Week 6: Vitamin A, C, D, E and K Flashcards
Anything yellow and orange
β-carotene derived
Vitamin A AKA
Retinol
β-Carotene->
Retinal
β-carotene structure
cut in half are 2 molecules of retinaldehyde
Processing of β-carotene
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
What is the connection between β-carotene and bile acids?
Both are hydrophobic so β-carotene is carried by bile acids for absorption into intestinal enterocytes
Retinol tissue-dependent uses
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
Retinol skin cream effects
increases the potential for the proliferation of skin cells
- enhances UV damage repair
- Reduce hyper-proliferation in Psoriasis
- Accelerate Wound healing
Main functions of retinoic acid
- 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
Vitamin C AKA
Ascorbic Acid
Functions of Vitamin C
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
Primary collagen
Collagen IV
Mechanism of scurvy
Vitamin C no collagen IV triple helix and crosslinking
Sources of Vitamin D
7-dehydrocholesterol with UV rays -breaks cholesterol ring-> Vitamin D3
or
Dietary Vitamin D3
Vitamin D3 processing
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
How to get active Vitamin D3
need sunlight or dietary D3
25(Oh) D and PTH
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*
Increased Ca2+ absorption from Vitamin D3 in the intestines
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
What is the primary effect of Vitamin D
Fat-soluble, also controls gene expression for Ca2+ transport for absorption in the intestines
Vitamin D and RXR
RXR can also associate with Vitamin D
RXR binds to a lot of things besides retinoic acid
Vitamin E function
An electron scavenger
helps along with superoxide dismutase and glutathione peroxidase (especially in RBCs) and Catalase (these systems are in all cells
Vitamin E AKA
α-tocopherol
Vitamin K Function
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
Thrombin MOA
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
A deficiency of Vitamin K
can only do one round of coagulation
impaired clotting cascade
Can lead to bleeding
Clinical features of vitamin K deficiency
figure in notes
INR
PT of patient / PT normal mean
Atrial fibrillation
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