Nucleotide Metabolism- Brar

Question 1

What is the structure of nucleosides?

Answer 1

• Sugar + Base
• Linked thru an N-glycosidic linkage.
• Purines bond to the C1’ carbon of the sugar at their N9 atoms.
• Pyrimidines bond to the C1’ carbon of the sugar at their N1 atoms.

Question 2

What is the structure of nucleotides?

Answer 2

• Nucleoside + phosphate(s)

- Phosphate attached to the 5’ end thru esterification.

Question 3

How do you distinguish between nucleosides and nucleotides?

Answer 3

1. Nucleosides:
   •Purine nucleosides end in “-sine” (Adenosine, Guanosine)
   •Pyrimidine nucleosides end in “-dine” (Thymidine, Cytidine, Uridine)
2. Nucleotides:
   •Start with the nucleoside name from above and add “mono-”, “di-”, or “triphosphate” (Adenosine Monophosphate, Cytidine Triphosphate, Deoxythymidine Diphosphate)

Question 4

What molecules contribute to the structure of purines? What cofactors are required? What are the inhibitors and activators?

Answer 4

(5’-phophoribosyl-1-pyrophosphate (PRPP) → IMP)

1. Glutamine contributes N1 and N4.
2. Glycine contributes N2 and 2Cs
3. CO2 contributes C5
4. Aspartate contributes N6.
5. THF contributes C3 and C7 (Sulfa drugs and folic acid analogs inhibit THF synthesis)
6. Cofactors required: Mg2+, K+, Mn2+ and H2O.
7. 4 ATPs required.
8. Inhibitors: AMP, GMP and IMP.
9. Activators: PRPP (starting substrate)

Question 5

What molecules contribute to the structure of pyrimidines?

Answer 5

1. CO2 contributes 1 carbon.
2. Amide nitrogen (R-group) of glutamine contributes 1 nitrogen.
3. Aspartic acid contributes everything else (3Cs and 1N).

Question 6

What is mycophenolic acid? What does it do? What is is used for?

Answer 6

• Reversible uncompetitive inhibitor of inosine monophosphate dehydrogenase.
• Deprives rapidly proliferating T and B cells of key components of nucleic acids.
• This drug is used to prevent graft rejection.

Question 7

What is Adenosine deaminase (ADA) deficiency?

Answer 7

• This enzyme converts adenosine → inosine.
• Causes a type of severe combined immunodeficiency (SCID), involving T-cell and B-cell depletion.
• dATP accumulates in blood cells which inhibits DNA synthesis.
• Kids die before 2 years old.

Question 8

What is Gout?

Answer 8

• Characterized by hyperuricemia w/ recurrent attacks of acute arthritic joint inflammation, caused by deposition of monosodium urate crystals.
• Results from underexcretion of uric acid.
• Treatment w/ allopurinol inhibits xanthine oxidase resulting in accumulation of hypoxanthine and xanthine which are more soluble.