vitamin K Flashcards
vitamin K aka
phylloquinone
2 features of vit K
- napthoquinon nucleus = gives it biological function
- fatty acid side chain = cause lipid-soluble and drives vit K to membranes
3 types of vit K
- phylloquinone
- menaquinones
- menadione
phylloquinone
vit K1
found in plants
menaquinones
vit K2
produced by bacteria
menadione
synthetic vit K
dietary source of vit K
dark leafy veg
is vit K requirement altered in pregnancy?
NO
2 locations of vit K absorption
- small intestine
- colon/lower digestive tract
__ in lower digestive tract synthesize vit L
bacteria in lower digestive tract synthesize vit K
vit K absorption rate in humans is __
vit K absorption rate in humans is highly variable
vit K absorption requires __
vit K absorption requires lipids
if there is an abundance of another lipid-soluble vitamin, such as vit __, this may __ the amount of vit K available in the absorbable micelle
if there is an abundance of another lipid-soluble vitamin, such as vit E, this may reduce the amount of vit K available in the absorbable micelle
2 methods of vit K absorption
passive diffusion
active transport
main absorption of vit K
passive diffusion
passive diffusion of vit K requires __ for emulsification, solubilization, and micelle formation
micelles __ into enterocyte
passive diffusion of vit K requires bile salts for emulsification, solubilization, and micelle formation
micelles passively diffuse into enterocyte
what do we know about active transport of vit K
nothing really
within enterocyte, vit K is put into
chylomicrons
once vit K is in chylomicrons,
- chylomicron released into lymph
- LPL degrades lipoprotein, vit K delivered to extra-hepatic tissues
- vit K in chylomicron remnants reach liver
vit K in liver
- liver stores some as menaquinone (bc it has slower turnover rate than phylloquinone)
- liver packs phylloquinone into VLDL, sends it to post-hepatic circulation
vit K in liver
- liver stores some as menaquinone (bc it has slower turnover rate than phylloquinone)
- liver packs phylloquinone into VLDL, sends it to post-hepatic circulation
why does the liver mainly store menaquinone
bc it has a slower turnover rate than phylloquinone
circulation form of vit K
phylloquinone
vit K in VLDL is
delivered to bone
where do we store vit K?
mostly in cell membrane of lung, kidneys, bone marrow
the liver __ vit K quickly, but __ very little
the liver metabolizes vit K quickly, but retains very little
excretion of vit K
- phylloquinone is oxidized and conjugated with glucouronic acid for defecation (feces and bile)
some urine
spped of turnover of body’s vit K pool
very fast
~1.5 days
all forms of vit K undergo __ __ to hydroquinone
all forms of vit K undergo reversible reduction to hydroquinone
biologically active vit K
hydroquinone
active form of vit K is __ after a vit K dependent rxn
active form of vit K is regenerated after a vit K dependent rxn
dietary form of vit K
vit K quinone (phylloquinone)
circulation form of vit K
vit K quinone
enzymes that use vit K as a cofactor
- gamma-glutamyl carboxylase (biosynthesis of vit K-dependent clotting factors)
gamma-glutamyl-carboxylated protein binds __
gamma-glutamyl-carboxylated protein binds Ca2+
warfarin inhibits __
warfarin inhibits vitamin K epoxide reductase (VKOR)
at high doses, warfarin also inhibits __
at high doses, warfarin also inhibits quinone reductases
2 enzymes that warfarin inhibits
VKOR
quinone reductases
when we stop inhibition caused by warfarin, we stop producing __ bc we block __ of vit K to reproduce __
when we stop inhibition caused by warfarin, we stop producing active vit K bc we block recycyling of vit K to reproduce dihydroquinone
dihyroquinone (active vit K) is necessary for __ of __
dihyroquinone (active vit K) is necessary for gamma-carboxylation of amino acids
should we use warfarin to completely block the vit K cycle?
NO, coagulation is necessary
what intake shouldn’t change while taking warfarin?
vit K
doctor should advise
we still need a bit
if they increase intake, dosage of Warfarin may need to be upped
consuming __ overrides the effects of warfarin
consuming vit K overrides the effects of warfarin
vitamin K cycle
- vit K epoxide –> vit K quinone (VKOR)
- vit K quinone –> dihydroquinone (VKOR, NAPH –> NADP+)
- dihydroquinone –> vit K epoxide (gamma-glutamyl carboxylase, CO2, O2, glutamic acid)
vit K biological functions
- blood clotthing
- bone metabolism
- other: tissue regen, cell cycle arrest, neuroprotection
vit K is a cofactor for __ carboxylation of glutamic acid residues
vit K is a cofactor for post-translational carboxylation of glutamic acid residues
vit K dependent gamma-glutamyl carboxylase
glutamic acid residues of Prothrombin and Osteocalcin are targeted
Prothrombin is a __ protein
coagulation protein
absence of gamma-carboxylation of glutamic acid residues impairs __ and leads to __ or __
absence of gamma-carboxylation of glutamic acid residues impairs coagulation/anticoagulation and leads to bleeding or thrombosis
7 blood clotting protein are made in the __, and organ responsible for metabolizing vit __
7 blood clotting protein are made in the liver, and organ responsible for metabolizing vit K
Gla =
gamma-carboxylated glutamic acid
each clotting factor has 10-12 __
each clotting factor has 10-12 Gla
Gla in clotting factors allows __ dependent association of clotting factors with phospholipids at site of injury
Gla in clotting factors allows Ca2+ dependent association of clotting factors with phospholipids at site of injury
proteins lacking Gla can’t __ with membrane or form __
proteins lacking Gla can’t associate with membrane or form clots
intrinsic blood coagulation pathway start when there is
injury to collagen
which coagulation factors are vit K dependent
2
7
9
10
vit K is necessary for __ of coagulation factors 2, 7, 9, 10
vit K is necessary for gamma-carboxylation of coagulation factors 2, 7, 9, 10
intrinsic blood coagulation process
- injured collagen activates factor 12
- factor 12 activates factor 11
- factor 11 activates factor 9
- factor 9 activates factor 10
- factor 10 converts prothrombin into thrombin
- thrombin converts fibrinogen to fibrin
extrnisic blood coagulation pathway starts with
vascular tissue trauma or injured tissue
extrinsic blood coagulation process
- injured tissue activates thromboplastin, which activates factor 7
- factor 7 activates factor 10
- factor 10 converts prothrombin into thrombin
- thrombin converts fibrinogen to fbrin
other K-dependent coagulation proteins
C, S, M, and Z
warfarin is a safe and effective oral __ if a therapeutic __ (__) is maintained
warfarin is a safe and effective oral anticoagulant if a therapeutic international normalized ratio (INR) is maintained
INR is affected by
diet
meds
illnesses
genetics
ppl with liver enzyme CYP2C9 cause liver to convert R-enantiomers to __-enantiomers which are 5x more potent __ of VKOR
ppl with liver enzyme CYP2C9 cause liver to convert R-enantiomers to S-enantiomers which are 5x more potent inhibitor of VKOR
3 problems when looking at role of dietary intake of vit K
- assessment of vit K status (use FFQ)
- bioavailability of vit K (highly variable)
- source (phylloquinone has much more rapid turnover than menaquinone)
__ contains a similar concentration of vit K as the liver
bone contains a similar concentration of vit K as the liver
osteocalcin = bone __ protein
osteocalcin = bone Gla protein
osteocalcin must be __ (requires vit K) to bind to __
osteocalcin must be gamma-carboxylation (requires vit K) to bind to Ca2+
increased osteocalcin = increased
increased osteocalcin = increased bone growth
nephrocalcin = kidney __ protein
nephrocalcin = kidney Gla protein
is vit K deficiency common
no
groups at risk for vit K deficiency
- Newborns have low vitamin K for the following reasons:
- Sterile gut — gut bacteria produce Menaquinone (K2)
- Breast milk is low in Vitamin K
- Chronic kidney disease
- Patients on antibiotics (sterile gut)
- Patients with liver disease
- Metabolism of Vitamin K is centralized in the liver
- Patients on anticoagulant therapy
- Fat malabsorption
- Bariatric surgery
why do newborns have low vit K
- sterile gut: gut bacteria produce menaquinone (K2)
- breast milk is low in vit K
solution to newborn vit K deficiency
IM injection of phylloquinone at birth
assessment of vit K levels
- plasma phylloquinone (doesn’t reflect stores)
- phylloquinone epoxide
- prothrombin time or plasma levels (only good when vit K is very low)
- measure non-gamma0carboxylated forms of thrombin and osteocalcin
