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56 Cards in this Set

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  • Back
What are the major dietary forms of Vit A?
-Retinyl Esters
What is the first step in Vit A absorption?
-RE are cleaved by Enterocyte brush border REH's to yield Retinol + FFA
-B-carotene is just taken up by the enterocytes
What happens to Retinol once inside the enterocyte?
LRAT esterifies it back to RE to be packaged into Chylomicrons
What happens to B-carotene in the enterocyte?
Converted to Retinal, then to Retinol, then to RE to be packaged into Chylomicrons
What enzyme converts Retinol to Retinyl Ester (RE)?
LRAT - Lecithin:Retinol acyl transferase
What happens to chylomicrons?
They get put into the bloodstream, cleaved by LPL, and chylomicron remnants go to the liver.
What exactly does cleavage of B-Carotene produce?
What enzyme cleaves B-Carotene?
What happens to Vit A from chylomicron remnants once they reach the liver?
Retinyl Esters go into liver for storage or release.
What must happen to RE in order to be stored in liver?
They must be hydrolysed by REH to yield Retinol.
What are the 3 possible fates of Retinol in the liver?
1. Storage
2. Re-esterification by LRAT
3. Release as Transthyretin
What is Transthyretin?
Retinol + RBP (Retinol binding protein)
What type of enzyme can degrade retinol?
Cytochrome P450
What carries Vit A to target tissues?
Transthyretin (TTR+RBP)
What receptor takes up Retinol at target tissues?
Megalin - a universal receptor.
What happens to Retinol at target tissue cells?
1. Binds CRBP (cellular retinol binding protein)
2. Oxidized to Retinoic Acid
3. Binds CRABP (cel. retinoic acid binding protein)
What are RAR and RXR?
Nuclear Retinoid Receptors:
-Retinoic Acid Receptor
-Retinoic Acid X receptor
What is the binding protein for Retinal?
What is the purpose of the cellular proteins that bind retinoids?
To reduce their toxicity and serve as transporters.
What retinoids bind
RAR = both 9-cis and All-trans

RXR = only 9-cis
What do RAR and RXR do?
Bind together as heterodimers
What does the heterodimer of RAR and RXR do?
Binds RARE
What is RARE?
Retinoic Acid Receptor Element - in the promotor region of various genes.
So what is the function of the retinoids?
To bind nuclear receptors and regulate gene transcription.
What gets regulated when RXR heterodimerizes with RAR?
Embryonic development
What other things can RXR heterodimerize with OTHER than RAR?
-Thyroid hormone receptor
-Vitamin D receptor
What are 3 ways in which RARE can function?
1. Repression of transcription
2. Derepression of trxn
3. Trxn activation
What causes repression of genes at the RARE?
Corepressors bound to the ligand binding domain - because agonists are absent.
What is the function of Corepressors?
They link the heterodimer (RAR/RXR) to Histone Deacetylases (HDACs)
What do histone deacetylases do?
Deacetylate histones; results in chromatin condensation and gene silencing
What causes gene derepression?
Binding of agonists - induces HATs to acetylate histones
What is the result of histone acetylation?
Nucleosomal repulsion and CHROMATIN DECONDENSATION
What causes the ultimate activation of transcrption by the RAR element?
Binding of a third multi-subunit complex on top of the heterodimer RAR/RXR complex.
What can the 3rd multi-subunit complex be?
1. TRAP (thyroid hormone rec.)
2. DRIP Vit D Rec. interctng
3. SMCC (Srb)
What is Retinoic Acid given for / regulate?
1. Development
2. Epithelial cell, immune, and reproductive functions.
3. Wound healing
4. Surgery patients on steroids
What is Rhodopsin made from?
Opsin + 11-cis retinal
How is 11-cis Retinal linked to Opsin to form Rhodopsin?
Via a schiff's base
2 Things that Vit A is involved with the eye in:
-Rhodopsin formation
-Cone pigments
How does Vit A affect vision?
It changes the wavelengths of light absorbed.
What is the effect of light when it hits 11-cis retinal?
Conformational change to All-trans-retinal
What does the conformational change via light change rhodopsin into?
What does Metarhodopsin do?
Binds transducin for visual signal transduction propagation.
What does the visual signal transduction in the retina involve?
An absence of cGMP which closes a cGMP gated Na/Ca and signals the brain.
What protein allows All-trans-retinal to be recycled back to 11-cis-retinal for vision?
IRBP: interphotoreceptor binding protein
What must happen to All-trans-retinal before it can bind IRBP?
Reduction to All-trans-retinOL
What does early-stage vitamin A deficiency result in?
Stage I Night blindness
What does later stage Vit A deficiency result in?
-Abnormal epithelial cells
-Lack of Retinoic Acid
-Keratinized skin & cornea
-Abnormal immune function
What organ disease leads to vit A deficiency?
Liver disease - alcoholism
What results from EXCESS vitamin A?
Blurry vision, birth defects, headache, loss of hair, scaly skin, etc.
What is Tretinoin?
Retinoic acid therapy for acne.
What chronic disease is retinoic acid used for?
Acute Promyelocytic leukemia
What causes APL?
Crossover between PML gene of Ch 15 and RAR gene of Ch 17
What results from the T15,17?
No heterodimer of RXR/RAR; instead just RAR/RAR.
What is the absorption/transport of Vit A similar to?
Fatty acid absorption and transport.
Which retinoid is used in vision?
11-cis retinal
Which retinoids regulate gene expression?
All-trans-retinoic acid
9-cis retinoic acid