Vitamin A Soprano Flashcards
What is the difference between Vitamin A and Retinoid terminology?
Vitamin A- all the dietary/naturally occurring forms of Vitamin A that are structurally related to retinol
Retinoids- includes the naturally occurring vitamins as well as the synthetic compounds with retinoid activity (may or may not have similar structure)
B-Carotene
A carotinoid with provitamin A activity. Looks like 2 molecules of retinol squished together. In the gut it is cleaved into Vitamin A
What kind of Vitamin A do plants provide?
B-carotenes
What kind of Vitamin A do animals provide?
Retinyl Esters
What are the dietary forms of Vitamin A?
B-Carotenes
Retinyl Esters
Small amount of retinol
Where is Vitamin A absorbed?
The small intestines
Describe absorption of B-Carotene into the intestinal cells
- B-carotene is cleaved into 2 molecules of retinal by enzymes in the SI brush border
- Inside the intestinal epithelium, retinal is reduced to retinol
- retinol binds to CRBP (involved in movement in the cytoplasm)
- LRAT esterifies it to retinyl ester.
- retinyl esters are packaged into chylomicrons that also contain FA and fat soluble vitamins.
- chylomicrons carry retinyl esters in the circulation
- goes to adipose tissues where TG are removed but retinyl esters remain
- the chylomicron remnant holding the retinyl ester is delivered to the liver
What form of Vitamin A is absorbed into the body?
retinol
What form of Vitamin A is functional?
Retinoic Acid
What is the function of retinal (aka retinaldehyde)?
night vision
What is the function of retinol?
the dietary, storage and transport form of Vitamin A
What is the function of the liver?
storage, trafficking, and regulation of release
Describe the absorption of retinyl esters at the hepatocye
- chylomicron remnant is taken up by the hepatocye
- retinyl ester is hydrolzyed to free retinol
- retinol binds CRBP which moves it around in the hepatocyte cytosol
- CRBP-retinol are transported to the stellate cell (Ito cell) where retinol is stored
What is CRBP?
cellular retinal binding protein present in the cellular cytoplasm. Retinol is insoluble and must always be bound to a binding protein
What is RBP?
retinol binding protein, used for transporting retinol to target tissues
What is TTR?
transthyretin, a plasma protein that is made by the hepatocyte and is a tetramer that binds one molecule of retinol and T4. it complexes with RBP-retinol and functions to make sure it isn’t filtered at the glomerulus.
How is retinol delivered to target tissues from the hepatocyte?
- RBP binds to retinol
- TTR complexes with RBP-retinol
- leaves hepatocyte and enters the circulation
Describe retinol uptake and metabolism at the target tissues
- via STRA6 retinol is taken up into the target tissue while RBP and TTR do not enter the cell
- retinol is bound by CRBP
- retinol can then be stored as a retinyl ester or oxidized to retinal and then retinoic acid
- RA binds to CRABP
- RA can enter the nucleus and bind to transcription factors RAR/RXR bound to RARE response elements in the promotor region affecting transcription and translation
Describe the metabolism of retinol to retinoid acid, which process is and is not reversible?
- retinol is hydrolyzed to retinal (aka retinaldehyde)
- retinal is hydrolyzed to retinoid acid
* *retinol to retinal is a reversible process, but once oxidized to retinoid acid, it cannot be reversed to retinal.
How do you get rid of retinoic acid?
either is used at the tissues or Cytochrome P450 converts it to a form that can be excreted in the urine
If Vitamin A deficient and supplement with RA, what pathology can occur?
Can supplement patient with retinoic acid and everything else will be normally restored, but since retinoic acid can’t be reversed to retinaldehyde, patient won’t have night vision. Also spermatogenesis will be impaired since RA can’t pass the testes/blood barrier
What are the functions of retinoic acid?
- immune responses
- eye maintenance and integrity of the cornea
- embryonic development
- Spermatogenesis- only retinol can pass the testes/blood barrier, but once past then converted to RA which carries out the main functions
- maintenance and differentiation of all epithelial tissue
Can night vision be restored?
yes, if 11-cis retinAl is supplemented in the diet.
What is xerophthalmia?
cornea requires RA to maintain its normal differentiated state. If vitamin A deficient, then cornea gets lesions and conjunctival membranes are destroyed resulting in permanent blindness.
How does xerophthalmia occur?
starts as simple columnar and eventually changes to keritonized stratified squamous where no more mucus is able to be produced resulting in a cracking cornea
What are the transcription factors for retinoic acid?
RAR and RXR can form a heterodimer or homodimer (less common) that sit in the nucleus on the RARE sequence in the promotor region. When RXR can bind corepressors. When RAR binds RA, the corepressors are kicked off and coactivators bind. They are ligand-activated and when RA binds, rate of transcription of the genes can be controlled
What are the ligands for RXR and RAR?
RXR- can only bind 9-cis RA (corepressors can bind here)
RAR- (retinoic acid receptor) can bind all-trans RA and 9-cis RA
**each have their own alpha, beta and gamma forms.
Describe how night vision is accomplished?
- retinol enters the retinal pigment epithelial cell and is metabolized to 11-cis retinal.
- 11-cis retinal enters the neural retina and binds to opsin forming rhodopsin
- when light hits rhodopsin, it is cleaved into opsin and all-trans retinal, generating a neural signal
What is the function of albumin?
can transport a small amount of retinol in the blood
What are the signs of Vitamin A deficiency?
First, night-blindness (nyctalopia)
Second, xerophthalmia
third, inability to fight infections, particularly measles
What are the acute and chronic signs of Vitamin toxicity?
acute: nausea, vomiting, blurred vision, headache, dizziness, loss of muscular coordination and death
chronic: birth defects, liver abnormalities, reduced bone mineral density
What are the pharmacological skin applications of vitamin A?
all-trans RA (topical acne)
adapalene (topical acne)
13-cis RA accutane (oral cystic acne)
What are some side effects of accutane?
birth defects, liver defects and abnormalities, some links to mental health issues. No effect of spermatogenesis.
What are some uses for synthetic vitamin A products?
leukemia, lymphoma, epithelial cell cancers, diabetes and atherosclerosis
What are some retinoid teratogenicities?
(birth defects) due to retinoids include craniofacial, brain, ears, eye, facial palsy and clefts, cardio-aoritc, limb reduction, gastrointestinal , urinary
