities and mechanisms largely remain unclear. Recent research on vitamin K has suggested various new roles, such as transcriptional activity as an agonist of steroid and xenobiotic nuclear receptor and differentiation-inducing activity in neural stem cells. In this review, we describe synthetic ligands based on vitamin K and exhibit that the strength of biological activity can be controlled by modification of the side chain part.
KW - Derivatives research
KW - Neural differentiation action
KW - Steroid and xenobiotic receptor (SXR)
KW - UBIAD1
KW - Vitamin K
KW - ã-glutamyl carboxylase (GGCX)
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U2 - 10.3390/ijms20123006
DO - 10.3390/ijms20123006
M3 - Review article
C2 - 31226734
AN - SCOPUS:85068552628
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 12
M1 - 3006
ER -