Question | Answer |
Lecture 47 | Lipid Soluble Vitamins I |
Vitamin A is ___ soluble. | lipid |
Vitamin B is very complex and ___ soluble. | water |
Vitamin K is involved in ___. | coagulation |
Fat soluble vitamin deficiencies are most often found in ___ or ___. | liver cholestasis or fat malabsoprtion |
Fat soluble vitamins tend to be fat soluble due to repeating saturated or unsaturated ___ units. | isoprene |
Retinol | Form of vitamin A, hydroxyl group on the end |
Vitamin A cannot be ___ in the human body. | synthesized |
Sources of vitamin A are from ___ in plants or animals that have consumed plants. | β-carotene |
β-Carotene Dioxygenase | Catalyzes formation of retinaldehyde from β-carotene present in the intestinal mucosae, activated by bile salts |
Source of carotene are “___” vegetables. | “yellow” (I.e. carrots) |
Source of vitamin A esters is ___. | beef liver (also egg yolks and fish) |
Retinaldehyde Reductase | Catalyzes reduction of retinaldehyde to retinol, uses NADPH |
Retinaldehyde can be oxidized to ___ by a NAD/FAD-dependent oxidoreductase. | retinoic acid |
Retinal can be converted to ___, used in glycoprotein synthesis. | retinyl phosphate |
Retinal Isomerase | Catalyzes isomerization of trans-retinal to cis-retinal |
Cis-retinal combines with opsin to form ___. | rhodopsin |
Stimulation of rhodopsin causes conversion to trans-retinal with release of ___ and ___. | opsin and nerve impulse (for color/vision) |
Retinol-Binding Protein (RBP) | Responsible for plasma transport, also associated with transthyretin (TTR) |
Transthyretin (TTR) | Responsible for transporting thyroid hormones |
Cellular Retinoid-Binding Protein (CRBP) | CRBP I through IV, CBRP II involved in intestinal absorption |
Cellular Retinoic Acid Binding Protein (CRABP) | CRABP I & II involved in embryogenesis |
Nuclear Retinoid Receptors (RAR/RXR) | Nuclear TF’s found in the nucleus, “nicely behaved” TF’s (domains for vitamin A binding, dimeraztion, DNA binding, transcription activation) |
Nuclear Retinoid Receptors (Retinoic Acid Receptors) | RARα, RARβ, RARγ, RXRα, RXRβ, RXRγ |
RARE/RXRE (Retinoic Acid Response Elements) | Specific DNA nucleotide sequence which RAR/RXR binds to |
Acute Promyelocytic Leukemia | Translocation of chromosomes 15 & 17, fusion of RARα receptor gene to the PML gene defeating normal regulation, responds to retinoic acid (vitamin A) therapy |
Promyelocytic Leukemia (PML) | Responsible for promoting immature myeloid cells to differentiate into mature cells |
___ is expressed in connective tissue, skin, and embryo at critical development stages. | RARγ |
Cells dependent on vitamin A (retinol and retinoic acid) decrease ___. | keratinization |
Deficiency of vitamin A leads to increased keratinization in the ___, ___, and ___, and for proper function of ___. | skin, cornea, and trachea, immunocytes |
___ is a build of keratin and early sign of vitamin A deficiency. | Bitot’s spots |
Xeropthalmia | Dryness of the conjunctiva, usually a result of severe vitamin A deficiency |
Keratomalacia | Irreversible blindness, can be a result of prolonged xeropthalmia, most common cause of blindness in 3rd worlds |
Vitamin A is involved in transferrin ___. | synthesis |
Transferrin | Transports iron (Fe) to bone marrow |
Vitamin A/Transferrin deficiency: | microcytic hypochromic anemia, resembles Fe deficiency anemia, “Fe resistant”, consider lead poisoning/Pica |
Hypervitaminosis A | Only from vitamin A overdose and not carotene, liver damage (toxic to the liver)/hemorrhage/coma/death |
Teratogenesis | Relating to or causing malformations of an embryo |
Vitamin A Teratogenesis (13-cis-Retinoic Acid) | Associated with >20% rate of spontaneous abortions and birth defects in the first trimester |
Vitamin A Anti-Carcinogenic Properties | Decreased incidence of cancer, but cannot be reproduced by direct dietary supplements of vitamin A |
Role of vitamin D is to maintain ___ and ___. | plasma calcium and phosphorous concentrations |
Vitamin D enhances ___ and ___ absorption from the small intestine and mobilization from bone. | calcium and phosphate |
Dietary vitamin D3 (animals) and vitamin D2 (plants) are absorbed ___ into ___ then into the ___ via the lymph. | passively into micelles then into the chylomicrons |
Vitamin D3 and D2 bind ___ in the ___ and is stored. | D-binding protein (DBP) in the liver |
Photosynthesis of ___ can produce vitamin D3 in the skin. | 7-dehydroxycholesterol (provitamin D3) |
Vitamin D is released from the liver after ___. | 25-hydroxylation |
Assessment of patient vitamin D status is by ___ level. | 25-hydroxy vitamin D [25(OH)D3] |
In the kidney, 25(OH)D3 is hydroxylated by 1-α-hydroxylase to ___. | 1,25-dihydroxy vitamin D3 |
1,25-dihydroxy vitamin D3 is the ___ form. | active |
___ is the inactive form and cleared from the system. | 24,25-dihydroxy vitamin D3 |
Parathyroid gland senses ___ levels and secretes parathyroid hormone . | calcium |
PTH ___ the hydroxylation of 25(OH)D3 to 1,25(OH)D3. | stimulates/increases |
Short term calcium regulation by vitamin D is by ___ Ca2+ release from the bone. | increased |
Long term calcium regulation by vitamin D is by ___ Ca2+/K+ absorption in the gut. | increased |
Low Serum Calcium (PTH/1,25(OH)D3) | PTH stimulates 1,25(OH)D3 production and decrease calcium in urine, 1,25(OH)D3 increases dietary Ca2+/K+, and PTH & 1,25(OH)D3 immediately increase serum calcium from bone |
1,25(OH)D3 interacts with ___ receptors in target tissue. | nuclear |
Rapid action of 1,25(OH)D3 is through ___, ___, and ___. | intracellular calcium, phosphatidyl inositol, and cyclic GMP |
VDR codes for ___, a nuclear transcription factor. | vitamin D receptor |
VDR forms heterodimer with ___. | RXR |
VDR/RXR heterodimer binds to ___. | vitamin D responsive elements |
Target tissues of vitamin D are: | intestine (increase absorption), bone (increase mobilization), ubiquitous |
Type I Vitamin D Resistant Rickets | (Vitamin D Dependent Rickets), caused by 1-α-hydroxalase deficiency |
Type II Vitamin D Resistant Rickets | Caused by VDR deficiency |
Individuals with cholestatic liver disease have decreased ___. | bone mineralization |
High Serum Calcium (PTH) | Parathyroid senses hypercalcemia decreases PTH increases calcitonin, calcitonin increases urine calcium decreases mobilization of calcium from bone, decreased PTH inhibits 1,25(OH)D stimulates 24,25(OH)D synthesis, decreased 1,25(OH)D decreases absorption |
Bowed legs is ___ in children learning to walk. | normal |
Rickets can be treated with ___ supplement. | vitamin D |
Lack of sunlight can lead to ___. | Rickets (vitamin D deficiency) |
Excess Vitamin D | Produces hypercalcemia by excess absorption of dietary calcium and excess mobilization of calcium from bone, body responds by PTH mechanisms (calcitonin) |
Toxicity of Vitamin D | Only function of vitamin D is mineral homeostasis, intakes as low as 400 IU/d are adequate, intakes higher than 2000 IU/d are toxic, sun exposure is deleterious |
Vitamin D Intake | Recommended adult intake 200-600 IU/d up to 2000 IU/d, 10-15 min in peak summer sun can generate 20,000 IU, US approach is 50,000 IU/month |
Source of vitamin E is ___. | vegetable oil |
Vitamin E absorption requires ___, ___, ___, and ___. | bile salt, pancreatic lipases, mixed micelles, and chylomicrons |
Vitamin E is a ___ in lipid peroxyl radical chain reaction . | radical quencher |
Vitamin E forms ___ in the process of quenching the radical. | vitamin E radical |
If vitamin E is radicalized multiple times, the vitamin E is ___. | lost |
___ quenches vitamin E radicals, regenerating vitamin E. | Vitamin C |
Vitamin E deficiency leads to accumulative deficiency of ___ functions. | peripheral nerve |
α-Tocopherol Transfer Protein Deficiency | Isolated vitamin E deficiency leading to progressive neurological disorder |
Homozygous Hypobetalipoproteinemia | Defective apo B leading to fat malabsorption, vitamin E deficiency, retinitis pigmentosa (acquired), and progressive neurological disorder |
Abetalipoproteinemia | Defective microsomal triglyceride transfer protein leading to fat malabsorption, retinitis pigmentosa, and progressive neurologic disorder |