PROBLEM SET 18B. CYSTEINE AND MEHIONINE. THE METHYLATION CYCLE

Given:

a. Methionine acts catalytically in a wide variety of methylation reactions.

b. 5′-S-adenosylmetionine (SAM) is the proximal methylating agent for many methylation reactions.

c. The methylation cycle requires N5-methyltetrahydrofolic acid  and cob(I)alamin.



 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1. Write a general reaction for methylation using methionine as the donor. Predict the product formed from methionine.

2. What can you conclude from the answer to question 1 and the fact (given) that methionine acts catalytically in the methylation cycle?

3. Me-FH4 is formed from serine.  (See Section 15.4 of CBM). Show how this fits into the methylation cycle.

4. From the name alone, write the structure for 5′-adenosylmethionine.

5. Write a mechanism for the synthesis of SAM.

6. Write a general reaction for a methylation involving SAM.

7. Construct a methylation cycle based on your answers so far. What is missing?

8. Write a simple mechanism from conversion of adenosylhomocysteine to homocysteine.

9. Thioethers are not easily cleaved by hydrolysis. In fact, cleavage of adenosylhomocysteine requires both oxidation and reduction. Show how this occurs.

10. Update the methylation cycle you have written.

11. Methionine synthase, which is also called methyl-tetrahydrofolate-homocysteine methyl transferase, contains tightly bound cob(I)alamin.

Using the simplified structure (above), show how cob(I)alamin might works in the transfer of the methyl group from Me-FH4 to homocysteine.

12. Complete the methylation cycle. Include the enzymes and coenzymes.

 

 

Leave a Comment