MEDCHEM 562 Fall 2013 Vitamin Problem Set 1: Deficiency

Transcription

1 1) Complete the table: MEDCHEM 562 Fall 2013 Vitamin Problem Set 1: Vitamin Function / Uses Deficiency States Toxicities Daily Value Upper Limit A D E K

2 2) Complete the metabolic pathway shown below: Retinyl esters (all trans retinyl palmitate) Retinol 11-cis retinol Opsin (,) 11-cis-retinal dehydrogenase hv () Opsin all-trans-retinoic acid CYP26A1 CYP26B1 CYP26C1 and a) Which fat-soluble vitamin is this pathway related to b) Which sense (hearing, sight, smell, taste, or touch) does the pathway play a role in Name a symptom associated with a deficiency in the vitamin in part A and the sense affected by this pathway c) ATRA binds to which heterodimeric receptor to control growth and development

3 3) Acitretin is a vitamin A related drug. The structure is shown below: O OH O a) What is the half-life of the Acitretin b) Acitretin can be converted to what other drug in patients who consume large amounts of alcohol. What is this drug Draw the structure of this drug. What is its half-life c) How can the drug in part b be converted back to acitretin 4) The structure of β-carotene is shown below:

4 a) β-carotene is cleaved to yield how many moles of retinal Circle the portion that is important for Vitamin A activity. Indicate on the structure where the bond cleavage takes place. b) A patient is worried about hypervitaminosis A because he/she eats a diet high in carrots. Should he/she be concerned by vitamin A produced by the cleavage of β-carotene (found in carrots) Why or why not 5) Question 5 Enzyme: Location: Enzyme: Location: HO HO HO Name: Cholecalciferol Name: Name: a) Cholecalciferol is shown on the far left. Which fat-soluble vitamin is this b) Cholecalciferol is hydroxylated twice by P450s to yield the active form of this vitamin. i. Draw in the hydroxyl groups on the structures above in each step. ii. Indicate which CYP carries out each hydroxylation and the location (which organ) it takes place in. iii. Finally, provide a name for each molecule (there are multiple names for each!).

5 6) Vitamin D and parathyroid hormone (PTH) have important roles in metabolic bone disease. a) Metabolic bone disease typically happens as a result of failure in which organ b) Metabolic bone disease is associated with deficiency of which mineral in the bones c) Describe how PTH interacts with bones, the failed organ in part a, and the mineral in part b. Provide reasoning for how this can cause metabolic bone disease. d) What can be prescribed to patients to help patients who have failure in the organ from part a 7) Menadione is shown below: O O

6 a) Menadione is also known as vitamin. b) Is menadione active If so, identify the portions that contribute to its activity. If not, what modification needs to be done for it to become active 8) What is a potential health risk associated with prescribing warfarin at high doses How does this occur Which enzyme does warfarin inhibit to accomplish its therapeutic effect 9) A patient who recently finished taking his/her prescription of antibiotics might be expected to have higher or lower amounts of gut bacteria (circle one). Which specific vitamin s production can be altered by changes in gut flora Is this vitamin active or inactive Based on your previous answer, would the vitamin production increase or decrease as a result 10) Identify two structural features of vitamin E that are essential for its biological activity.

7 11) α-tocopherol is the most important form of vitamin E. One electron oxidation of α- tocopherol leads to resonance stabilization of the radical shown below. a) The radical can interact with which vitamin to regenerate Vitamin E b) Show diagrammatically how this occurs. c) Donation of H! (given off in the one electron oxidation mentioned above) can neutralize what type of radical discussed in class

8 12) Some multiple-choice questions below. Only one answer is correct. Copper and zinc intake would be important for high activity of what important enzyme that helps protect against free radical damage a) superoxide dismutase b) glutathione reductase c) peroxidase d) catalase Riboflavin helps to reduce the damage caused by free radical reactions because; a) glutathione peroxidase requires NADPH, b) glutathione reductase requires NADPH, c) glutathione peroxidase requires FAD, d) glutathione reductase requires FAD. Selenium has an important antioxidant role because it is a constituent of: a) glucose-6-phosphate dehydrogenase, b) superoxide dismutase, c) glutathione reductase, d) glutathione peroxidase. 13) Identify the three major (general) causes of vitamin deficiency and give a specific example of a group of people at risk for each one.