vitamin K Flashcards
1
Q
vitamin K aka
A
phylloquinone
2
Q
2 features of vit K
A
- napthoquinon nucleus = gives it biological function
- fatty acid side chain = cause lipid-soluble and drives vit K to membranes
3
Q
3 types of vit K
A
- phylloquinone
- menaquinones
- menadione
4
Q
phylloquinone
A
vit K1
found in plants
5
Q
menaquinones
A
vit K2
produced by bacteria
6
Q
menadione
A
synthetic vit K
7
Q
dietary source of vit K
A
dark leafy veg
8
Q
is vit K requirement altered in pregnancy?
A
NO
9
Q
2 locations of vit K absorption
A
- small intestine
- colon/lower digestive tract
10
Q
__ in lower digestive tract synthesize vit L
A
bacteria in lower digestive tract synthesize vit K
11
Q
vit K absorption rate in humans is __
A
vit K absorption rate in humans is highly variable
12
Q
vit K absorption requires __
A
vit K absorption requires lipids
13
Q
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
A
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
14
Q
2 methods of vit K absorption
A
passive diffusion
active transport
15
Q
main absorption of vit K
A
passive diffusion
16
Q
passive diffusion of vit K requires __ for emulsification, solubilization, and micelle formation
micelles __ into enterocyte
A
passive diffusion of vit K requires bile salts for emulsification, solubilization, and micelle formation
micelles passively diffuse into enterocyte
17
Q
what do we know about active transport of vit K
A
nothing really
18
Q
within enterocyte, vit K is put into
A
chylomicrons
19
Q
once vit K is in chylomicrons,
A
- chylomicron released into lymph
- LPL degrades lipoprotein, vit K delivered to extra-hepatic tissues
- vit K in chylomicron remnants reach liver
20
Q
vit K in liver
A
- liver stores some as menaquinone (bc it has slower turnover rate than phylloquinone)
- liver packs phylloquinone into VLDL, sends it to post-hepatic circulation
21
Q
vit K in liver
A
- liver stores some as menaquinone (bc it has slower turnover rate than phylloquinone)
- liver packs phylloquinone into VLDL, sends it to post-hepatic circulation
22
Q
why does the liver mainly store menaquinone
A
bc it has a slower turnover rate than phylloquinone
23
Q
circulation form of vit K
A
phylloquinone
24
Q
vit K in VLDL is
A
delivered to bone
25
where do we store vit K?
mostly in cell membrane of lung, kidneys, bone marrow
26
the liver __ vit K quickly, but __ very little
the liver **metabolizes** vit K quickly, but **retains** very little
27
excretion of vit K
1. phylloquinone is oxidized and conjugated with glucouronic acid for defecation (feces and bile)
some urine
28
spped of turnover of body's vit K pool
very fast
~1.5 days
29
all forms of vit K undergo __ __ to hydroquinone
all forms of vit K undergo **reversible** **reduction** to hydroquinone
30
biologically active vit K
hydroquinone
31
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
32
dietary form of vit K
vit K quinone (phylloquinone)
33
circulation form of vit K
vit K quinone
34
enzymes that use vit K as a cofactor
1. gamma-glutamyl carboxylase (biosynthesis of vit K-dependent clotting factors)
35
gamma-glutamyl-carboxylated protein binds __
gamma-glutamyl-carboxylated protein binds **Ca2+**
36
warfarin inhibits __
warfarin inhibits **vitamin K epoxide reductase (VKOR)**
37
at high doses, warfarin also inhibits __
at high doses, warfarin also inhibits **quinone reductases**
38
2 enzymes that warfarin inhibits
VKOR
quinone reductases
39
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**
40
dihyroquinone (active vit K) is necessary for __ of __
dihyroquinone (active vit K) is necessary for **gamma-carboxylation** of **amino acids**
41
should we use warfarin to completely block the vit K cycle?
NO, coagulation is necessary
42
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
43
consuming __ overrides the effects of warfarin
consuming **vit K** overrides the effects of warfarin
44
vitamin K cycle
1. vit K epoxide --> vit K quinone (VKOR)
2. vit K quinone --> dihydroquinone (VKOR, NAPH --> NADP+)
3. dihydroquinone --> vit K epoxide (gamma-glutamyl carboxylase, CO2, O2, glutamic acid)
45
vit K biological functions
1. blood clotthing
2. bone metabolism
3. other: tissue regen, cell cycle arrest, neuroprotection
46
vit K is a cofactor for __ carboxylation of glutamic acid residues
vit K is a cofactor for **post-translational** carboxylation of glutamic acid residues
47
vit K dependent gamma-glutamyl carboxylase
glutamic acid residues of Prothrombin and Osteocalcin are targeted
48
Prothrombin is a __ protein
**coagulation** protein
49
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**
50
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**
51
Gla =
gamma-carboxylated glutamic acid
52
each clotting factor has 10-12 __
each clotting factor has 10-12 **Gla**
53
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
54
proteins lacking Gla can't __ with membrane or form __
proteins lacking Gla can't **associate** with membrane or form **clots**
55
intrinsic blood coagulation pathway start when there is
injury to collagen
56
which coagulation factors are vit K dependent
2
7
9
10
57
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
58
intrinsic blood coagulation process
1. injured collagen activates factor 12
2. factor 12 activates factor 11
3. factor 11 activates factor 9
4. factor 9 activates factor 10
5. factor 10 converts prothrombin into thrombin
6. thrombin converts fibrinogen to fibrin
59
extrnisic blood coagulation pathway starts with
vascular tissue trauma or injured tissue
60
extrinsic blood coagulation process
1. injured tissue activates thromboplastin, which activates factor 7
2. factor 7 activates factor 10
3. factor 10 converts prothrombin into thrombin
4. thrombin converts fibrinogen to fbrin
61
other K-dependent coagulation proteins
C, S, M, and Z
62
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
63
INR is affected by
diet
meds
illnesses
genetics
64
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
65
3 problems when looking at role of dietary intake of vit K
1. assessment of vit K status (use FFQ)
2. bioavailability of vit K (highly variable)
3. source (phylloquinone has much more rapid turnover than menaquinone)
66
__ contains a similar concentration of vit K as the liver
**bone** contains a similar concentration of vit K as the liver
67
osteocalcin = bone __ protein
osteocalcin = bone **Gla** protein
68
osteocalcin must be __ (requires vit K) to bind to __
osteocalcin must be **gamma-carboxylation** (requires vit K) to bind to **Ca2+**
69
increased osteocalcin = increased
increased osteocalcin = increased **bone growth**
70
nephrocalcin = kidney __ protein
nephrocalcin = kidney **Gla** protein
71
is vit K deficiency common
no
72
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
73
why do newborns have low vit K
1. sterile gut: gut bacteria produce menaquinone (K2)
2. breast milk is low in vit K
74
solution to newborn vit K deficiency
IM injection of phylloquinone at birth
75
assessment of vit K levels
1. plasma phylloquinone (doesn't reflect stores)
2. phylloquinone epoxide
3. prothrombin time or plasma levels (only good when vit K is very low)
4. measure non-gamma0carboxylated forms of thrombin and osteocalcin
