PROBLEM SET 20-HISTIDINE

1.  The structure of histidine is:

 

 

 

Count the pi-electrons. What can you conclude about the imidazole ring?

 

2. The energy levels of the MOs of the imidazole ring are:

 

Based on this diagram, discuss two general types of reactions that might occur and predict which one is more likely.

Given:

a. The 2-amino group of histidine is removed by beta-elimination.

b. The second reaction of histidine catabolism involves addition of water to C4 of the imidazole ring.

3. Write a mechanism for removal  of the amino group.

a. Is PALP required?

b. Does the required enzyme exist?

c. What is the name of the product? of the enzyme?

 

4. Write a mechanism for nucleophilic addition of water  to C4 of urocanic acid

 

5. The product of the urocanate hydratase (urocanase) reaction can exist in several tautomeric forms. What are they?

 

6.  Urocanate hydratase has a tightly bound NAD+. Write two mechanisms that make use of the coenzyme.

 

7. Based on the mechanisms you wrote in question 7, predict the product of the next reaction.

8. Construct a mini-map showing the hydrolysis of N-formimidoyl glutamic acid. Look up the enzymes required for the reactions you have predicted and add them to your minimap.

9. What does your map tell you about histidine metabolism in general.

10. N10-formyltetramydrofolic acid can be oxidized. Predict the product, then look for the enzyme.

11. Using abbreviated  structures,  show how N-formyltetrahydrofolate is converted  to N-methyltetrahydrofolate.

13. Construct a map for histidine catabolism. Include enzymes and coenzymes.

 

 

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