Extra credit assignment

1. Extra credit assignment • "High-sensitivity serum C-reactive protein levels in subjects with or without myocardial infarction or periodontitis" (2005) Journal of Clinical Periodontology 32:219 by Persson, Pettersson, Ohlsson and Renvert • Web address is available on blackboard. http://www.blackwell-synergy.com/doi/full/10.1111/j.1600-051X.2005.00648.x

2. Section 10: Nutrients and their functions • Vitamin A 01/24/06

3. Vitamin A • RDA is 0.8 mg for women and 1.0 mg for men. • Fat-soluble; uptake depends on bile salts. • Light sensitive. • Temperature stable. • Carotenes from plants are converted to vitamin A. 1

4. Roles • Development (growth and cell differentiation) and maintenance of epithelial tissue. • Enamel • Eyes • Genitourinary Tract • Lungs • Skin • Toxic at high levels. • Acute • Chronic (stored in liver) 2

5. Vitamin A Derivatives • Retinol is esterified for storage. • It is oxidized to the aldehyde or acid level for use in epithelial tissues. • Conformations shown here are all-trans. 3

6. Retinoid Uptake • All-trans retinol is produced from carotene by oxidation in the intestinal epithelium, and from retinyl fatty acid ester by hydrolysis. 4

7. Structures and Conformations Derived from Vitamin A • These reactions occur intracellularly in various epithelial tissues. 5

8. Cell Differentiation • Retinyl ester is hydrolyzed to retinol. • Retinol is oxidized to all-trans retinoic acid (RA), a morphogen. • RA binds Cellular Retinoic Acid Binding Protein (CRBP) to form RA.CRBP, which buffers intracellular free [RA]. • RA binds a nuclear hormone receptor that is bound to DNA. • This triggers the release of a corepressor bound to the nuclear hormone receptor, and induces expression of the associated gene as part of the control of cell differentiation. « « RA RAR-repressor • RA nuclear hormone receptor is a member of a superfamily, which includes DNA binding receptors for thyroxine, steroids and vitamin D derivatives. 6

9. Vitamin A: Epithelial Cell Development • Vitamin A is required for the development and maintenance of all epithelial tissue, including enamel-making cells. • Mesodermal cells and odontoblasts transiently express genes for production of RA, CRBP’s and RAR. • A signal (Q) triggers the development of mesodermal cells into odontoblasts, which then signals back (?) to the ameloblasts to start making enamel. • RA is implicated but the mechanisms communication are still not known. 7

10. Light and Matter • A chromophore (“A” here) absorbs light only over a limited wavelength range. • After absorption, A is temporarily excited (A*). • A* relaxes back to A, or to a new structure (B here). • Photon energy and A structure must “match.” 8

11. Retinal is Visual Pigment of Rhodopsin • In the dark, the 11-cis conformation of retinal binds to the protein opsin and forms a protonated Schiff base with a lysine to make rhodopsin. • This shifts the absorption maximum of the retinal from 278 nm to 500 nm. 9

12. Rhodopsin • A speculative structure. • The retinal is in red. • There are seven transmembrane a-helices. • from Stryer (1986) Sci. Amer. 10

13. Rhodopsin - Light Reaction • Rhodopsin absorbs a photon (in the visible range) • 11-cis retinal changes to unprotonated all-trans retinal. • Rhodopsin changes conformation (R to R*). • R* is less stable. 11

14. Light Detection • Disc bilayers have a high density of rhodopsin molecules. • There is a high probability of a photon hitting a rhodopsin while traversing the stacked discs. • A single photon is detectable. 12

15. Retinal Conformations in the Visual Cycle • R absorbs a photon, becoming R*. • R* reactions lead to excitation of the optic nerve. • R* dissociates (relaxes) to opsin and all-trans-retinal. • All-trans and 11-cis retinal are in equilibrium. • 11-cis retinal binds to opsin by a Schiff base linkage 13

16. Visual signal transduction cGMP - • Light converts R to R*. • R* binds transducin, causing Ta to dissociate and bind GTP. • Ta-GTP complex binds and activates cGMP phosphodiesterase (inhibitory subunit dissociates). • Active cGMP phosphodiesterase reduces [cGMP]. • cGMP dissociates from Na-Ca channel, reducing ion influx and causing hyperpolarization. Fig. 32-25 14

17. cGMP maintains open Na+ channel in the cell membrane. Signal Transduction Mechanism • Transducin = T = TTT (a G-protein) • PDE = phosphodiesterase (active as PDE*-T-GTP). • R* is available to activate PDE by this mechanism until R* is phosphorylated by rhodopsin kinase (RK) and binds arrestin (A). (The inactivated R* dissociates to R and retinal.) 15

18. Hyperpolarization • Dissociation of cGMP causes sodium channels to close. • Lower Na+ starts membrane hyperpolarization. • Lower Ca2+ stimulates guanylate cyclase for recovery of [cGMP]. 16

19. Color Vision • Rod rhodopsin absorbance is broad and sensitive. • Cone rhodopsins have retinal attached to different opsins, which make them absorb over narrow (color specific) ranges. • Cone rhodopsins are also less sensitive. 17

20. Chlorophyll • Objects appear as the color that they do not absorb. • Chlorophyll absorbs strongly in the blue and red regions of the visible spectrum. • This leaves green light for the cones. 18

21. Next topic: Vitamin K and blood clotting.