Fat Soluble Vitamins

Question 1

natural form of vit A

Answer 1

retinol

Question 2

what do the retinoids include

Answer 2

1. retinol: storage form of Vit A, found in animal tissues. is a primary alcohol
2. retinal: aldehyde derivative of retinol when oxidised
3. retinoic acid: acid derived from oxidation of retinal. cannot be produced in body
4. beta-carotene: plant foods contain it.
   - AKA provitamin A.
   - oxidatively cleaved in intestine to give 2 retinal molecules.
   - has antioxidant activity

Question 3

sources of vitamin A

Answer 3

• liver
• kidney
• cream
• butter
• egg yolk
• yellow, orange, daark green vegertables and fruits good sources of carotenes

Question 4

vit A absorption and transport to liver

Answer 4

• retinyl esters -> retinol and FFA
• b-carotene -> retinal -> reduced to retinol
• both these retinols re-esterified in enterocytes using fatty CoA
• secreted as component of chylomicrons in lymphatic system.
• chylomicron remnants containing retinyl esters taken up by and stored in liver

Question 5

release from liver

Answer 5

• retinol binding protein complexed with transthyretin transports retinol through blood
• binds to transp protein on surface of peripheral tissue cells, allows retinol to enter

Question 6

retinoic acid mechanism of action

Answer 6

• retinol oxidised to retinoic acid
• binds to receptor acid receptors RAR in nucleus
• retinoic acid-RAR complex binds to response elements on DNA and regulates RNA synthesis
• allows control of specific protein eg keratin

Question 7

functions of vit A

Answer 7

• vision maintenance (retinoic acid not involved)
• epithelial cell maintenance - differentiation - mucus secretion - immune syst
• reproduction; supports spermatogenesis and prevents fetal resorption in females (retinoic acid not involved)
• bone growth

Question 8

describe visual cycle vit A

Answer 8

• 11-cis retinal + opsin -> rhodopsin
• light + rhodopsin -> all-trans retinal + opsin
• all-trans retinal -> all trans retinol -> all-trans retinyl esters -> 11-cis retinol -> 11-cis retinal

Question 9

effects of vit A deficiency

Answer 9

• earliest sign: nyctalopia (night blindness)
• prolonged deficiency = permanent loss of visual cells
• severe deficiency xerophthalmia ; untreated = blindness

Question 10

what is xerophalthamia

Answer 10

• pathologic dryness of conjunctiva and cornea caused in part by inc keratin synthesis
• untreated -> corneal ulceration -> blindness due to formation of opaque scar tissue

Question 11

which vit A is used to treat mild acne + skin aging

Answer 11

all-trans retinoic acid (tretinoin) oral too toxic

Question 12

what is oral tretinoin used for

Answer 12

acute promyelocytic leukemia

Question 13

what is isotretinoin used for

Answer 13

• severe cystic acne.
• is teratogenic, should be avoided in women of child-bearing capacity

Question 14

how is psoriasis treated

Answer 14

oral synthetic retinoid

Question 15

excess of vitamin A

Answer 15

• hypervitaminosis A
• skin dry and pruritic ( decreased keratin)
• liver enlarged - can become cirrhotic
• CNS-> rise in intracranial pressure can mimic symptoms of brain tumour.
• decreased bone mineral density + increased risk of fractures
• teratogenesis in pregnant women

Question 16

which retinoid functions as a hormone

Answer 16

retinol

Question 17

active form of vitamin E

Answer 17

alpha-tocopherol

Question 18

function of vit E

Answer 18

• antioxidant in prevention of nonenzymic oxidations, eg oxidation of LDL and peroxidation of polyunsaturated FA

Question 19

effect of vit C on vit E

Answer 19

C regenerates active vit E

Question 20

sources of vit E

Answer 20

• vegetable oils rich source
• liver and eggs moderate source

Question 21

vit E deficiency

Answer 21

• newborns can obtain from breast milk/supplements to prevent haemolysis and retinopathy
• in adults, usually due to defective lipid absorption/transport
• abetalipoproteinemia caused by defecr in formation of chylomicrons result in vit E deficiency

Question 22

what is the least toxic fat sol vitamin

Answer 22

vit E

Question 23

active molecule of vitamin D

Answer 23

• calcitriol

Question 24

vit D distribution

Answer 24

• collagen synthesis intermediate converted to vit D3 in dermis + epidermis when exposed to sunlight, transp to liver by vit d-binding protein
• diet; vit d2 found in plants and vit d3 found in animal tissues. dietary vit D packaged into chylomicrons

Question 25

how is vit d formed

Answer 25

- vit d2 + d3 converted to calcitriol by 2 sequential hydroxylation reactions - 1st in liver forms calcidiol - 2nd in kidneys form calcitriol

Question 26

functions of vit D

Answer 26

- maintain adequate ca2+ serum levels - inc ca2+ mobilisation from bone - inc renal resorption ca2+ - dec renal excretion of ca2+ - inc intestinal absorption of ca2+

Question 27

how does vit d increase intestinal absorption of calcium

Answer 27

- calcitriol binds to cytosolic receptor in intestinal cell and interacts w/ response elements on DNA - increases gene expression of calbindin

Question 28

sources of vit D

Answer 28

- fatty fish - liver - egg yolk

Question 29

Vit D deficiency

Answer 29

diet causes: - rickets in children - continual formation of collagen matrix but not mineralisation - soft and pliable bones - osteomalacia in adults - demineralisation of bones increases susceptibility to fracture -bow legs mutation in vit d receptor causes hereditary vit d-deficient rickets

Question 30

Renal osteodystrophy causes, effects and treatment

Answer 30

- caused by chronic kidney disease - decreased vit D formation, hyperphosphatemia and hypocalcemia - low ca2+ = increase in PTH -> associated bone demineralisation - treated with vit d supplementation + PO43- reduction therapy

Question 31

what is hypoparathyroidism + treatment

Answer 31

- lack of PTH causes hypocalcemia and hyperphosphatemia as PTH increases phosphate excretion - treated with vit D

Question 32

Vit D toxicity symptoms

Answer 32

- loss of appetite - nausea - thirst - weakness - hypercalcemia - ca2+ deposits in soft tissue (metastatic calcification) - excess vit d produced in skin is converted to inactive form so doesnt cause toxicity

Question 33

principal role of vit K

Answer 33

- coenzyme in carboxylation of glutamic acid residues to gamma-carboxyglutamate (Gla) in post-translational protein modification - req y-glutamylcarboxylase, O2, CO2, hydroquinone form of vit K (gets oxidised to epoxide form) - Gla residues also used to form osteocalcin + matrix Gla protein in bones

Question 34

active forms of vit K

Answer 34

- plants as phylloquinone (K1) - intestinal bacteria as menaquinone (K2) - menadione (synthetic form of vit K) can be converted to K2

Question 35

what can inhibit formation of Gla residues

Answer 35

warfarin - synthetic analog of vit K (inhibits VKOR, enzyme req to regenerate functional form hydroquinone form of vit K

Question 36

what blood clotting proteins is vit k involved in formation of

Answer 36

- prothrombin - FVII - FIX - FX

Question 37

vitamin K sources

Answer 37

- cabbage - kale - spinach - egg yolk - liver - intestinal bacteria

Question 38

vitamin K deficiency

Answer 38

- unusual as adequate amounts in diet and bacteria - decrease in bacterial gut population eg by antibiotics -> leads to hypoprothrombenima -> bleeding tendency therefore may need vit K supplementation cephalosporin antibiotics have warfarin-like mechanism, inhibits VKOR - deficiency can also affect bone health

Question 39

why can newborns have vit K deficiency

Answer 39

- sterile intestines + breastmilk provides only 1/5th of req amount - therefore single intramuscular dose as prophylaxis against haemorrhagic disease of the newborn

Question 40

Vit K excess

Answer 40

- prolonged admin of large doses of menadione can cause haemolytic anaemia and jaundice in infants due to RBC membrane damage