Fat Soluble Vitamins PDF

Fat Soluble Vitamins Fat Soluble Vitamins  = · G * - E =...

Fat Soluble Vitamins Fat Soluble Vitamins  = · G * - E = - w - - - = - ·r · T = E - F - - = - · = - · · # - = ↑ ↑ cE = r - P g · W ⑤ O · - - e - - ↳ · = ↳ - = - - P n - T·n - I * - # - If * ↑ ·- · · - ↓ 8 -/ - M - Il · E d r ↑ = * Y e T - - · T · T ↳ G A ↓ ↓ Vitamins Early 20th century Vitamines, or “accessory growth factors” Casimir Funk discovered an anti-beriberi compound and named it vitamine Soon after, a butter fat extract was discovered and labeled fat- soluble A As each vitamine was discovered, it was assigned a letter The e was dropped due to lack of amine groups * Initially thought each vitamin had only one function in the body  ↑ Vitamins Vitamin A - Retinoids B1 Thiamin Vitamin B - Thiamin B2 RiboJavin Vitamin C – Ascorbic acid B3 Niacin Vitamin D - Calciferol B4 Adenine* Vitamin E – Tocopherols B5 Pantothenic acid - Vitamin F – EFAs B6 Pyridoxine Vitamin G – RiboJavin Vitamin H – Niacin B7 Biotin Vitamin I – N/A B8 Inositol* (chelating agent) Vitamin J – Choline B9 Folic acid Vitamin K – Phylloquinone B10 Para-Aminobenzoic acid (PABA)* B11 Salicylic acid* Vitamins with amines were grouped B Cobalamin 12 together as B Vitamins Fat Soluble Vitamins A, D, E, and K DeKa All dietary sources are absorbed and transported along with dietary fats Chylomicrons Remnants are taken up by liver Storage site di`ers for each vitamin Vit A – main storage is liver Vit D – main storage is blood, adipose, and muscle Vit E – main storage site is adipose tissue Vit K – cell membranes of kidneys, lungs, bone marrow, and adrenal glands Vitamin A Refers to a group of compounds possessing biological activity of all-trans retinol Retinol Retinal Retinoic acid Retinal ester Contain b-ionone ring and polyunsaturated side chain with a functional group Carotenoids are precursors to Vitamin A Over 600 exist, but less than 10% are used to make Vitamin A What happens if you eat too much carotene? Carotene Forms a-carotene b-carotene Lutein Vitamin A Absorption Found in plants and animals – primarily retinyl palmitate in animals, carotenoids in plants Vitamin A absorption is 70-90% Carotenoid absorption is 5-60% Less for uncooked and more for oils Carotenoid conversion decreases with higher intake – good Vitamin A status  Carotenoid Conversion b-carotene is converted to all-trans retinal Takes place in the enterocyte b-carotene 15,15’-mono-oxygenase Iron-dependent enzyme Retinal is then reduced by retinal/retinaldehyde reductase to retinol NADH-dependent enzyme Molecule must be re-esterihed to enable incorporation into chylomicron for circulation Cellular retinal binding protein (CRBP) Vitamin A Uses Vision – cones and rods Rods are more sensitive to light and use Vitamin A Light cleaves opsin from 11- cis-retinal Now you can see in the light Rhodopsin allows night vision Vitamin A dehciency can cause night blindness  One of the hrst signs of Vitamin A dehciency Impaired production of rhodopsin Night Over 1B have micronutrient dehciencies Blindness Vitamin A is the most dehcient nutrient in the body Usually seen in developing countries Golden rice  Vitamin A Uses Gene expression All-trans retinoic acid and 9-cis retinoic acid Transported to the nucleus through intracellular lipid binding proteins (iLBPs) found in cytosol Cellular retinoic acid-binding protein II carries vitamin to nuclear receptors – retinoic acid receptor (RAR) and retinoid x receptor (RXR) RAR – all-trans retinoic acid RXR – 9-cis retinoic acid RAR and RXR are present together forming homodimers (RXR-RXR) and heterodimers (RXR-RAR) Vitamin A Uses Cellular Di`erentiation Retinoic acid is needed for di`erentiation Epithelial cells are dependent on retinoic acid Growth Enhances cellular growth and survival Can inhibit apoptosis depending on interactions with PPARs Reproduction Retinol Immune function Bone mineral density – too much inhibits osteoblasts while promoting osteoclast function  Vitamin D AKA Calciferol Associated with skeletal growth and strong bones Rickets is preventable through intake of dietary fat-soluble Vitamin D Derived from a steroid – classihed as a seco-steroid Two main forms – ergocalciferol and cholecalciferol Ergocalciferol – D2 Primarily found in plants Cholecalciferol – D3 Found in animals Vitamin D Synthesis ~, Doesn’t Sunlight Make Vitamin D? 7-dehydrocholesterol synthesized in skin’s sebaceous glands and secreted to surface Conjugated set of double bonds in ring B absorb UVB photons at wavelengths of 285-320 nm causing ring B to open Unstable double bonds in ring B rearrange (thermal isomerization) creating D3 Excess exposure to sunlight causes 7- dehydrocholesterol to form lumisterol which is lost with skin Cutaneous D3 di`uses through skin to blood Vitamin D Transport ~50% absorbed through diet Main location of absorption is illium Chylomicrons transport majority while vitamin D-binding protein transport small amounts Main storage site is blood (except in obese, then adipose tissue) Vitamin D in the liver is hydroxylated by cytochrome P- 450 hydroxylases to form active vitamin D (D3) 25-hydroxylase (NADH dependent) hydroxylates at C25 to form 25-OH D before being released into the blood Vitamin D Transport Once in blood, 25-OH D is taken up by tissues Mostly kidneys 25-OH D binds to proximal tubules in kidneys where it is hydroxylated at position 1 to form 1,25-OH D, AKA calcitriol by 1-hydroxylase (NADH dependent) 1-hydroxylase in kidneys is tightly regulated by Parathyroid Hormone (PTH) and hbroblast-like growth factor (FGF) 23 After conversion, 1,25-OH D travels through blood to target tissues Vitamin D Uses Nongenomic: Mediated by activation of intracellular signaling Membrane associated rapid response steroid-binding proteins (MARRS) stimulate: Mitogen-activated protein kinase (MAP K), protein kinase C, cyclic AMP, tyrosine kinase and many other intracellular pathways Increased calcium uptake Increased intracellular calcium concentration Transcellular calcium Jux Vitamin D Uses Genomic: Di`use from cytosol to nucleus Binds to nuclear Vitamin D Receptors (VDR) Usually exist as a heterodimer (with RXR) Activate Vitamin D Response Elements, found in promoter regions of target genes Can inhibit or enhance mRNA translation Genes regulated by Vitamin D typically involve calcium homeostasis Osteocalcin, osteopontin, calbindin, Ca2+-ATPase, etc. Vitamin D Uses Primary role is calcium homeostasis – whether in blood, bone, muscle, etc. Helps with normal cell growth, di`erentiation, and proliferation Can help prevent malignancy through down-regulating cancer cell growth and inducing apoptosis Useful in psoriasis due to epidermal cell di`erentiation Maintenance of type II muscle hbers Increase transcription of genes for ATPase pumps in sarcoplasmic reticulum Roles in blood pressure, pancreatic b-cell protection, insulin secretion, and autoimmune diseases (linked with inadequate Vit D status) Vitamin E 8 compounds in total Tocopherols Saturated side chains with 16 carbons Tokos = childbirth Phero = to bring forth Tocotrienols Unsaturated side chains with 16 carbons Each class di`ers in number and location of methyl groups on rthe chromanol ring Most biologically active form is a-tocopherol Vitamin E Forms Vitamin E Uses Primary function is an antioxidant Maintains integrity in cell membranes Prevents oxidation of unsaturated fatty acids in acids in phospholipids Lungs, brain, and erythrocytes at greatest risk for oxidation Brain uses ~20% total body oxygen Hydroxyl group in chromane ring is the main reason for antioxidant ability Provides hydrogen ions to free radicals  Hydroxyl Radicals Initiation typically begins with initiator such as a free radical Hydroxyl radicals are highly reactive – take electrons from their surroundings Usually taken from organic molecules If PUFA from cell membrane, damage occurs Methylene groups are main targets for proton abstraction Without termination, thousands of lipid peroxides may arise from one radical, resulting in massive cellular damage Vitamin E as a Radical Stabilizer Vitamin E can accept the radical and still be a stable structure Can then react with other molecules to stabilize the radical Allows reuse of Vitamin E molecule Vitamin K Named after Dutch word, koagulation 2-methyl; 1,4-napthoquinone ring with a substitution at position 3 Naturally occurring forms are phylloquinone and menaquinone Phylloquinone has a phytyl group at position 3 of the ring Menaquinone has an unsaturated multiprenyl group at position 3 Overview of Blood Clotting Factor XII adsorbs onto a surface such as collagen which is exposed with injury Upon contact, factor XII becomes activated Factor XIa activates IXa which is Vitamin K dependent Factor IXa activates X which is also Vit K dependent Factor X converts to Factor II, prothrombin (vitamin K dependent) to thrombin Thrombin alters hbrogenin to hbrin for clot formation Factor XIIIa, hbrin stabilizing factor creates insoluble hbrin for hnal clot formation Questions?