Vitamin K Flashcards
Forms
K1- phylloquinone (plants)
K2- menaquinone n (n=4-13), (microorganisms)
K3- menadione (synthetic)
MD4 most common, produced by K1
Biosynthesis
VKD proteins involved in production of prothrombin. VK is cofactor for gamma-glutamylcarboxylase.
enzyme modifies VKD proteins, allowing them to bind to Ca, fold properly. necessary for function of coagulation/ anticoagulation factors
Vitamin K hydroquinone
get VK quinone from diet. reduced to hydroquinone by gamma- glutamylcarboxylase
used for carboxylation of Glu to Gla
Vitamin K epoxide
during carboxylation, hydroquinone –> epoxide –> back to hydroquinone (by VK epoxide reductase)
for active VKD proteins
** reductase steps are inhibited by coumarin based anticoagulants (warfarin)
VKD proteins
Factor II (prothrombin)
osteocalcin (calcified tissue)
matrix gla protein (MGP) – bone matrix, dentin, cartilage. (-) tissue calcification
** carboxylation is required for biological activity of VKD proteins @ gla domain. –> Ca binding, conformational change in protein
osteocalcin
a CaBP. if not carboxylated, cannot bind to hydroxyapatite.
synthesized in osteoblasts
biomarker for bone formation (morphogenesis)
Clinical use
anticoagulant drugs
also hemorrhagic disease of newborn, fat malabsorption, BMD/osteoporosis, ABX treatment
low VK –> low BMD
supplements dec levels of undercarboxylated osteocalcin
Assessment
Prothrombin time
international normalized Ratio, corrects for difference in thromboplastin sensitivities
PIVKA II. protein induced by VK absence factor II. serum concentration of under gamma carboxylated prothrombin
ucOC- under gamma carboxylated osteocalcin
Dietary recommendations if on coumadin
coumadin –> (-) VK –> depletion of VKD
need to maintain consistent intake of VK from food and supplements. sudden changes can inc/dec anticoagulant effects.
