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56 Cards in this Set
- Front
- Back
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What are the major dietary forms of Vit A?
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-Retinyl Esters
-B-carotene |
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What is the first step in Vit A absorption?
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-RE are cleaved by Enterocyte brush border REH's to yield Retinol + FFA
-B-carotene is just taken up by the enterocytes |
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What happens to Retinol once inside the enterocyte?
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LRAT esterifies it back to RE to be packaged into Chylomicrons
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What happens to B-carotene in the enterocyte?
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Converted to Retinal, then to Retinol, then to RE to be packaged into Chylomicrons
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What enzyme converts Retinol to Retinyl Ester (RE)?
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LRAT - Lecithin:Retinol acyl transferase
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What happens to chylomicrons?
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They get put into the bloodstream, cleaved by LPL, and chylomicron remnants go to the liver.
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What exactly does cleavage of B-Carotene produce?
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All-trans-retinal
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What enzyme cleaves B-Carotene?
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15,15'-monooxygenase
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What happens to Vit A from chylomicron remnants once they reach the liver?
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Retinyl Esters go into liver for storage or release.
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What must happen to RE in order to be stored in liver?
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They must be hydrolysed by REH to yield Retinol.
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What are the 3 possible fates of Retinol in the liver?
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1. Storage
2. Re-esterification by LRAT 3. Release as Transthyretin |
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What is Transthyretin?
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Retinol + RBP (Retinol binding protein)
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What type of enzyme can degrade retinol?
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Cytochrome P450
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What carries Vit A to target tissues?
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Transthyretin (TTR+RBP)
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What receptor takes up Retinol at target tissues?
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Megalin - a universal receptor.
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What happens to Retinol at target tissue cells?
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1. Binds CRBP (cellular retinol binding protein)
2. Oxidized to Retinoic Acid 3. Binds CRABP (cel. retinoic acid binding protein) |
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What are RAR and RXR?
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Nuclear Retinoid Receptors:
-Retinoic Acid Receptor -Retinoic Acid X receptor |
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What is the binding protein for Retinal?
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CRALBP
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What is the purpose of the cellular proteins that bind retinoids?
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To reduce their toxicity and serve as transporters.
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What retinoids bind
-RAR -RXR |
RAR = both 9-cis and All-trans
RXR = only 9-cis |
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What do RAR and RXR do?
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Bind together as heterodimers
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What does the heterodimer of RAR and RXR do?
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Binds RARE
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What is RARE?
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Retinoic Acid Receptor Element - in the promotor region of various genes.
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So what is the function of the retinoids?
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To bind nuclear receptors and regulate gene transcription.
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What gets regulated when RXR heterodimerizes with RAR?
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Embryonic development
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What other things can RXR heterodimerize with OTHER than RAR?
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-Thyroid hormone receptor
-Vitamin D receptor |
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What are 3 ways in which RARE can function?
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1. Repression of transcription
2. Derepression of trxn 3. Trxn activation |
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What causes repression of genes at the RARE?
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Corepressors bound to the ligand binding domain - because agonists are absent.
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What is the function of Corepressors?
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They link the heterodimer (RAR/RXR) to Histone Deacetylases (HDACs)
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What do histone deacetylases do?
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Deacetylate histones; results in chromatin condensation and gene silencing
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What causes gene derepression?
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Binding of agonists - induces HATs to acetylate histones
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What is the result of histone acetylation?
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Nucleosomal repulsion and CHROMATIN DECONDENSATION
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What causes the ultimate activation of transcrption by the RAR element?
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Binding of a third multi-subunit complex on top of the heterodimer RAR/RXR complex.
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What can the 3rd multi-subunit complex be?
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1. TRAP (thyroid hormone rec.)
2. DRIP Vit D Rec. interctng 3. SMCC (Srb) |
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What is Retinoic Acid given for / regulate?
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1. Development
2. Epithelial cell, immune, and reproductive functions. 3. Wound healing 4. Surgery patients on steroids |
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What is Rhodopsin made from?
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Opsin + 11-cis retinal
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How is 11-cis Retinal linked to Opsin to form Rhodopsin?
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Via a schiff's base
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2 Things that Vit A is involved with the eye in:
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-Rhodopsin formation
-Cone pigments |
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How does Vit A affect vision?
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It changes the wavelengths of light absorbed.
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What is the effect of light when it hits 11-cis retinal?
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Conformational change to All-trans-retinal
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What does the conformational change via light change rhodopsin into?
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Metarhodopsin
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What does Metarhodopsin do?
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Binds transducin for visual signal transduction propagation.
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What does the visual signal transduction in the retina involve?
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An absence of cGMP which closes a cGMP gated Na/Ca and signals the brain.
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What protein allows All-trans-retinal to be recycled back to 11-cis-retinal for vision?
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IRBP: interphotoreceptor binding protein
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What must happen to All-trans-retinal before it can bind IRBP?
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Reduction to All-trans-retinOL
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What does early-stage vitamin A deficiency result in?
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Stage I Night blindness
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What does later stage Vit A deficiency result in?
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-Abnormal epithelial cells
-Lack of Retinoic Acid -Keratinized skin & cornea -Abnormal immune function |
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What organ disease leads to vit A deficiency?
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Liver disease - alcoholism
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What results from EXCESS vitamin A?
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Blurry vision, birth defects, headache, loss of hair, scaly skin, etc.
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What is Tretinoin?
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Retinoic acid therapy for acne.
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What chronic disease is retinoic acid used for?
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Acute Promyelocytic leukemia
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What causes APL?
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Crossover between PML gene of Ch 15 and RAR gene of Ch 17
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What results from the T15,17?
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No heterodimer of RXR/RAR; instead just RAR/RAR.
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What is the absorption/transport of Vit A similar to?
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Fatty acid absorption and transport.
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Which retinoid is used in vision?
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11-cis retinal
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Which retinoids regulate gene expression?
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All-trans-retinoic acid
9-cis retinoic acid |
