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What is the difference between preformed and proformed Vitamin A?
Preformed is ACTIVE
Proformed is a precursor to vitamin A (in itself NOT useable)
What is another name for preformed Vitamin A? What is preformed Vitamin A stored as?
Retinol Esters (RE; retinol w/ FA attached)
Stored as Retinyl palmitate
What are sources of Preformed Vitamin A (Retinol esters)?
Animal products (dairy, liver, fish)
What are the three types of preformed Vitamin A and what is their difference in structure?
1) Retinol --> OH
2) Retinal --> Aldyhide
3) Retinoic acid --> Carboxylic acid
What is the name of the proformed Vitamin A's?
Carotenoids
What are the sources for Proformed Vitamin A (Carotenoid)?
Plant products (Orange, Yellow, Red colored!)
Proformed Vitamin A (Carotenoids) take ___x as much to equal preformed vitamin A (Retinol esters) activity.
12x
What example of Carotenoids is the orange pigment w/o oxygen? Which is the yellow pigment w/ oxygen?
Carotenes
Xanthophylls
What are the 2 types of Carotenes?
1) Carotene
2) Lycopene
What are the 3 types of Xanthophylls?
1) Cryptoxanthin
2) Lutein
3) Zeaxanthin
What are the 3 types of Retinol Esters (Preformed Vit A) and what are their functions?
1) Retinol -- Reproduction & Growth
2) Retinal -- Vision
3) Retinoic Acid -- Gene expression & Cell differentiation (fully oxidized, mainly used)
NOTE: RETINAl = Retina (vision); RetinOl = ReprOduction & GrOwth
What are the 2 functions of the carotenoids?
1) Anioxidant
2) Cell growth & differentiation
With the antioxidant function of carotenoids, they will quench ________, especially singlet oxygen and lipid peroxides.
ROS
Lutein and zeaxanthin (carotenoids) are concentrated where to prevent UV induced eye damage?
Macula
With the cell growth and differentiation function of carotenoids, they may _______ the growth and proliferation of several cancer lies, and supplements may ______ the risk of several cancers.
Inhibit
Increase
What are the 5 symptoms of a Vitamin A deficiency?
1) Night blindness (nyctalopia)
2) Xerosis (itching, burning of eyelid)
3) Xerophthalmia (dry eye from inadequate mucus production)
4) Bitot's spots (keratin deposition)
5) Permanent blindness
T/F: Hypervitaminosis A is due to proformed only
FALSE
Preformed only
What are 10 symptoms of Hypervitaminosis A?
1) Bone pain
2) Dry skin
3) Hair loss
4) Fatigue
5) Anorexia
6) Blurred vision
7) Headache
8) Liver damage
9) Portal hypertension
10) Ascites
Are Vitamin A supplements recommended? Why or why not?
NO
-- promotes oxidative damage, cell division, and destruction of other forms of Vit A
Vitamin A supplements can increase the risk of lung cancer, heart disease, and death in what population?
Smokers & former smokers
Is Vitamin A stable?
Retinol toxic, so usually tagged w/ FA to store (stored as Palmitate)
Does Vitamin A require digestion prior to absorption?
YES
NOTE: Vowels need to be digested before absorption (A/E); consonants do NOT (D/K)
What are the two steps for the digestion of Vitamin A?
1) Proteins & FA removed by digestive enzymes
2) Requires emulsification by bile salts to be absorbed as micelles
What is the bioavailability of Preformed Vitamin A? Proformed carotenoids? Does anything affect this absorption?
Preformed Vit A = 75-100
Carotenoids = 3-90% w/ cooking increasing absorption
How is Vitamin A absorbed? What percent is absorbed?
Passive diffusion in duodenum & jejunum
80% RE absorbed
What is the binding protein inside the cell that carries vitamin A? How about the one in the plasma?
Inside Cell = Cellular-RetinOl Binding Protein (CRBP)
Plasma = RetinAl binding protein
Retinol is reesterified to a retinol ester in the _________ by _________, transfering SN1 FA from its membrane bound structure onto retinol
Enterocyte
Lecithin (Retinol acyl transferase (LRAT))
T/F: Lecithin is the most abundant phospholipid in membranes
TRUE
Retinol esters are then incorporated into __________ & transported in the __________, where they will ultimately be stored (50-80%; 70%) in the __________.
Chylomicrons
Transported in lymphatic system
Liver (stellate cells)
How do chylomicrons release retinol into the hepatocyte?
Release a FA (hydrolase)
T/F: Free Retinoic acid is toxic, so it is bound
FALSE
Free retinol is toxic and must be bound (CRBP)
RBP-retinol is excreted by leaving the liver to circulate in the blood bound to what?
NOTE: RBP = Retinol binding protein
Thyroxine
What to cofactors are required to make RBP (Retinol binding protein)?
Protein & Zinc
What is the animal form of vitamin D we may consume?
Cholecalciferol (Vit D3) --> made from cholesterol
What is the plant form of Vitamin D we may consume?
Ergocalciferol (Vit D2)
Does Cholecalciferol (animal form) or Ergocalciferol (plant form) have a longer half-life?
Cholecalciferol = 15 days
Ergocalciferol = 13 days
What is the active form of vitamin D and is it made in the skin, liver, or kidneys?
Calcitriol (Kidneys)
What are the first 2 steps of Vitamin D synthesis that occur in the skin?
Step 1:
7-dehydrocholesterol --> Previtamin D3
Enzyme: UVB
Step 2:
Previtamin D3 --> Vitamin D3 (inactive) Calciferol
What is the third step of Vitamin D synthesis that occurs in the LIVER?
Vitamin D3 (inactive) Calciferol --> 25-hydroxyvitamin D3 (inactive; Calcidiol)
Enzyme = 25-hydroxylase
What is the fourth and final step of Vitamin D synthesis that occurs in the KIDNEYS?
25-hydroxyvitamin D3 (inactive; Calcidiol) --> 1,25-dihydroxyvitamin D3 (ACTIVE; Calcitriol)
Enzyme: 1alpha-hydroxylase
At what step does food sources of vitamin D enter the vitamin D synthesis?
Enters as Calciferol
25-hydroxylase and 1alpha-hydroxylase are both what type of enzyme?
Cytochrome P450 enzymes
To get the adequate amount of sunlight for Vitamin D synthesis, we should be getting ____-____ minutes between ___am-____pm, _____-____x per week?
5-10 mins
between 10am & 3pm
2-3x per week
What is the difference between the half life of the inactive Calcidiol (liver) and the active Calcitriol (kidney)?
Calcidiol = 2-3 weeks
Calcitriol = 4-6 hours
What are 8 factors that may affect our ability to synthesize & activate Vitamin D?
1) Season
2) Cloud cover
3) Latitude
4) Skin color
5) Sunscreen
6) Age
7) Malabsorptive conditions
8) Obesity
Is digestion necessary for Vitamin D before absorption? If so, what is done?
NO
How is Vitamin D absorbed? WHat percent is absorbed?
Part of micelles by passive diffusion
50% abosrbed
How is Vitamin D transported?
Part of lipoproteins (chylomicrons, VLDL) or Vitamin-D binding protein
Where is most of Vitamin D found? Where is most of it stored?
Found in BLOOD
Most stored in ADIPOSE; but tiny amount in muscle
What are 8 functions of Vitamin D?
1) Ca absorption & Phosphorus homeostasis
2) Gene expression (steroid hormone)
3) Cell growth, differentiation, and proliferation of WBC/stem cells
4) Increased absorption in SI
5) Increased renal reabsorption
6) Stimulate mobilization from trabecular bone
7) Muscle function/contractability (Ca concentration)
8) Immune system (nearly all immune cells contain vit D receptors)
What is the RDA for Vitamin D, from birth to death? (3)
0-12 months = 400 IU
1-70 years = 600 IU
>70 years = 800 IU
What type of Vitamin D deficiency demonstrates bowed legs and bilateral knee pain, and occurs more commonly in children?
Rickets
What type of Vitamin D deficiency demonstrates soft, spongy bones, muscle weakness, and bone pain and is seen more commonly in adults?
Osteomalacia
What is the best biomarker for Vitamin D?
25-hydroxyvitamin D (calcidiol)
NOTE: has the longest half life! (even though inactive)
Can Vitamin D become toxic? If so, does this occur w/ supplementation or dietary intake, or both?
YES (if exceeding daily doses of 10,000 IU for more than 6 months)
ONLY supplementation
What are 2 symptoms of Vitamin D toxicity?
1) Hypercalcemia & Hyperphosphatemia
2) Calcification of soft tissues (especially kidneys)
How do we regulate the amount of Vitamin D we activate?
Vitamin D response element (VDRE) which is located on DNA helps us to regulate gene expression
Who is the at risk populations for vitamin D deficiency and may need supplementation? (6)
1) Breastfed infants
2) Older adults
3) Limited sun exposure
4) More skin pigmentation
5) Fatty malabsorption (IBD, cystic fibrosis, celiac)
6) Obese patients or gastric bypass
Which patients should you NOT recommend vitamin D supplementation to?
Kidney, lung, and heart disease patients
What are the 8 best sources of Vitamin D?
1) Cod liver oil
2) Trout
3) Salmon
4) Mushrooms
5) Milk
6) Sardines
7) Soy, almond, oat milk derivatives
8) Ready-to-eat cereals
What is the type of Vitamin E we eat?
Alpha-tocopherol
NOTE: only structure recognized to meet human requirements
NOTE: tocotriol another form of Vit E
What are 7 sources of Vitamin E? What is the overall category these sources fall in to?
1) Wheat germ oil
2) Sunflower seeds
3) Almonds
4) Safflower oil
5) Hazelnuts
6) Peanuts
7) SOME spinach, broccoli, soybean oil, kiwi
Most fall under NUTS & SEEDS
(Vit E is the nuts and sEEds)
Is digestion required for Vitamin E? If so, what is done?
YES
-- remove esters using pancreatic esterase and duodenal mucosal esterase
How is vitamin E absorbed?
Part of micelles via passive diffusion
NOTE: this is same as all the other fat soluble vitamins
How is Vitamin E transported?
Lipoproteins
NOTE: same as all the other fat soluble vitamins
Where is Vitamin E stored?
Incorporated into the LIPID BILAYER of membranes
What are the 3 major functions of Vitamin E?
1) Antioxidant
2) Immune system
3) Inflammation and Platelets
What is the antioxidant function of Vit E? Where is this done?
Donates H to free radicals to protect PUFAs in plasma membrane
-- decreases risk of heart disease, cancer, macular degeneration
What is the immune system function of Vitamin E? (2)
Protein Kinase C inhibitor
Controls T cell function
What is the inflammation and platelet function of Vitamin E? (2)
Decreases production of enzymes that decrease arachidonic acid metabolism (phospholipase A2, LOX, COX)
Increase prostacyclin production (vasodilator and inhibitor of platelet aggregation)
What are the signs/symptoms of hypo or hypervitaminosis E? (5)
1) Hemolytic anemia (premies only)
2) Neuropathy (from disturbance in myelin production)
3) Retinopathy
4) Skeletal myopathy
5) Impaired immune response
How are natural structures of vitamin E different than synthetic structures/supplements?
Natural = ONLY biologically active isomers
Synthetic = FA attached (ester) and racemic mixture of isomers
Vitamin E works with _____ for antioxidant enzyme glutathione peroxidase?
Selenium (Se)
Higher fat intake requires ______ Vitamin E to protect form oxidation
MORE
Excess Vit E can ______ carotenoid and Vit K absorption, __________ the likelihood for bleeding
Inhibit
Increasing
What are the 3 vitamins that have antioxidant functions?
ACE
Vit A, Vit C, Vit E
What vitamin is the key to vitamin E regeneration?
(Vit) C is the key to (Vit) E regeneration
(C is the key to E)
What is the type of Vitamin K we eat, found in green plants? What is the type made by our bacteria in the LI?
Green plants = Phylloquinone (K1)
LI Bacteria = Menaquinone (K2)
How is Vitamin K absorbed? Transported?
Absorbed = Micelles by passive diffusion
Transported = Lipoproteins
NOTE: same as all the other fat-soluble vitamins!
Where is Phylloquinone (K1) stored?
Cell membranes of lungs, kidneys, bone marrow, pancreas, heart, brain, & adrenals
Where is Menaquinone (K2; MK-4) stored?
More concentrated in the kidneys & pancreas
What are the functions of Vitamin K?
1) Vitamin K-dependent carboxylases
2) Clotting & Bone formation!
With the vitamin K dependent carboxylases, it will add a carboxylic acid group to glutamate residues in specific proteins to make ___________ which are _____-binding sites found in clotting factors, prothrombin, and osteocalcin.
Carboxyglutamates
Calcium-binding sites
Where does most of our Vitamin K requirement come from?
Bacteria in LI
Who is at risk for Vit K deficiency? (3)
1) Newborns
2) Fat malabsorption disorders (CF, pancreatic CA, bile disorder)
3) Prolonged use of antibiotics
What are 2 symptoms of Vit K deficiency?
1) Increased bleeding
2) Poor bone growth
What is the TUL for Vitamin K?
NONE set
-- No toxicity symptoms form food or current supplmements
What are the food sources for Phylloquinones (K1)? (7)
1) Broccoli
2) Dark green leafy vegetables
3) Kiwi
4) Peas
5) Beans
6) Oils (canola, grapeseed, soybean, olive)
7) Margarine
(Plants!)
What are food sources for Menaquinones (K2)? (4)
1) Natto (fermented soybean)
2) Meat
3) Dairy
4) Eggs
(Animal products + fermented soybean (fermented like LI))