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89 Cards in this Set
- Front
- Back
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What are the fat soluble vitamins
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F, A, D, K
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In general, which vitamins are stored in the body?
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In general, fat soluble bu tnot water soluble vitamins are stored in they body, an exception is vitamin B12 a water soluble vitamin that can be stored
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where are water soluble vitamins absorbed
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Intestinal epithelial cells by transporters with or without binding proteins. They are released into the blod bound to proteins
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How are the fat soluble vitamins absorbed
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incorporated inot micelles with fat and taken up by intestinal epithelial cells. They are then assembled inot chylomicrons and transported to the cells for storage.
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How are the fat soluble vitamins released
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A-released into the blood bound to retinal, D-converted to 25-hydroxyvitamin D and released boudn to a-globin 25OH D. Stored K and E are distributed to other organs in VLDLs
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What are the four vitamins reqiured by multienzyme dehydrogense complexes
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-Thiamine pyrpophosphae, coenzyme A, FAD, and NAD
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what are the dietary sources of thiamine (B1)
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milk, fish, lean meats, fortified breads and cereals
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How is thiamine activated
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converted to thiamine pyrophosphate by Thaminepyrophosphate kinase
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What types of reactions require thiamine as a cofactor
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transketolase from the PPP and dehydrogenases like pyruvate DH and a-KG DH
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decribe thaimine deficiency
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beriberi, disease of nervous system w/ impaired sensory perception, weakness/pain of extremeties, edema, irregular heartbeat. Chronic deficiency= Wernike-Korsakoff's syndrome w/ confabulation and amnesia, associated w/ alcoholics
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describe thamine toxicity
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thamine is not toxic
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What are the dietary sources of Pantothenic acid (b5)
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meats, whole grains, broccoli, avocados
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HOw is pantothenic acid (B5) activated
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The active form is co-enzyme A. Pantothenic acid is the center of Co-enzyme A, it is also part of acy-carrier protein
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What types of reactions require pantothenic acid (B5)
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reactions with CoA complexes like AA/FA degradation/synthesis, TCA cycle
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Describe pantothenic acid deficiency
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rare, causes enterities, alopeica, dermatitis, and adrenal insufficiency
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describe pantothenic acid toxicity
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not toxic
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what are the sources of riboflavin
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milk, eggs, meat, fish, bananas
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What is the active form of riboflavin
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FMN and FAD, Riboflavin is phosphorylated by a kinase to form FMN, FMN is converted to FAD by addtion of an adenine group from ATP
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What type of reactions does riboflavin participate in
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FMN=ETC, FAD=TCA cycle, AA/FA degradation, NO synthesis
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Describe riboflavin deficiency
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Rare, sxs= sensitivity to sunlgith, cheliosis, glossitis, dermatitis
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describe riboflavin toxicity
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not toxic
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what are the sources of niacin (B3)
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meat, fish, milk, eggs, nuts
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How is niacin activated
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converted to NAD by a multistep process. Note that NAD can also be made from tryptophan but need 60 mg to make 1mg, the system requires multiple other vitamins, despite inefficiency can make 50% of daily intake
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What types of reactions use niacin?
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NAD is a cofactor of dehydrogenases in TCA and degradtion of CHO's, fats, AA's, and nucleic acids, NADH is an electron carrier, NADPH is used in synthesis reactions
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Describe niacin (or tryptophan) deficiency
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pellegra- Dermatitis, diarrhea, dementia, death.
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Describe niacin toxicity
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not deadly but pharmacological levels used to treat hyperlipidemia can lead to flushing
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What are the sources of biotin
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liver, legumes, dark leafy veggies, tomatoes, carrots
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How is biotin activated
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must be released from dietary proteins by proteases to biocytin (biotin+lysine), Bontinidase hydrlyzes the amide bond between biotin and lysine to release biotin. Biontin protein ligase then adds biotin to the lysine of new carboxylases
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Describe biotin deficiency
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Can also be caused by biotinidase deficiency, in infants leads to impaired growth and neuro problems, causes dermatitis and hair loss in adults. can be caused by consumption of raw egg whites due to binding with avidin
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What type of reactions is biotin invovled in
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Carboxylase rxns. Biotin binds the CO2 examples include pyruvate carboxylase and acetyl CoA carboxylase for lipid synthesis
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What are the sources of pyridoxine (B6)
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beans, nuts, legumes, meats, eggs, fish, whole grains, cereals
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How is pyrixodine (B6) activated
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Converted to PLP via phosphorylation by pyridoxal kinase and then action of pyridoxine phosphate oxidase (requires FMN)
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Which rxns require Pyridoxine (B6)
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PLP reacts with the a-amino group on AA's and forms an amide bond. Enzymes include aminotransferases and decarboxylases
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Describe pyridoxine deficiency
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rare, cheliosis, glossitis, peripheral neuropathy, irritability ,convulsions, pellegra like symptoms
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Describe pyridoxine toxicity
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neurological disorders
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What are the sources of folate
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beans, legumes, cirtrus fruit, dark leafy green veggies, whole grains, meat
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How is folate activated
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Converted from dietary polyglutamic folate to monoglutamic foalte in the intestine by folate hydrolase, released into the blood in complex with folate binding protein, dihydrofolate reductase coverts folate to THF in two steps usng NADPH
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What type of reactions is folate reqiured for
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transfer of one caronb units-nucleotide synthesis, DNA synthesis (dUMP to dTMP), synthesis of methionine form homocysteine, SAM synthesis (with B12) and SAM rxns
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Describe folate deficiency
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note also caused by B12 defieicny because it is required for methionine synthease reaciton. Sxs include intestinal atorphy, macrocytic anemia, NT defects, mouth sores, glossitis, elevated homocysteine=>CVD, cancer, alzheimer's
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What vitamin is deficient in the "folate trap"
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B12. If B12 is deficient, the methionine synthase rxn is inhibted and 5-Me-THF can't be made into THF, the folate is trapped 5-Me-THF and the foalte cycle stops
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What are the sources of cobalamin (B12)
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meat, shellfish, milk, eggs, note that vegans need to supp
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How is cobalamin (b12) activated?
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The vitamin is released from dietary proteins by the low pH of the stomach and binds intrinsic factor. IF mediates uptake into intestinal cells by binding a specific receptor. B12 is released from the intestine into the blood bound to transcobalamin
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which rxns does cobalamin (B12) participate in
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methionine synthase and methyl malonyl-CoA mutase (branched chain AA degradation and odd chain fatty acid degradation)
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Describe B12 defieincy
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same as folate, Sxs include intestinal atorphy, macrocytic anemia, NT defects, mouth sores, glossitis, elevated homocysteine=>CVD, cancer, alzheimer's
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How might perniciuos anemia, a deficiency of intrinsic factor cause a b12 deficiency
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IF is required for B12 absorption into intestinal cells. Note elderly people are prone to pernicious anemia because IF is synthesized at lwo rates and absopriton of nutrients is poor
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What are the sources of vitamin K
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liver, egg yolk, califlour, cabbage, bacteria in intestine
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How is vitamin K stored and released
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Incorporated into chylomicrons for transport from the intestine to liver where it is stored. The liver released vitamin K in VLDLs for transport to other tissues
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Describe the role of vitamin K in post-translational modificaiton of proteins
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y-glutamylcarboylase is vitamin K dependent. THis enzyme catalyes the additon of CO2 as carboxyl group onto the y-carbon of glutamate residures in the N-terminal region of proteins converting Glut to Gla. Vascular coagulation factors and other calcium bniding proteins in bone and intestine require this modification
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Discuss the role of vitamin K in blood clotting
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Calcium binds the two carboxyl groups on y-carboxylated Gla residues (a modification via a vitamin K dependent enzyme) the Ca bound Gla residues tether the coagulation proteins to the surface of activated cells, binding of vitamin K dependent ocagulation proenzymes to the surface of platelets accelerates and localizes clot formation
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How do drugs like dicoumarol and warfarin inhibit blood clotting
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these drugs inhibit recycling of vitamin K epoxide which in turn inhibts the post-translational modification of glutamate to y-carboxygutamate/ Gla. The non-ycarboxylated factors bind poorly to the platelet surface so coagulation is inhibited.
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Describe vitamin K deficiency
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common in newborns, given vitamin K IM after birth, in adutls rare unless they have problem with absportion
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what are the sources of vitamin C
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frutis and veggies
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What type of reactions is vitamin C involved in?
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prolyl hydroxylase and lysyl hydroxylase, required for the hydroxylation that allows collagen to cross link, acts as a reducing agent, reduction of Fe3+, recycling copper
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Describe vitamin C deficiency
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Scurvy, inability to crossl ink collagen and abnormal ECM sxs include fatiugre, aching bones and muslces, acne, bleeding gums, loose teeth, bruises, corkscrew hair, later=wekaness, oesteoporosis, poor wound healing, bleeding
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What are the sources of vitamin E
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vegetable oils, liver, eggs
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What type of reactions does vitamin e participate in
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Antioxidant, prevents non-enzymatic oxidation of PUFA's by ROS. protects RBCs from lysis, kept reduced by vitamin C
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Describe vitamin E deficiency
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premature infants and adults with absportion problems, fragility of RBCs
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describe vitamin E toxicity
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not toxic
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What are the sources of vitamin A as B-carotene
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green leafy veggies, carrots, sweet potatoes, red peppers
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What type of reactions does vitamin A as B-carotene participate in
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better antioxidant than other forms of vitamin a
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Describe vitamin a B-carotene toxicity
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not toxic but can deposite in fat tissues turning the skin yellow-orange, note the color of the sclera does not change (distinguish from jaundice)
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which factors in the blood clotting pathway are vitamin K dependent?
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VII, IX, X, and II, they are calcium binding protiens that are y-carboxylated in the N-terminal region
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what are the sources of vitamin a as retinyl esters
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eggs, meat, diary
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Describe how vitamin A as beta carotene is absorbed
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B-carotene enters the intestinal epithelial cells and is either directly incorporated into chylomicrons or oxidized and cleaved into two molecules of RAL by a monooxygenase. The RAL is the reduced to retinol. The retinol is then esterified with a fatty acid by LRAT and incorporated into chylomicrons. The chylomicrons distribute the retinol to the body. Retinol is stored in the liver as a retinyl ester.
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Explain how dietary retinol, in the form of retinyl esters, is absorbed.
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The retinyl esters are hydrolyzed in the extracellular space by REH and then taken up into intestinal epithelial cells. The retinol is then esterified with a fatty acid LRAT and incorporated into chylomicrons. Th chylomicrons distribute the retinol the the body. Retinol is stored in the liver as retinyl esters.
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Retinol is stored in the body as retinyl esters in the liver. How is this vitamin A from moblized to target tissue?
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The retinyl esters are hydrolyzed by a retinyl hydrolase to free all-trans-retinol. The retinol binds to RBP incomplex with TTR in the blood. At the target tissue, the complex binds to megalin.
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The retinal epithelial cells receive vitamin A from the blood in the form of all-trans-retinol. What form is the vitamin converted to and how is this done?
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all-trans-retinol is converted to 11-cis-retinal. The retinol is first esterified with a lipd b LRAT and then isomerized to 11-cis-retinol and the FA is hydroyltically cleaved. 11-cis-retinol is then oxidized t o11-cis retinal by a retinal dehydrogenase. 11-cis retinal can then be inserted into rod and cone disc membranes and used for vision
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Explain how rhodopsin is formed in the rods
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Rod opsin binds 11-cis-retinal and a Schiff base is formed between a lysine on the opsin and the aldehyde of 11-cis-retinal. The protein opsin is called rhodopsin upon binding of 11-cis-retinal
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Expalin how the cone pigments and opsin are able to absorb different wavelengths
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each of the proteins binds 11-cis-retinal in a differnt conformation due to different amino acids in the bindng pockets. The different conformations result inbsoprtion of light of different wavelengths
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Expalin the changes that occur to 11-cis-retinal and the signal transduction that constitutes the visual cycle
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Light changes 11-cis-retinal to the all trans form. The changes Rhodopsin to metarhodopsin II. Transducin binds to metarhodopsin II and is activated by an exchange of GTP for GDP. The exchanged dissociates transducin and the a-subunit binds and activates phosphodiesterase. Phosphodiesterase converts cGMP to GMP which closes the cGMP gated sodium channel and sends a visual signal to the brain.
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Explain how all-trans-retinal is recycled after the visual signal is sent to the brain
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All-trans-retinal is released from metarhodopsin forming opsin. The all-trans-retinal is reduced to the alcohol form and transported to the pigment cells back to 11-cis-retinal. 11-cis-retinal then binds to opsin in the rods to reform rhodopsin. The system is now ready to absorb light again
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Describe vitamin A deficiency
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Night blindness due to a decrease in the population of the rods with 11-cis-rhodopsin, w/ increasing severity Bitot's spot on sclera, xerophthalmia, keratomalacia, follicular hyperkeratosis, mild deficiency decreases ability to fight viral infections
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Vitamin A in the form of retinoic acid regulates gene expression. Explain how vitamin A derivatives are converted into this active form.
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Retinol is oxidized to retinal by retinol dehydrogenases and alcohol dehydorgenases (reversible). Retinal is irreversibly oxidized to retinoic acid (RA) by retinal dehydrogenase
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How is the toxicity of retinoids managed
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the retinoids are bound to carrier proteins like CRBP, CRABP, and RALBP
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Explain how retinoic acid stimulated gene expression in target cells (what form is it in, what does it bind to?)
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all-trans-RA is isomerized to 9-cis-RA. RAR binds either for and RXR binds only the cis form. RXR forms homodimers with itself and heterodimers with RAR. These dimers bind to RARE's in the promoter region of retinoic acid-regulated genes and simulate gene transcription. Note that RXR can form heterdimers with other nuclear receptors including VDR, THR, and PPAR
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How can vitamin A be used as a drug? What forms?
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all-trans-retinoic and 13-cis-retinoic are used to tx acene and promylocytic leukemia (note teratogenicity), all-trans-retinoic acid is used topically to Tx mild acne and wrinkes w/o toxic effects
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Vitamin A in the form of B-carotene is not toxic despite during the skin yellow. Retinol and retinoic acid however are toxic. What are the sxs of toxicity
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blurred vision, abdominal discomfort, pealing of skin, loss of hair, headahce, liver enlargement, bone deformities. Note that retinoic acid is toxic at much lower levels than retinol because retinol can be stored in the liver
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How is vitamin D obtained from the diet
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-D2, ergocalciferol from plants, -D3 cholecalciferol in animal products
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How is vitamin D obtained endogenously
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From 7-dehyrocholesterol, an intermediate of the cholesterol synthesis pathway, in the skin 7-dehydrocholesterol is converted to D3/ cholecalciferol by UV light
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What are good sources of vitamin D
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cheese, butter, margarine, fortified milk, fish, fortified cereal
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Explain how vitamin D is converted into the active form
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D2 or D3 is first hydroxylated at the 25 position by 25-(OH)D3 hydroxylase in the liver. It is then transported to the kidney and hydroxylated again to form 1,25 dihydoxyvitamin D
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How is the activation of vitamin D regulated
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The first reaction in the liver is not regulated. The second hydoxylation in the kidney is regulated. PTH and low phosphate stimulate hydroxylation in the first posiition, It is inhibited by active vitamin D a feedback mechanism
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How does vitamin D regulate gene expression
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in the active form 1,25 dihyroxy-cholecalciferol (D3) binds to VDR. VDR forms a heterodimer with RXR (bound to 9-cis-retinoic acid). The complex binds to VDRE in the promoter of vitamin D responsive genes and initiates gene transcprition
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What happens to PTH when calcium is low? How does this affect vitamin D metabolism
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At low Ca levels, PTH is increased. PTH stimulates the activation of vitamin D, retention of Ca in the kidney, and release of Ca from the bones into the blood
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What happens to PTH when calcium is high? What affects does this have on vitamin D metabolism
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High Ca decreases PTH, low PTH stimulates the release of Ca by the kidney into the urine, hydroxylation of vitamin D is also low
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How does high phosphate affect vitamin D metabolism
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High levels of phosphate inhibt basal and PTH simulated synthesis of active vitamin D
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How does low phosphate affect vitamin D synthesis
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Low phosphate lelves stimulate the formation of active vitamin D
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Describe vitamin D deficiency
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children-rickets, Adults-osteoporosis, osteomalacia, less severe= thyroid changes, cancer, CVD, cognitive impairment, Parkinson disease
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Describe vitamin D toxicity
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diarrhea, dermatitis, headache, nausea, anorexia, calcification of sof tissue, deacalcification of bones, kidney stones
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