Fat Soluble Vitamins Flashcards Preview

Gastrointestinal System > Fat Soluble Vitamins > Flashcards

Flashcards in Fat Soluble Vitamins Deck (32):
1

general properties of fat soluble vitamins

vitamins A, D, E, K

  • require an emulsifier: bile or other fats
  • more diverse fx than Bs ("energy metabolism")
  • excess stored in liver and adipose tissue
    • stores can last months-yrs
  • not easily excreted
    • higher toxicity risk

2

emulsifier

main example: bile

has hydrophilic head and hydrophobic tail to be in phase with GI secretions and fat-soluble vitamins

3

digestion and absorption of fat-soluble vitamins

  1. stomach: vitamins bound to proteins when we eat them. proteins are degraded in stomach, vitamins are released
  2. jejunum: fat-sol vitamins for micelles with bile salts, are passively transported into intestinal enterocytes
  3. intestinal enterocytes: packaged into chylomicrons and released into lymphatic system
  4. lymphatic system: chylomicrons trael up thoracic duct and empty into L subclavian v to enter circulation

4

vitamin A

  • sources
  • forms

retinyl esters (animal foods: liver) ⇔ beta-carotene (plant foods: carrots, sweet potato)

  • conversion between these two forms is reversible
  • conversion from retinol to retinoic acid is irreversible

forms

  • retinol - alcohol
  • retinal - aldehyde
  • retinoic acid - carboxylate group
  • beta-carotene - two retinals joined at tail
    • sometimes cleavage happens at wrong carbon, so you don't get the 2 vit A molecules expected
    • absorption of beta-carotene less effective than vit A

5

vitamin A: absorption, transportation, excretion

absorption

  • packaged in chylomicrons (as retinyl ester), transported to liver (converted to retinol in hepatocytes)
  • moved to stellate cells for storage
    • located in space of Disse between sinusoidal endothelial cells and heptatic epithelial cells (5-8% of liver cells)
    • in healthy liver, largest reservoir of vit A in body

transport

  • transported as retinoids (bound to retinol-binding protein)

excretion

  • small amounts excreted in urine

6

vitamin A functions

main fx

  • vision
  • maintenance of cornea, epithelial cells, mucous membranes, skin
  • important lipid-soluble antioxidant

diff forms, diff fx

  • retinol
    • ​supports reproductin
    • major transport and storage form
  • retinal
    • role in vision
  • retinoic acid
    • regulates transcription for cell diff, growth, embryonic devpt
  • beta-carotene
    • ​antioxidant

7

retinoic acid as a transcription factor

retinoic acid and vit D are unique in fx as transcription factors

RA-mediated transcription

  1. RA/retinoid binds to ligand-binding site
  2. receptor dimerization (heterodimer formation = RAR:RXR)
  3. DNA binding (RA response elements bind heterodimers)
  4. chromatin remodeling and recruitment of transc machinery to effect transcriptional modulation

8

vitamin A and mucous membranes

protects mucous membranes lining mouth, stomach, intestines, bladder, uterus, urethra, etc by promoting differentiation of epithelial cells and goblet cells

 

in absence of vitamin A, goblet cells can't fx properly = flattened/abnormal epi cells

9

pharmacological uses of vitamin A

  • retinoic acid
    • treatment of acute promyelocytic anemia
  • All Trans Retinoic Acid (ATRA) (tretinoin)
    • RetinA: topical cream tx for acne, age spots
  • 13-cis retinoic acid (isotretinoin)
    • Accutane: oral tx for severe acne but also TERATOGENIC ⇒ requires use of effective contraception

10

vitamin A and vision

retinal

maintains cornea, aids in conversion of light energy to nerve impulses

  • rod cells in retina contain rhodopsin (opsin + retinal)
    • critical for night vision/B&W vision
  • light + rhodopsin = conversion of retinal from cis to trans, which releases it from opsin
    • opsin initiates signal transduction cascade to nerve cells that communicate with visual center
  • trans retinal is converted back to cis; rhodopsin is reformed

takeaway: vitamin A critical for night vision

11

vitamin A deficiency

  • might occur through...
    • inadequate intake (primary def)
    • poor absorption of fats - CF, Crohn's disease, liver disease, high alcohol intake (secondary def)
  • vit A status depends on other factors
    • stores in liver
    • ability to make retinol binding proteins (for transport)
  • see symptoms in eyes, epithelial tissue, immune fx

 

12

vit A defiency symptoms

EYES

  • night blindness (inadequate retinal  in retina)
  • progression to blindness (xerophthalmia)
    • inadequate vit A at cornea
  • stages
    • xerosis: corneal drying
    • Bitot spots: triangular gray spots on eye (keratin buildup on conjunctiva)
    • keratomalacia: softening of cornea
    • xerophthalmia: corneal degen and blindness

EPITHELIAL CELLS

  • keratinization/hyperkeratosis: affects skin, GI tract, resp tract, urinary tract epi cells
    • change in size/shape
    • dry, rough, scaly skin
    • abnormal digestion/absorption in GI
    • weakened defenses in resp tract, vagina, inner ear, urinary tract

IMMUNE SYSTEM

  • impaired immunity (prone to infection diseases)

13

vit A toxicity

risk factors include...

  • frequent consumption of liver
  • systemic use of retinoic acid analogues
    • birth defects: cranofacial malformations, CNS/thymus/heart issues

**beta-carotene: no tox!

 

14

beta-carotene excess

beta-carotene is not efficiently converted; excess is stored in the fat under skin

NOT HARMFUL

symptoms: yellowing of skin due to accumulation

15

vitamin D

  • name
  • why it's called "conditional"/a "prohormone"
  • how it's made

calciferol

 

body can synthesize it from cholesterol with UV light given exposure to sun for 10-15min x 2-3 times/wk

16

vitamin D synthesis

  • on sunlight exposure:

pro-vitamin D3 (7-dehydrochol) → pre-vitamin D3

  • vitamin D3 (either pre-D3 that's isomerized or ingested D3) binds to DBP (vit D binding protein) in bloodstream, and is transported to liver

 

  • in liver: hydroxylation[enzyme: liver 25-hydroxylase]

D3 → 25-hydroxycholecalciferol

  • in kidney: hydroxylation [enzyme: 25-hydroxyvitamin D3-1-OHase]

25-hydroxycholecalciferol → active 1,25(OH)2D3 (calcitriol)

 

17

vitamin D sources

diff types of fish, fortified milk, mushrooms

 

18

vitamin D functions

  • Ca, PO4 homeostasis
    • increases Ca absorption (sm intestines)
    • helps release Ca from bone (if req)
  • bone health
  • immune fx
  • reduction of inflammation and apoptosis
  • bp regulation
  • regulation of gene expression [prohormone]
    • binds to VDR (vit D receptor) and interacts with target gene promoters

19

vitamin D deficiency risk factors

  • dark skin (pigment reduced vitD synth)
  • limited sun exposure 
  • elderly (lose ability to activate D)
  • people with little or no [fortified] milk in diet (vegans, lactose-intolerant) or breastfeeding moms who aren't supplementing

can lead to rickets and osteomalacia

20

rickets

vitamin D deficiency

  • most children (worldwide; rare in US - breastfed black babies with poor vitD intake, reduced ability to synth)
  • symptoms
    • inadequate calcification of bones
      • growth retardation, skeletal abnormalities (bowed legs)
    • lax muscles (protruding abd) and muscle spasms
    • beaded ribs (poor bone/cartilage interface)
    • delayed closure of fontanels: rapid head enlargement

21

osteomalacia/osteoporosis

vitamin D deficiency : poor mineralization leading to soft, brittle, deformed bones

  • affects adults
  • causes
    • long-term usage of anticonvulsants (phenobarbital, phenytoin): increased breakdown of vit D in liver
    • chronic kidney disease: low production of calcitriol
  • symptoms
    • soft, brittle, deformed bones
    • ​progressive weakness
    • pain in pelvis, lower back, legs

22

vitamin D toxicity

most likely of the vitamins to have toxic effects when consumed in excess!!!

NOT FROM SUNLIGHT/DIETARY SOURCES - supplementation only

  • excess vit D leads to increased blood Ca
    • precipitate in soft tissues (blood vessels, kidney, heart, lungs) - can cause death

23

vitamin E

aka tocopherol

tocopherol is actually a general term for 8 related compounds (4 tocopherols, 4 tocotrienols) of which one has vitamin E activity...

D-ISOMER OF ALPHA TOCOPHEROL

*found in nuts/oils - easily destroyed by oxygen and heat [ex. frying]

24

vitamin E functions

  • most effective lipid-soluble antioxidant
    • protects polyunsat FAs in cell membranes from peroxidation
  • prevents platelet aggregation and monocyte adhesion
  • helps maintain fertility

25

vitamin E: antioxidant activity & regeneration

  • ROS accumulate in body, wreak havoc
    • mitochondrial ETC generates majority (superoxide, hydrogen peroxide)
    • sequential reduction of oxygen (superoxide anion, peroxide, hydroxyl radical)
  • ROS target cellular membranes' unsaturated FAs via lipid peroxidation
    • vitamin E donates H to lipid radicals to protect membrane integrity
  • active vitamin E is regenerated by vitamin C
    • vit E is dependent on vit C for activity

26

vit E deficiency

  • primary deficiency is rare (can occur in premature infants)
    • preterm infants given supplemental vitamin E!
  • can occur due to fat malabsorption (CF, pancreatic insufficiency)
  • symptoms
    • erythrocyte hemolysis due to oxidation of polyunsat FAs
    • leads to ​hemolytic anemia

27

vit E toxicity

non-toxic except in HUGE doses

hard to develop from food; might be able to develop with huge exogenous supplemental doses

  • excess vit E interferes with vitamin K's role in blood clotting (risk of hemorrhage)
  • can lead to nerve damage

28

vitamin K

  • menaquinones (animal source) - synthesized by gut bacteria
  • phylloquinones (plant form) - green leafy feg, broccoli, peas, green beans, oils

29

vitamin K function

  • required cofactor for post-translational carboxylation of Glu

Glu → gamma-carboxylglutamate (Gla)

  • rxn catalyzed by gamma-glutamyl carboxylase
  • product (Gla) has key roles in blood clotting and bone mineralization (osteocalcin)
    • involved in both intrinsic and extrinsic pathways of clotting

vitamin K dependent proteins (VKD proteins) require several Gla residues (9-13) for normal fx

30

vitamin K deficiency

  • newborns have low stores
    • receive vit K dose at birth due to sterile intestinal tract, lack of gut bacteria to make it!
  • secondary deficiency can occur due to antibiotics or malabsorption
  • symptoms
    • hemorrhage
    • bruisability
    • mucosal bleeding

31

vitamin K toxicity

no toxicity known, BUT pts taking warfarin/coumadin should be careful eating vitamin K rich foods

  • warfarin works by decreasing vit K activity, lengthening clotting time

32

interrelationships of fat-soluble vitamins

  • vitamin E protects vitamin A from oxidation
  • vitamin C protects vitamin E from oxidation
  • vitamins A, D, K all play roles in bone growth/remodeling