lecture 17: vitamin A Flashcards
vitamin A
compounds that exhibit the biological activity of retinol the alcoholic form of vitamin A
fat soluble
vision, immunity, metabolism, cell proliferation
carotenoids
plant derived precursors for vitamin A, can be converted to retinol in animals
how is vitamin A stored?
stored as retinyl esters in the liver
major forms of vitamin A in the diet
retinyl esters: animal sources – hydroyzed in lumen
carotenoids: plants
carboxylester lipase
secreted into intestinal lumen from pancreas to hydrolyze short-chain retinyl esters
retinyl ester hydrolase
hydrolyzes retinyl esters with long FA chain
brush border membrane of small intestine
absorption of vitamin A
retinyl esters are hydrolyzed in lumen
absorbed β-carotene cleaved into two molecules of retinal
Formation of retinyl esters > packaged into chylomicrons, secreted to tissues
ARAT and LRAT
retinol > retinyl esters
reformation fo retinyl esters after absorption
major site of vitamin A storage
liver
how is vitamin A transported
retinyl esters transported in chylomicrons and secreted to tissues
retinol binding protein
water soluble proteins that carry retinol through circulation
interactions of retinoids with these proteins retard their degradation, decrease their concentrations in membranes, and increase their concentrations in aqueous spaces
hydrophobic B barrel
retinol binding site of RBP
The main site of synthesis and secretion of RBP
liver
11-cis-isomer of retinal
visual transduction
physiological function of RA
regulate transcription of multiple genes
rhodopsin
senses light, membrane protein located in photoreceptor cells, uses 11-cis-retinal as chromophore
11-cis-retinal and vision process
light sensed by rhodopsin, which uses 11-cis-retinal as its chromophore
absorption of a photon by 11-cis-retinal triggers hyperpolarization of plasma membrane and isomerization to all-trans form
intermediate conformation interacts with transducin, exchange of GDP for GTP
bleached rhodopsin can be regenerated by replenishing 11-cis-retinal supply from RPE cells
transducin
G protein, interaction with conformational intermediate of rhodopsin leads to exchange of transducin-bound GDP for a GTP
GTP-bound transducin activates phosphodiesterase > breakdown of cGMP to inactive GMP
phosphodiesterase
breaks down cGMP to inactive GMP > closes sodium channels and hyperpolarization of plasma membrane
retinoic acid function
regulation of cell proliferation and differentiation
all-trans-RA
enhances transcription of target genes by activating RAR and PPAR
retinoid nuclear receptors
RAs regulate gene expression by activating these receptors
bind to DNA recognition sequence, facilitate rate of gene transcription
9-cis-RA
activates RXRs
RAR and PPAR heterodimers
associate with RXR to form heterodimers, homodimers do not readily form
RXR-RAR and RXR-PPAR
RXR heterodimers
regulated by more than one type of ligand
RXRs = master regulators of several signaling nutrients and hormones
ex. vitamin D VDR, thyroid hormone TR
nonpermissive vs permissive heterodimers
nonpermissive: binding of one ligand does not permit binding of the other
permissive: requires binding of both ligands
co-regulatory proteins
function as transcriptional corepressors in the absence of ligands
upon ligand binding, receptors dissociate corepressors and recruit coactivators
vitamin A deficiency
mainly plant based diet, little dietary fat (little absorption of fat-soluble vitamins)
drying of cornea > damage to cornea > blindness
keratinization of tracheal epithelium, thinning of intestinal epithelium
