HNF 462Exam # 2 Study Guide Lectures: 11 - 21 Lecture 11Vitamin A1. Forms:a. Retinyl-Esters: carry fatty acidsi. Biologically active formii. ARAT and LRAT remove fatty acids to form retinolb. Retinol: alcohol formi. Retinol dehydrogenase converts between retinol and retinal (reversible reaction)c. Retinal (Retinaldehyde): aldehyde formi. RALDH converts to retinoic acid (irreversible reaction)ii. Functions in eye sight—11-cis retinalall-trans retinoic acid by conjugation of opsin protein to rhodopsind. Retinoic Acid: Carboxylic acid formi. Functions in gene regulatione. B-Carotene i. Plant formii. 15,15 mono oxygenase cleaves into 2 retinols2. Absorptiona. Absorbed in retinol formb. Fat-soluble vitamin: absorbed in the bile micelles chylomicron liveri. A diet low in fat will decrease the absorption of fat-soluble vitamins3. Storagea. Primarily stored in liver as retinyl-ester b. Secondary storage in adipose tissuec. Small cellular reserves: bound to proteinsi. CRBP: binds to retinolii. CRABP: binds to retinal4. Transporta. In serum as retinol (serum levels maintained by liver)b. Zinc deficiency and protein status affect transportc. Travel bound to RBP and TTR proteins (in a 1:1:1 ratio)5. Excretiona. In order to be excreted, vitamin A must either be oxidized to retinol or conjugated to gucuronic acid to make it more soluble.b. Excreted through urine or transferred to bile where it is excreted via feces6. Deficiencya. Deficiency:i. Night blindness: increased time to adjust to low levels of light due to decreased retinal; reversibleii. Xerophthalmia: Bitot’s spots, loss of mucus producing (goblet) cells, and dry/scarred eyes; irreversible1. Impaired goblet cell number and function decreases the production ofmucus, and increases the chances of infectionb. U and J Shaped Curves: common for many nutrients; at high and low ends of vitamin status (toxicity and deficiency), a person will have the same risk of disease7. Reproductiona. Proper vitamin A is critical in development because of gene expressionb. Can be toxic at high dosesLecture 12Vitamin D1. Sourcesa. In food: found naturally as D2 (ergocalciferol)b. In animal products: found naturally is D3 (cholecalciferol)c. Synthesis in the skin:i. 7-dehydrocholesterol is absorbed in the skin; when in contract with UV light (sun) converted to pre-vitamin D3ii. Pre-vitamin D3 spontaneously converts to vitamin D3iii. Vitamin D3 diffuses into the blood2. Transport in Blooda. 25-OH D3 binds to D Binding Protein (DBP) after Vitamin D3 diffuses into the blood3. Activation of D3a. Liver hydroxylates vitamin D3 at the 25-carbon postion, and then it is transported to the kidney (bound to DBP)b. The kidney hydroxylates 25-OH D3 at the 1-carbon postion 1,25-dihydroxyl D3 is the active form of vitamin D3Lecture 13Vitamin D Cont. and Vitamins A/D in Gene Regulation1. Storage of Vitamin Da. Calcidiol: (25-hydroxy D3) is the most abundant form of vitamin D3 in the bodyb. Most of vitamin D is stored in the bloodc. Small skin and adipose reserves of cholecalciferold. Very little vitamin D remains in the liver2. Vitamin D Deficiencya. Rickets (in children): abnormal bone formation, especially in the legsb. Osteomalacia in adults3. Vitamin D Assessment: a. Serum levels of 25-OH D3b. Affected by Location/Latitude: In non-summer months, people living above the 37th parallel are at greater risk for vitamin D deficiency because the sun rays need to travel a longer distance to reach those areas (less UV light = decreased vitamin D synthesis in skin)4. Forms of Vitamins A and D Involved in Gene Regulationa. Vitamin A: all-trans or 9-cis retinoic acidb. Vitamin D: Calcitriol (1,25-(OH)2 D3)5. Mechanisms of Gene Regulationa. Vitamin A: Vitamin A binds to CRABP protein. Complex is transferred into the cell nucleus and binds to receptor on specific DNA sequence (RARE site). Retinoic acid can recruit an activator or a repressor to activate/inhibit transcriptionb. Vitamin D: Calcitriol binds to VDR protein. Complex is transferred into cell nucleus and binds to receptor on specific DNA sequence (VDRE site). Calcitriol can recruit an activator or repressor to activate/inhibit transcriptionLectures 14 and 15Calcium, Phosphorus, and Magnesium 1. Calciuma. Absorptioni. Transporter-Mediated: active transport via calcium transport 1 (TRPV6) into intestinal cell; once in cell calcium binds to calbindin to be shuttled through the cytoplasm and then is pumped into the blood via the ATP hydrolyzer pumpii. Paracellular Diffusion: transported through openings between cells (tight junctions are opened to allow calcium to pass) when calcium concentration ishighiii. Inhibitors: phytates, oxalates, fiber, increasing age, estrogen deficiency, divalent cations and minerals, and fatty acids via insoluble calcium soapsb. Calcium Concentrations: i. 99% of the body’s calcium is in the bone and teethii. Concentration of calcium is much lower in the cell than outside of the cell (~10,000 times lower)c. Hormone Regulationi. PTH: produced by chief cells of the parathyroid gland; functions to increase ECF Ca++ concentration1. In the kidney: increases synthesis of calcitriol (hydroxylation of 25-hydroxyl D3), increase of calcium reabsorption2. In the bone: stimulates the activity of osteoclasts (break down bone to release calcium into blood)ii. Calcitriol: synthesized in the kidney by 1-hydroxylase from 25-OH D3; functions to increase ECF calcium concentration1. In the small intestine: increases expression of calcium transporters, which increases absorption2. In the kidney: decreases synthesis of calcitriol when calcitriol levels in the blood are high (negative feedback mechanism, which prevents thekidney from producing too much)3. In the bone: stimulates the activity of osteoclasts4. In the parathyroid gland: inhibits PTH release (negative feedback mechanism, which prevents overly-high levels of calcium in the body)iii. Calcitonin: produced by parafollicular endocrine clear cells of the thyroid gland; functions to decrease ECF calcium contentration1. In the kidney: inhibits calcium and phosphorus reabsorption2. In the bone: inhibits osteoclast activity3. In the parathyroid gland: inhibits PTH secretion d. Calcium Regulation and Bonei. Active form of D3 (calcitriol) and PTH stimulate production of RANKL, which isproduced by osteoblasts. RANKL binds to the surface of osteoclasts to stimulate their maturation. When mature, osteoclasts will break down bone to release calcium