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3rd Year Nutr class Summary (MIDTERM).pdf

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NUTR 3210
Manfred Brauer

OXIDANT DEFENSE - vitamin e - vitamin c - selenium - niacin - riboflavin - copper - zinc - manganese HORMONE RECEPTORS Big HEALTH implications - iodide - vitamin a - vitamin d - calcium - vitamin k - phosphorus - fluoride Enzyme COFACTORS - thiamin - niacin - riboflavin - b6 - folate - b12 - biotin - pantothenic acid STEROID HORMONE RECEPTORS intracellular proteins, regulate gene expression - Type I: Cytosolic; responds to steroid hormones like estrogens, testosterone, progesterone, glucocorticoids and mineralcorticoids - Type II: Nuclear; were found to have similar structure, but bind to steroid and non-steroid ligands like thyroid hormone, retinoic acid and calcitriol (1,25-dihydroxy vitamin D) o Critical to the nutrient functions of Vitamin A, Vitamin D and thyroid hormones IODINE (hormone receptor) - Generally low in most foods, salt iodized with potassium iodine - converted to iodide in gut, which is the form we find in circulation - Iodide; used to synthesize thyroid hormones T3 & T4 - If Iodide is deficient, we lead to a goiter (hyperplasia of the thyroid) from prolonged elevation of Thyroid Stimulating Hormone (TSH) - T3 regulated metabolic rate and growth in many tissues through the interaction w/ the Thyroid Hormone Receptor - When hypothalamus sense low T3, neural signals to the pituitary cause release of TSH THYROID STIMULATING HORMONE - most of the circulating form is T4, but T3 is bioactive form - Liver converts t4 to t3 - T3 binds to nuclear receptors, forming transcription factors, which bind to response elements in promotor regions of DNA, leading to formation of new mRNA for specific proteins - Free THRs (lacking bound t3) have depressing effects of gene expression Cretinism irreversible mental retardation from fetal hypothryroidism VITAMIN A (hormone receptor) - night blindness - Alcohol form is retinol; carotenes were recognized as the plant form of the vitamins o A plant provitamin is the form of vitamin A produced by plants that when concumes by anilams is converted in vivo into the bioactive vitamin - retinoids, comprise retinol, retinal and retinoic acid - Beta carotene is most active - 15,15 converts first to two monecules of RetinAL, which converts to retinol o all-trans retinAL -> 11-cis retinal (night vision) o all trans retinAL -> all-trans retinoic acid -> binding to RAR, RXR (control of gene expression) Beta carotene has two fates: 1) chylomicron for storage not controlled when stored in adipose tissue 2) retinyl palmitate to form retinol in the liver Retinol-RBP is not Active but it is a homeostatic set point. Its a precursor to the active hormone retinoic acid - Target tissue converts retinol to 1) 11-cis retinal (retina) 2) retinoic acid (other) beta carotene -> retinal -> retinol -> retinyl palmitate (palmityl CoA activates) -> chylomicron - Cells obtain retinol from blood and form retinoic acid, which enters the blood and activates the RAR and RXR NIGHT BLINDNESS (rhopopsin) reversible Bitots spots, a build up of keratin debris in the cojunctive Impaired Epithelial Cell Differentiation permanent blindness and life threatening infections like pneumonia Vit.A TOXICITY most severe is liver cell death. Retinyl palmitate is stored in the stellate cells of the liver, the cells will get to full capacity with excess vitamin A intake VITAMIN D (Hormone Receptor) Sources: 1) From plants (limited importance) Ergosterol > ergocalciferol (D2) -- just needs ultraviolet 2) From animals 7-dehydrocholesterol -> cholecalficerol (D3) -- needs ultraviolet then heat 3) Sun 4) Supplements (D3 form) fat soluble so better absorbed with lipid 5) Fortification; relatively low levels in milk and margarine 1,25-diOH vit D = Calcitriol, the active form of Vitamin D 25-OH-D is a precursor to active vitamin D (1,25-diOH vitamin D aka calcitriol) so its maintained at set levels to ensure active form can be made immediately Calcitriol is synthesized in the kidney in response to low blood calcium and PTH secretion it enters the cells and binds to the vitamin D receptor (VDR-nuclear) and then acts as a transcription factor in the regulation of gene expression It also binds to a cell surface receptor, causing rapid regulation o existing proteins, including calcium transporters Proteins induced by vitamin D are often required to BIND CALCUIM, and need to be gamma-carboxylated (vitamin K) to be able to do this VITAMIN D/CALCIUM STORY ABSORption occurs in the small intestine. Minerals need transporters to get through the membrane into the mucosal cell, and more transporters to get it out into the portal blood. Proper absorption depends on expression of a calcium binding protein in epithelial cells REABsorption occurs in the kidney. Small molecules like Calcium circulate in blood and eventually reach the kidney, where they can end up in the urine reabsorption removes the molecules from the filtrate and gets them back into the blood RESORption occurs in the bone. Dissolving bone to release calcium into the blood stream. Osteoclasts resorb, osteoblasts build CALCUIM HORMONAL CONTROL SYSTEMS Parathyroid hormone secreted by parathyroid glands - serves to increase blood calcium - stimulates production of calcitriol in kidney (activates 1-hydroxylase) - stimulates bone resorption (activation of osteoclasts) - maximizes tubular reabsorption of calcium in kidney Vitamin D- 5 sources, serves to increase blood calcium - stimulates resorption of bone (immediate) - facilitates absorption of calcium from SI (short term response) - maximizes tubular reabsorption of calcium in kidney (short term response) Calcitonin ; secreted by thyroid parafollicular cells - serves to decrease blood calcium - suppresses tubular reabsorption o
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