HNF 462 1st Edition Lecture 11Outline of Last LectureI. StructureII. AbsorptionIII. MetabolismIV. BioavailabilityV. TransportVI. Storage and ExcretionVII. Functionsa. Coenzymei. Schiff Baseb. Transaminationc. Decarboxylationd. Deaminatione. Synthetic ReactionsVIII. DeficiencyOutline of Current LectureI. Forms of Vitamin AII. AbsorptionIII. StorageIV. TransportV. ExcretionVI. Functionsa. Eye sightb. Cellular Differentiation/Growth and DevelopmentVII. Deficiency and ToxicityVIII. ReproductionThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.IX. SupplementsX. AssessmentXI. CancerCurrent Lecture: Vitamin A1. Forms of Vitamin Aa. Retinyl-esters: carry fatty acidsi. Pre-formed vitamin A in our bodies—biologically active formii. Can get from animal productsiii. ARAT and LRAT remove fatty acids to form retinolb. Retinol: alcohol formi. Can get from animal productsii. Retinol dehydrogenase converts between retinol and retinalc. Retinal: Aldehyde formi. Can get from animal productsii. RALDH converts retinal to retinoic acid in an irreversible reactiond. Retinoic Acid: carboxylic acid formi. Can get from animal Productse. B-Carotene: plant formi. 15,15 mono oxygenase cleaves beta-carotene into 2 retinols2. Absorptiona. Pancreatic enzymes cleave fatty acids to yield retinolb. Bile micelles chylomicron passive diffusion into the lymphatic system subclavian vein blood stream liver3. Storagea. Stored primarily in the liver as retinyl-esterb. Secondary storage in adipose tissuec. Small cellular reserves: bound to proteinsi. CRBP: retinolii. CRABP: retinal4. Transporta. Transported as retinol in the serumb. Serum retinol is maintained by liver storesc. Zinc deficiency and protein status affect transportd. Travel bound to RBP and TTR proteins in a 1:1:1 ratio5. Excretiona. Kidney can’t filter protein-bound vitamin Ab. Either need to oxidize retinol or conjugate it to gucuronic acid to make more soluble in an aqueous environment. Then, can be excreted through the urine, or transferred to bile where it will be excreted in feces6. Functionsa. Eye sighti. Vitamin A in the form of 11 cis retinaldehyde, used in the sensing of lightii. Bent structure of vitamin A is conjugated to opsin (APO protein) to form rhodopsin (HOLO protein). This is then hit with an energy source (light), and the structure of vitamin A straightens out. A conformational change in the protein causes a nerve impulse to be sent to the brain for the eyes to adjustiii. Conformational change from 11 cis retinaldehyde to all trans retinoic acid canbe reversedb. Cellular Differentiation/Growth and Developmenti. In the form of All-trans retinoic acidii. Cellular differentiation through gene regulation7. Deficiency and Toxicitya. Deficiencyi. Night Blindness: increased time needed to adjust to low light levels. Can be reversed with vitamin A supplementationii. Xeropthhalmia: Cannot be reversed with supplementation. Symptoms—Bitot’s spots, loss of goblet cells (produce mucus), dry/scarred eyes1. Due to decreased mucus production: increased infection, anorexia/growth stunting, brittle/dry/cracked skiniii. People with fat malabsorption disorders are at risk for vitamin A deficiencyb. Toxicity:i. Acute and chronic symptoms are similar to deficiency symptoms1. U Shaped Curve: at high and low ends of vitamin status, have the same risk of diseaseii. Chronic toxicity can only be caused by over-supplementation8. Reproductiona. Critical in developing embryos because of gene expression (all-trans retinoic acid)b. Vitamin A can be teratogenic (toxic) at high doses9. Supplementsa. Beta-carotene is more bioavailable from supplements than from food sourcesb. High doses of B-carotene will cause orange skin pigmentation10. Assessmenta. Blood concentrationsb. Eye/vision screeningsc. Liver biopsies (if deficient, then liver stores are low)11. Cancera. ProMyelocytic Leukemia (PML/AML/APL): translocation of gene on chromosome 15; can be treated with high-dose vitamin Ab. Beta-carotene Supplementation and Lung
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