Week 6: Vitamin A, C, D, E and K

Question 1

Anything yellow and orange

Answer 1

β-carotene derived

Question 2

Vitamin A AKA

Answer 2

Retinol

Question 3

β-Carotene->

Answer 3

Retinal

Question 4

β-carotene structure

Answer 4

cut in half are 2 molecules of retinaldehyde

Question 5

Processing of β-carotene

Answer 5

β-carotene is carried by bile acids for absorption into intestinal enterocytes

β-carotene -> 2x Retinaldehyde –> Retinol (alcohol) + retinoic acid

Retinol is transported because aldehydes are very reactive

Don’t want retinoic acid because can reduce the pH of the blood (some retinoic acid is made from retinaldehyde)

Retinol + FA ester -packaged in a chylomicron-> carried by chylomicron -LPL processing (removing triglycerides)-> remnants primarily stored on hepatocyte but some are stored in stellate cell (stored as retinol)

When retinol is released from storage it is bound by RBP (Retinol binding protein) major protein that carries retinol because it is lipophilic

Retinol + RBP -> delivered to tissues that need it (extrahepatic cells -> depending on the tissue can be converted to retinaldehyde form or stored for a period of time in the Fatty-acyl form cna also be converted to retinoic acid (this is tissue-dependent

Question 6

What is the connection between β-carotene and bile acids?

Answer 6

Both are hydrophobic so β-carotene is carried by bile acids for absorption into intestinal enterocytes

Question 7

Retinol tissue-dependent uses

Answer 7

Retinol -> retinoic acid -> Retinoic acid which serves as a transcription factor

RAR (Retinoic Acid Receptor)

RXR (Retinoic X Receptor)

So retinoic acid binds to RAR and RXR which can now bind to the promoter (RARE Retinoic Acid Element) which generates protein and proliferation and differentiation genes)

• MMPS
• Proliferation-related genes
• Differentiation-related genes

Question 8

Retinol skin cream effects

Answer 8

increases the potential for the proliferation of skin cells

• enhances UV damage repair
• Reduce hyper-proliferation in Psoriasis
• Accelerate Wound healing

Question 9

Main functions of retinoic acid

Answer 9

• Drives gene expression cell proliferation and differentiation (ie skin cells)
• Role in vision: Retinol comes in and is converted to -> (cis-Retinaldehyde) binds to rhodopsin and G protein causes Trans configuration in retinaldehyde and get depolarization of cell and get a neural transmission for light vision

Question 10

Vitamin C AKA

Answer 10

Ascorbic Acid

Question 11

Functions of Vitamin C

Answer 11

Collagen cross-linking & lysine-hydroxylation

Will cause collagen crosslinking issues throughout the body but think Scurvy (Gums, lips and skin etc.) because these have a delicate basement membrane

Proline and lysine AAs in collagen, in order for the triple helix of collagen to form need a hydroxylation reaction and put hydroxyl groups on theses AAs (need this to happen for the triple helix to form

The crosslinking occurs via deaminated lysine residues creating aldehyde groups which crosslink and gives a strong tensile structure of collagen

If no vitamin C then the crosslinking and triple helix formation is compromised

So in the face of deficient triple helix formation and crosslinking then will have weak basement membrane structure leading to epithelial problems (ruptures, delayed wound healing) Scurvy

Also, works as an antioxidant (free radical scavenger)

• L-Ascorbic Acid <->-L-dihydroascorbic Acid
• Vitamin C is important as a flu remedy

Question 12

Primary collagen

Answer 12

Collagen IV

Question 13

Mechanism of scurvy

Answer 13

Vitamin C no collagen IV triple helix and crosslinking

Question 14

Sources of Vitamin D

Answer 14

7-dehydrocholesterol with UV rays -breaks cholesterol ring-> Vitamin D3

or

Dietary Vitamin D3

Question 15

Vitamin D3 processing

Answer 15

Vitamin D3 binds to vitamin D BP -transport-> liver

Vitamin D3 + Vitamin D BP in the liver -> Hydroxylation of 25th C

25(OH) D -transported to the kidney->

25(OH) D in the kidney -another hydroxylation on 1st C-> 1α25(Oh) D

The active form of Vitamin D = 1α25(Oh) D

Question 16

How to get active Vitamin D3

Answer 16

need sunlight or dietary D3

Question 17

25(Oh) D and PTH

Answer 17

The parathyroid hormone can stimulate the kidney and increase the expression and production of 1α25(Oh) D

Increases the active form 1α25(Oh) D by a decrease in plasma Ca2+

1α25(Oh) D and PTH are required for bone resorption (Activate osteoclasts) to increase Ca2+

1α25(Oh) D and PTH on the kidney (decrease Ca2+ and increase PO4 excretion in urine) and (increase Ca2+ resorption and reduce PO4 absorption in the renal tubules)

Vitamin D alone also, increases Ca2+ and PO4 absorption in the intestines *Important in Ostepenic or osteoporosis to increase bone density*

Question 18

Increased Ca2+ absorption from Vitamin D3 in the intestines

Answer 18

Reduces levels of PTH by increasing Ca2+ plasma levels preventing Bone reabsorption by osteoclasts

Bone reabsorption doesn’t occur without PTH and Vitamin D3

So this helps with Ca2+ absorption inhibiting bone resorption and allowing bone deposition

Question 19

What is the primary effect of Vitamin D

Answer 19

Fat-soluble, also controls gene expression for Ca2+ transport for absorption in the intestines

Question 20

Vitamin D and RXR

Answer 20

RXR can also associate with Vitamin D

RXR binds to a lot of things besides retinoic acid

Question 21

Vitamin E function

Answer 21

An electron scavenger

helps along with superoxide dismutase and glutathione peroxidase (especially in RBCs) and Catalase (these systems are in all cells

Question 22

Vitamin E AKA

Answer 22

α-tocopherol

Question 23

Vitamin K Function

Answer 23

mainly involved in the coagulation response

• a reduction-oxidation sequence of reactions
• clotting proteins need to be carboxylized by gammaglutamyl carboxylase and the electrons come from Vitamin K (Vitamin K Hydroquinone to vitamin K epoxide)
• Warfarin MOA is to prevent Vitamin K from being reduced again so that it can’t donate more e-s to prevent the activation of clotting proteins

Question 24

Thrombin MOA

Answer 24

vessal injury activate conversion of prothrombin to thrombin and thrombin cleaves fibrinogen to fibrin, fibrin lays down clot and activate platelets

The prothrombin to thrombin conversion would not occur if vitamin K wasn’t there to provide e-s

Not only thrombin but all of the clotting proteins

Question 25

A deficiency of Vitamin K

Answer 25

can only do one round of coagulation

impaired clotting cascade

Can lead to bleeding

Question 26

Clinical features of vitamin K deficiency

Answer 26

figure in notes

Question 27

INR

Answer 27

PT of patient / PT normal mean

Question 28

Atrial fibrillation

Answer 28

Atrium vibrates doesn’t contract properly

the blood is in stasis increasing clot potential

Warfarin - inhibits vitamin K reductase enzyme preventing Vitamin K from being reduced and preventing clotting factor activation