HNF 462 1st Edition Lecture 26Outline of Last LectureI. SourcesII. Digestion, Absorption, Transport, and StorageIII. MetabolismIV. Selenoproteinsa. Glutathione Peroxidase (GPX)b. Thioredoxin ReductaseOutline of Current LectureI. Selenium-Containing Protein vs. SelenoproteinII. Selenium ExcretionIII. Se RDA and DeficiencyIV. Se Toxicity and Assessment V. Iodine Sourcea. Iodization VI. Iodine Absorption, Transport, and StorageVII. Production of Thyroid HormoneVIII. Functions of IodineIX. Physiological Effects of Thyroid HormonesX. Iodine RDA and DeficiencyXI. Potassium Iodide for Radiation ProtectionXII. Nutrients that Affect Thyroid FunctionCurrent Lecture: Selenium (Se) Pt 2 and Iodine1. Selenium-Containing Protein vs. Selenoproteina. Se-Containing: contain selenium, but it is not located at their active site (ex. selenomethionine)i. Se-binding proteins: bind to Se/Se-containing amino acidThese 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.b. Selenoprotein: protein that has selenocysteine in its active site; a subset of Se-containing proteins2. Selenium Excretiona. Urine excretion maintains homeostasisb. Also excreted via feces, lungs, and skin3. Se RDA and Deficiencya. RDA:i. Adults = 55 micrograms/dayii. Increases with pregnancy and lactationb. Deficiencyi. Keshan Disease: Se-deficiency and virus leads to cardiomyopathy1. Virus attacks heart tissue2. Se+ mice with virus will not develop heart infection3. Se- mice with virus will die virus transferred to Se+ mouse will kill mouse (virus mutates in Se- host)4. Toxicity and Assessment a. Toxicityi. Selenosis: presents with skin problemsii. UL = 400 microgramsb. Assessmenti. Blood and plasma concentrationsii. Activities and concentrations of selenoproteins: with deficiency, selenoprotein concentration decreases and functions are impairediii. Urinary concentration5. Iodine Sourcea. Food content is varied depending of soilb. Iodization of salt to prevent deficiency 6. Iodine Absorption, Transport, and Storagea. Organic bound iodine freed via digestionb. Absorbed in the stomach efficiently bloodc. Travels as free iodide (inorganic form) in bloodd. Concentrates in thyroid gland via Na/I cotransporter7. Production of Thyroid Hormonea. Thyroid gland: colloid in middle surrounded by cell layerb. Transport of iodide into thyroid gland driven by sodium gradient across cell membranec. Thyroglobulin: inserts iodine onto its tyrosine residuesi. Creates Thg-MIT and Thg-DIT in colloidd. Creation of Thg-T3 (stacking of two Thg-MIT) and Thg-T4 (stacking of two Thg-DIT)i. Thyroid peroxidase (dependent on iron) catalyzes formation of T3 and T4e. Conversion of T4T3i. Active T3: Se-dependent enzyme removes iodine from the outer ringii. Inactive T3 (Reverse T3): Different Se-dependent enzyme removes iodine from inner ring1. Reverse T3 competes with active T3 for receptors; can decrease thyroid function if there is more reverse T3 than active T38. Functions of Iodinea. Synthesis of thyroid hormonesi. T4: inactive form, but contains more iodine compared to T3ii. T3: contains less iodine, but is more active compared to T4b. Transport of Thyroid Hormones into the bloodi. Bound to thyroxine-binding globulin, albumin, or transthyretinc. Biologically active forms are free T3/T4d. Regulation of DNA transcriptioni. Thyroid hormone receptors bind to DNAii. Recruit additional proteins to initiate/suppress transcription9. Physiological Effects of Thyroid Hormonesa. Increases metabolic rate and heat production by a negative feedback mechanismi. Hypothalamus senses low temperature or metabolic rate; secretes TRHii. TRH signals pituitary gland to secrete TSHiii. TSH stimulates thyroid function: thyroid releases T3 and T4 to increase metabolic rate and to raise body temperatureiv. Negative feedback: too much production of T3/4 will inhibit TRH and TSH to stop the overproduction of thyroid hormones1. If iodine deficient, there is not enough iodine to create T3/T4 to stop production of TRH and TSH; causes thyroid gland to grow due to constantly high level of TSH in gland10. Iodine RDA and Deficiencya. RDAi. Adults: 150 micrograms/dayii. Increases with pregnancy and lactationb. Deficiencyi. Goiter: large thyroid glandii. Cretinism: neurological consequences11. Potassium Iodide for Radiation Protectiona. Iodine-133 is radioactive: can cause thyroid cancerb. Prevention of cancer: high-dose supplement of potassium iodide to compete out radioactive form of iodinei. Saturates thyroid gland with iodine-127 so the gland cannot concentrate the radioactive form12. Nutrients that Affect Thyroid Functiona. Ironb. Seleniumc. Vitamin A: vitamin A deficiency reduces iodine uptake by thyroid glandd. Goitrogens: affect iodine uptake by the thyroid gland; can cause same symptoms of