Nucleotide metabolism

What are the 2 methods of nucleotide metabolism?

De novo pathway

• Nucleotides assembled from precursors including activated ribose, amino acids, ATP, co2, etc.

Salvage pathway

• Nucleotides recovered from activated ribose and a base

What is a nucleoside?

Nucleoside - purine or pyrimidine attached to a ribose sugar, NOT INCLUDING THE PHOSPHATE

Nucleotide - phosphate ester form of nucleoside (INCLUDES PHOSPHATE)

Label each nitrogenous base

3 steps of pyrimidine synthesis

1. synthesis of carbamoyl phosphate

2. carbamoyl phosphate reacts with aspartate to make a ring

3. ribose phosphate is added using PRPP

What is carbamoyl phosphate made from? What enzyme is needed?

Bicarbonate and ammonia, enzyme is CPSII

What proteins catalyze interconversion of di and triphosphates?

Nucleoside diphosphate kinases

What are the two major pyrimidine nucleotides?

CMP and UMP

How is thymine made?

DNA degradation and salvage pathway

Viral thymidine kinase

A good target for medicines because it is different from mammal thymidine kinase

How does acyclovir help treat herpes simplex virus infection?

The drug competes with dGTP for DNA polymerase and terminates chain elongation

What is a purine ring assembled on?

Ribose phosphate

What 3 amino acids are precursors to purines?

glycine, glutamine, and aspartate

What is the committed step of purine formation?

Formation of 5-phosphoribosyl 1-amine from PRPP and ammonia by amidotransferase

Inosinate is the precursor for which two nucleotides?

AMP and GMP

How is deoxyribose made from ribose?

2’ hydroxyl group of carbon is replaced with an H

Which enzyme adds a methyl group to dUMP to make thymidylate?

Thymidylate synthase

What inhibits thymidylate synthase? What condition is it used for?

Aminopterin and methotrexate, as well as fluorouracil inhibit dihydrofolate reductase, which stops thymidylate synthesis as a target for cancer cell inhibition