MODULE 1 Week 3: Vitamin D & K Flashcards
1
Q
** Which vitamin also functions as a (steroid) hormone?
A
D
2
Q
** Main functions of Vitamin D
A
- Hormone (chemical messenger)
- CALCIUM homeostasis/bone health
- Phosphorus homeostasis
- Cell differentiation, proliferation, growth
- Muscle tissue/strength/function
3
Q
** In what populations might vitamin D be considered CONDITIONALLY ESSENTIAL?
A
- elderly
- alcoholics
- People who live in the northeast
- People with kidney/liver issues
4
Q
** The DRI of vitamin D between age 9-69 is 600IU, how many cups of milk is that?
A
6
5
Q
** What 3 vitamins are involved in osteoporosis?
A
A, D, K
6
Q
** What is osteocalcin? Is is X dependent?
A
BONE gamma-carboxyglutamic acid-containing protein
Vitamin K dependent
7
Q
** What is gamma carboxylase?
A
Vitamin K dependent enzyme needed to CATALYZE GLA protein
8
Q
** Bioavailable form of vitamin D
A
1-25 OH (hydroxide)
9
Q
25(OH) v 1-25(OH) - where are each made?
A
25(OH)= liver
1-25(OH) = kidneys
10
Q
** Factors required for hydroxylation of vitamin D
A
- direct sunlight
- cholesterol
- good skin
- FUNCTIONAL LIVER & KIDNEYS
11
Q
** Are vitamin D receptors located on just the bone or elsewhere?
A
No, on EVERY organ of the body (basically)
12
Q
** What age group is most susceptible to vitamin D deficiency?
A
Elderly
13
Q
**Chron’s disease
A
Autoimmune GI disease - part of digestive tract becomes inflamed/ulcerated etc.
14
Q
** Vitamin D, T cells, autoimmunity
A
Vitamin D regulated hyper active immune response (autoimmune response) by regulating T cell activity in the body
15
Q
** What part of the intestine is the most vitamin D absorbed ?
A
Distal small intestine
16
Q
** Vitamin DBP is what?
A
Vitamin D binding protein
17
Q
What protein is vitamin D transported on ?
A
DBP (vitamin D binding protein)
18
Q
** Relationship with vitamin D and higher body fat
A
People with higher bod fat store more vitamin D in adipose tissues so requires higher vitamin D intake in order to achieve adequate SERUM vitamin D levels
19
Q
** Dietary vitamin D is absorbed through passive or active absorption
A
PASSIVE from micelles, incorporated in chylomicrons
20
Q
** Skin produced vitamin D is absorbed by passive or active?
A
Passive diffusion into blood
21
Q
** Cholecalciferol (is it active)?
A
D3; not active
22
Q
** Most abundant vitamin D form in BLOOD
A
25-OH (calcidiol)
23
Q
*** STEPS IN VITAMIN D METABOLISM/HYDROXYLATION
A
- Sunlight hits the skin and converts DEHYDROXYCHOLESTROL to D3(cholecalciferol)
- D3 is hydroxylated into 25(OH) in the LIVER
- (25(OH) secreted into the blood and transported on DBP)
- 25OH travels to KIDNEYS where it is converted to 1,25-OH
24
Q
** 1-25,OH is regulated by with hormone?
A
PTH (parathyroid)
25
** Most common test to assess vitamin D status? (What form is measured?)
25-OH blood test
26
** Calcidiol v calcitriol
Calcidiol = 25-OH
Calcitriol = 1,25-OH
27
** Non-genomic interactions of vitamin D involved (hint receptors)
Activation of vitamin D receptors in the cell membrane
28
** Genomic actions of vitamin D (calcitriol)
Bind to nuclear receptors and influence DNA sequences/protein transcription
29
** Vitamin D and serum calcium (eg. what happens with hypocalcemia)
1. Low blood calcium triggers release to PTH from parathyroid gland
2. ^ PTH causes more calcium to be reabsorbed (from kidneys) AND stimulates conversion to 25-OH to (ACTIVE) 1-25-OH
3. 1-25-OH travels to intestines to INCREASE Ca from the intestines/gut
30
** Vitamin D and phosphorus (hint related to calcium regulation)
- PTH released when sense low calcium
- Kidneys decrease excretion of Ca &(!) increase excretion of phosphorus & increase calcitriol 1-25-OH conversion
- 1-25-OH travels to INTESTINES where it increased absorption of Ca AND PHOSPHORUS
** PTH travels to bone to release Ca and Phosphorus from bone (to increase serum Ca)
31
** CELL PROLIFERATION VS. DIFFERENTIATION MEANS
P: Increase in the numbers of cells as a result of growth and division
D: process by which a cells changes from one type to another (usually to a more specialized cell)
32
** Vitamin D deficiency and psoriasis
Vitamin D involved in regulating cell differentiation/proliferation; people with psoriasis have an ACCELERATED rate in which new cells rise to the surface of the skin (causing the dry, skin scaling), which may be because they do not have enough vitamin D to regulate the rate of cell growth/rising
33
** Vitamin D and muscle (development and function)
Vit D facilitates normal muscle development and normal contraction/relaxation
34
** Does vitamin D promote slow and fast twitch muscle fiber development
FAST
35
** vitamin D and myopathy
Muscle weakness, increased falls
36
** Vitamin D and cardiovascular health, immune health, diabetes
C: helps regulate blood pressure and lipoprotein metabolism
I: Helps prevent autoimmunity (regulated hyper immune response) and helps mount defense against infection
D: Aids in pancreatic beta cell health and insulin function
37
** Does dietary or supplementation vitamin K need any digestion?
NO
38
** Symptoms of vitamin D deficiency (as related to muscles, calcium, LOOK UP
- Myopathy
- Calcium deposits
-
39
** What might occurs with too much vitamin D in the absence of vitamin K (hint vascular)
Calcium deposits - vascular calcification
40
** Menaquinone v Philoquinone
M: BACTERIAL vitamin K (K2)
P: DIETARY vitamin K (K1)
41
** What causes vitamin K deficiency in infants?
Born with STERILE intestines (can’t produce K2) so need bacteria from food/breast feeding etc.
42
** Can you get toxic amounts of vitamin D from sunlight?
No; excess hear on the skin prevents D3 from forming/reaching toxic levels
43
**** SYMPTOMS OF VIT D TOXICITY
- Anorexia
- Weight loss
- Renal dysfunction
- Irregular heart beat
- VASCULAR CALCIFICATION (happens in absence of vitamin K)
- Calcification of soft tissues
- Hypertension
44
** What is Rickets
A condition in infants of soft bones and skeletal deformities caused by failure of bone tissue to harden
45
**What is osteomalacia
A condition in adults of weak and softened bones that can be reversed with supplementation
46
**** SYMPTOMS VIT D DEFICIENCY
- osteomalacia
- rickets
- fatigue
- bone pain
- myopathy/muscle weakness/cramps
- depression
- infertility/reproductive issues
47
*** D2 v D3; which is more effective at raising blood Vit D levels?
D2 = ergocalciferol; made from PLANTS
D3= calciferol; made in human body
* D3 more effective at raising blood levels
48
** Non-fortified sources of D3 (calciferol)
- Flesh of fatty fish
- Fish liver oils
- eggs, cheese, beef liver (less so)
49
**Vitamin K absorption is facilitated by bile acid, pancreatic secretions, and X????
Presence of dietary fat
50
** Location of absorption of K2 V K3
K3 (dietary/supplemental) = Upper intestine (in micelles)
K2 (synthesized by bacteria) = Distal ileum/colon but VARIES by person
51
*** Blood transport of vitamin K occurs on/as part of what?
1. Chylomicrons
2. When reaches liver (as chylomicron remnant), liver incorporates vit K into VLDL and secrete back into blood (for circulation
52
** Vitamin K primarily stored in which part of cell? Is a large amount stored?
Cell membranes; no, only small amounts
53
*** PRIMARY function of vitamin K (hint enzyme activity of GLA)
Vitamin K necessary for post-translational carboxylation of GLA (glutamic acid enzyme) to form gamma-carboxylated GLA residue
**** Vitamin K is dependent for GLA (enzyme) to add CARBOXYL groups to peptides/proteins after synthesized in cell.
54
**** Vitamin K, GLA residues, Ca relationship
** Vitamin K needed for GLA enzyme to carboxylate peptides/proteins
** Carboxylated proteins (called residues) are able to bind CALCIUM, which is essential for many mechanisms
55
** While form of vitamin K does majority of vitamin come from in US diet?
Phylloquinone/K3 (from dietary sources)
56
** Is vitamin K inhibited by blood thinners?
Yes
57
*** 4 Coagulation/clotting factors that vitamin K synthesizes
2,7,9,10
58
** Warfarin (Coumadin): how does it interact with vitamin K to prevent clotting?
Warfarin inhibits the liver from processing substances into CLOTTING FACTORS (2,7,9,10) that are needed to clot blood
59
** T/F warfarin inhibits the activity of epoxied reductase?
T
60
** T/F vitamin D is derived from a steroid?
T
61
** Foods often fortified with vitamin D (both 2&3)
- diary products (milk, yogurt, cheese etc.)
- yogurt
- breads
- breakfast cereals
62
** What is 7-dehydrocholesterol?
Steroid (derived from cholesterol) that is in SKIN that is involved in absorbing UV rays into the skin (to form vitamin D)
63
** What affects cutaneous production of vitamin D (eg. environmental factors)
- time of day
- season
- latitude
- altitude
- air pollution etc.
64
*** Melanin and vitamin D
Melanin blocks UVB rays so people with dark skin need MORE time in the sun to generate enough vitamin D
65
** What % of dietary vit D is absorbed ?
50
66
** Does vitamin D require any digestion?
No
67
** What part of intestines is largest amount of vitamin D absorbed?
Jejunum
68
** T/F after absorption, DIETARY vitamin D is transported in chylomicrons?
T
69
** How is CUTANEOUS vitamin D transported in the blood? (Hint what protein?)
DBP (vitamin D binding protein)
70
** Where is calcidiol/25-OH cholecalciferol synthesized?
The LIVER
71
** Major “storage site” of vitamin D (as 25-OH) (hint: not an organ)
The BLOOD
72
** Where is 1-25-OH synthesized?
the KIDNEYS
73
** What 2 hormones regulated the RENAL synthesis of 1,25-OH?
PTH (in response to low Ca & Mg) and fibroblast-like growth factors (FGF)
74
** Does DBP bind tighter to 25-OH or 1-25,OH?
25-OH
75
** Genomic v Non-genomic (meaning)
Genomic = actions mediated through DIRECT DNA BINDING or transcription factor inactivation
Non-Genomic = actions mediated by membrane-receptors/interactions with CELL MEMBRANE
76
** Non-genomic actions of vitamin D (primarily related to what mineral?)
Binds to various membrane/intramembrane receptors to causing signals to be transmitted into the cell (signal transduction) that influence various cell functions
**help mediate calcium uptake/calcium concentration etc.
77
** Genomic functions of vitamin D (mechanisms of actions; VDR etc.)
Vitamin D can also enter the NUCLEUS and bind to VDR (vitamin D nuclear receptors) which causes changes to the receptor and therefore affecting GENE TRANSCRIPTION (protein making)
78
** Direct genomic action of calcitriol (VDR —> VDRE/transcription etc)
1. Calcitriol enters the nucleus and binds to NUCLEAR VDR,
2. Binding influences certain DNA sequences called VDRE (vitamin D response elements) which CHANGES GENE TRANSCRIPTION
3. RESULT = CHANGES IN PROTEIN SYNTHESIS
79
** Calcitriol synthesis stimulated my low X ?
CALCIUM
80
** Calcitriol and calcium (does one increase or decrease the other?)
Calcitriol INCREASED serum calcium levels
81
** Calcitriol and kidneys (hint calcium)
Calcitriol tells kidneys to reabsorb (not excrete) calcium in response to low Ca levels
82
** Calcitriol and intestines (hint calcium)
Calcitriol (in response to low calcium) travels to intestines (bound to DBP) and binds to VDRs to upregulate genes involved in calcium uptake
AKA calcitriol tells intestines to absorb MORE calcium
83
** PTH, calcitriol, and bone relationship (hint: RANKL)
Hypocalcemia stimulates PTH with stimulates conversion of calcitriol (1,25-OH)
1,25-OH travels to kidneys to and stimulates cytokines RANKL to stimulate osteoCLASTS that break down bone and release Ca from bone in order to raise serum calcium levels
84
** RANK/RANKL/Osteoprogerin system
In response to HYPOCALCEMIA
1. Calcitriol travels to bone
2. Calcitriol induces production of RANKL (cytokine) within OSTEOBLASTS (bone builder)
3. RANKL released from osteoblasts and bind to RANK (protein RECEPTOR) located on immature OSTEOCLASTS (bone break downers)
4. This binding stimulates release of substances that break down bone matrix (HCL) and release CALCIUM into the blood
5. Osteoprogerin acts to prevent excessive osteoclastogenesis (excessive bone break down/resorption)
85
** When RANKL is upregulated, Osteoprogerin is....?
Downregulated
86
** What does Osteoprogerin (OPG) do? How is RANKL involved?
Prevents excessive bone breakdown/resorption by BINDING TO RANKL (so RANKL can’t bind to RANK)
87
** Calcitriol and cell differentiation (adequate calcitirol is required for stem cells to differentiate into....?
Macrophages, monocytes (that becomes mature osteoclasts)
88
** Calcitriol and muscles (myopathy)
Deficiency associated with weak muscles, pain, fails, difficulty walking up stairs
** Involved in fast twitch muscle function and proper contraction and relaxation
89
** Vitamin D and cancer (hint: what does it do to cells? What does it prevent?)
Promotes cells differentiation and inhibits proliferation
Promotes apoptosis
90
*** Vitamin D and autoimmunity (hint: what does it do to immune system?)
Vitamin D deficiency associated with autoimmune conditions
MECHANISM: Vit D unregulate anti-inflammatory cytokines, immune-modulating (decreased hyper active immune activity) = T-cell differentiation!
91
*Vitamin D excreted through what substance in the feces
BILE
92
** Best plant source for vitamin D2
Mushrooms
93
** D3 is formed when steroid XXX in skin is broken down by sun
7-dehydrocholesterol
94
** Osteocalcin (bone gamma-carboxyglutamic acid-containing protein) & low vitamin K
low vitamin D = uncarboxylated osteocalcin
95
** Growth arrest specific gene 6 + vitamin K
Gas6 vitamin K dependent; needed for cell regulation/growth
96
** K2 is the traffic cop for ?
Calcium ; direct calcium to proper place it needs to be
97
** Vitamin K2 activates proteins that direct XXX to the proper destination
CALCIUM
98
** WHAT IS OSTEOCALCIN; is a marker of osteoXXX activity
Bone GLA protein
Marker of osteoBLAST activity
99
** Matrix GLA protein is strongest inhibitor of tissue calcification T/F? ** Proteins must be carboxylated by XXX to be physiologically active?
T
K2
100
**Why is supplementing with JUST calcium not effective in reversing bone loss (role of osteocalcin/matrix GLA protein)
Because without enough K2, calcium will not be directed to the correct location (the bones) which could result in bone loss and tissue calcification
K2 helps drive calcium/vitamin D into the bone by ACTIVATED/CARBOXYLATING osteocalcin (matrix GLA protein) that inhibits calcium into wrong places (soft tissue)
101
** Largest source of K2 in the western diet is?
Fatty cuts of ruminant animals/ruminant animals that are GRASS FED
102
** 2 main reasons Americans lack K2 in their diet
- emphasis on LOW FAT DIETS (because is fat-soluble vitamin)
- Factory feed lot system (not consuming grass which they convert to K2)
103
** Theory about increased heart attacks in winter
Because animals are feeding on less grass in winter (than summer) so humans are getting less K2, which contributes to ARTERIAL CALCIFICATION
104
** Dietary sources of vitamin K provided as phylloquinone or menaquinoine?
Phylloquinone
105
** Is bacterial synthesis of vitamin K enough to meet body’s needs?
No
106
** Is phylloquinone or menaquinone in higher concentrations in the liver?
MENAQUINONE (MK-4)
107
** In order for blood to clot, fibrinogen must be converted to X?
FIBRIN
108
Intrinsic v extrinsic pathways (collagen v tissue)
Intrinsic pathway is activated with collagen damage
Extrinsic pathway activated with tissue damage
109
FIBRINOGEN TO FIBRIN (substances involved in cascade eg. Prothrombin)
1. Prothrombin —> thrombin
2. Thrombin —> fibrinogen
3. fibrinogen —> FIBRIN
110
Prothrombin (clotting factor 2) is Vitamin K Xx?
DEPENDENT
111
*** All glutamic acid residues must be XXX by vitamin K in order for the protein to function
CARBOXYLATED
112
** Is vitamin K in its reduced/oxidized form when it’s involved in the carboxylation process?
REDUCED
113
*** Ingestion of diets high in vit K affect the effect of warfarin/Coumadin how??
OVERRIDE EFFECTS of warfarin
114
*** Would you need to increase or decrease the amount of warfarin in a client who is taking the medication and eats lots of green leafy vegetables?
INCREASE amount if eat a lot of leafy veggies
115
** Severe vitamin K deficiency associated with what disorders?
- Bleeding disorder/ “vitamin K deficiency bleeding/VKDB”
116
** Vitamin D deficiency looks like?
- low BMD
- increased fracture rates
- Cardiovascular disease
- ARTERIAL CALCIFICATION, inflammation
117
** Vitamin K toxicity looks like?
No toxicity established (synthetic form causes liver damage)
118
*** Populations where we are likely to see deficiency & why?
Infants = sterile intestines (no bacteria), breast milk LOW if vitamin K, low stores
Elderly = Consume small amounts
Chronic antibiotic users = kill bacteria necessary of K2 synthesis
People with fat malabsorption disorders = fat-soluble so needs dietary fat to be absorbed and these people can’t absorb
119
** Which 2 vitamins inhibits vitamin K?
A & E
120
**How to test for vitamin K (single test or not)?
No single biomarker; need to use:
- clotting time
- Prothrombin time
- measure % of under Carboxylated K-dependent proteins (osteocalcin, prothrombin etc.)
