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IHN: Biochemistry 2 > vitamin K > Flashcards

vitamin K Flashcards

1
Q

vitamin K aka

A

phylloquinone

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2
Q

2 features of vit K

A
  1. napthoquinon nucleus = gives it biological function
  2. fatty acid side chain = cause lipid-soluble and drives vit K to membranes
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3
Q

3 types of vit K

A
  1. phylloquinone
  2. menaquinones
  3. menadione
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4
Q

phylloquinone

A

vit K1
found in plants

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5
Q

menaquinones

A

vit K2
produced by bacteria

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6
Q

menadione

A

synthetic vit K

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7
Q

dietary source of vit K

A

dark leafy veg

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8
Q

is vit K requirement altered in pregnancy?

A

NO

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9
Q

2 locations of vit K absorption

A
  1. small intestine
  2. colon/lower digestive tract
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10
Q

__ in lower digestive tract synthesize vit L

A

bacteria in lower digestive tract synthesize vit K

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11
Q

vit K absorption rate in humans is __

A

vit K absorption rate in humans is highly variable

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12
Q

vit K absorption requires __

A

vit K absorption requires lipids

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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

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14
Q

2 methods of vit K absorption

A

passive diffusion
active transport

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15
Q

main absorption of vit K

A

passive diffusion

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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

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17
Q

what do we know about active transport of vit K

A

nothing really

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18
Q

within enterocyte, vit K is put into

A

chylomicrons

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19
Q

once vit K is in chylomicrons,

A
  1. chylomicron released into lymph
  2. LPL degrades lipoprotein, vit K delivered to extra-hepatic tissues
  3. vit K in chylomicron remnants reach liver
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20
Q

vit K in liver

A
  1. liver stores some as menaquinone (bc it has slower turnover rate than phylloquinone)
  2. liver packs phylloquinone into VLDL, sends it to post-hepatic circulation
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21
Q

vit K in liver

A
  1. liver stores some as menaquinone (bc it has slower turnover rate than phylloquinone)
  2. liver packs phylloquinone into VLDL, sends it to post-hepatic circulation
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22
Q

why does the liver mainly store menaquinone

A

bc it has a slower turnover rate than phylloquinone

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23
Q

circulation form of vit K

A

phylloquinone

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24
Q

vit K in VLDL is

A

delivered to bone

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25
Q

where do we store vit K?

A

mostly in cell membrane of lung, kidneys, bone marrow

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26
Q

the liver __ vit K quickly, but __ very little

A

the liver metabolizes vit K quickly, but retains very little

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27
Q

excretion of vit K

A
  1. phylloquinone is oxidized and conjugated with glucouronic acid for defecation (feces and bile)

some urine

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28
Q

spped of turnover of body’s vit K pool

A

very fast
~1.5 days

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29
Q

all forms of vit K undergo __ __ to hydroquinone

A

all forms of vit K undergo reversible reduction to hydroquinone

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30
Q

biologically active vit K

A

hydroquinone

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31
Q

active form of vit K is __ after a vit K dependent rxn

A

active form of vit K is regenerated after a vit K dependent rxn

32
Q

dietary form of vit K

A

vit K quinone (phylloquinone)

33
Q

circulation form of vit K

A

vit K quinone

34
Q

enzymes that use vit K as a cofactor

A
  1. gamma-glutamyl carboxylase (biosynthesis of vit K-dependent clotting factors)
35
Q

gamma-glutamyl-carboxylated protein binds __

A

gamma-glutamyl-carboxylated protein binds Ca2+

36
Q

warfarin inhibits __

A

warfarin inhibits vitamin K epoxide reductase (VKOR)

37
Q

at high doses, warfarin also inhibits __

A

at high doses, warfarin also inhibits quinone reductases

38
Q

2 enzymes that warfarin inhibits

A

VKOR
quinone reductases

39
Q

when we stop inhibition caused by warfarin, we stop producing __ bc we block __ of vit K to reproduce __

A

when we stop inhibition caused by warfarin, we stop producing active vit K bc we block recycyling of vit K to reproduce dihydroquinone

40
Q

dihyroquinone (active vit K) is necessary for __ of __

A

dihyroquinone (active vit K) is necessary for gamma-carboxylation of amino acids

41
Q

should we use warfarin to completely block the vit K cycle?

A

NO, coagulation is necessary

42
Q

what intake shouldn’t change while taking warfarin?

A

vit K
doctor should advise
we still need a bit
if they increase intake, dosage of Warfarin may need to be upped

43
Q

consuming __ overrides the effects of warfarin

A

consuming vit K overrides the effects of warfarin

44
Q

vitamin K cycle

A
  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
Q

vit K biological functions

A
  1. blood clotthing
  2. bone metabolism
  3. other: tissue regen, cell cycle arrest, neuroprotection
46
Q

vit K is a cofactor for __ carboxylation of glutamic acid residues

A

vit K is a cofactor for post-translational carboxylation of glutamic acid residues

47
Q

vit K dependent gamma-glutamyl carboxylase

A

glutamic acid residues of Prothrombin and Osteocalcin are targeted

48
Q

Prothrombin is a __ protein

A

coagulation protein

49
Q

absence of gamma-carboxylation of glutamic acid residues impairs __ and leads to __ or __

A

absence of gamma-carboxylation of glutamic acid residues impairs coagulation/anticoagulation and leads to bleeding or thrombosis

50
Q

7 blood clotting protein are made in the __, and organ responsible for metabolizing vit __

A

7 blood clotting protein are made in the liver, and organ responsible for metabolizing vit K

51
Q

Gla =

A

gamma-carboxylated glutamic acid

52
Q

each clotting factor has 10-12 __

A

each clotting factor has 10-12 Gla

53
Q

Gla in clotting factors allows __ dependent association of clotting factors with phospholipids at site of injury

A

Gla in clotting factors allows Ca2+ dependent association of clotting factors with phospholipids at site of injury

54
Q

proteins lacking Gla can’t __ with membrane or form __

A

proteins lacking Gla can’t associate with membrane or form clots

55
Q

intrinsic blood coagulation pathway start when there is

A

injury to collagen

56
Q

which coagulation factors are vit K dependent

A

2
7
9
10

57
Q

vit K is necessary for __ of coagulation factors 2, 7, 9, 10

A

vit K is necessary for gamma-carboxylation of coagulation factors 2, 7, 9, 10

58
Q

intrinsic blood coagulation process

A
  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
Q

extrnisic blood coagulation pathway starts with

A

vascular tissue trauma or injured tissue

60
Q

extrinsic blood coagulation process

A
  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
Q

other K-dependent coagulation proteins

A

C, S, M, and Z

62
Q

warfarin is a safe and effective oral __ if a therapeutic __ (__) is maintained

A

warfarin is a safe and effective oral anticoagulant if a therapeutic international normalized ratio (INR) is maintained

63
Q

INR is affected by

A

diet
meds
illnesses
genetics

64
Q

ppl with liver enzyme CYP2C9 cause liver to convert R-enantiomers to __-enantiomers which are 5x more potent __ of VKOR

A

ppl with liver enzyme CYP2C9 cause liver to convert R-enantiomers to S-enantiomers which are 5x more potent inhibitor of VKOR

65
Q

3 problems when looking at role of dietary intake of vit K

A
  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
Q

__ contains a similar concentration of vit K as the liver

A

bone contains a similar concentration of vit K as the liver

67
Q

osteocalcin = bone __ protein

A

osteocalcin = bone Gla protein

68
Q

osteocalcin must be __ (requires vit K) to bind to __

A

osteocalcin must be gamma-carboxylation (requires vit K) to bind to Ca2+

69
Q

increased osteocalcin = increased

A

increased osteocalcin = increased bone growth

70
Q

nephrocalcin = kidney __ protein

A

nephrocalcin = kidney Gla protein

71
Q

is vit K deficiency common

A

no

72
Q

groups at risk for vit K deficiency

A
  • 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
Q

why do newborns have low vit K

A
  1. sterile gut: gut bacteria produce menaquinone (K2)
  2. breast milk is low in vit K
74
Q

solution to newborn vit K deficiency

A

IM injection of phylloquinone at birth

75
Q

assessment of vit K levels

A
  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

IHN: Biochemistry 2 (38 decks)

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