BIOC 432 - Pyrimidines

What are the major pyrimidine bases?

Cytosine (C), Uracil (U), and Thymine (T).

In pyrimidine synthesis, is the base or the sugar assembled first?

The base (orotate) is synthesized first, then attached to ribose-5-phosphate

How does pyrimidine synthesis differ from purine synthesis?

In pyrimidine synthesis, the ring is built before attaching to PRPP; in purine synthesis, the ring is built on the ribose (PRPP).

Which enzyme is the key regulatory enzyme in pyrimidine synthesis?

Carbamoyl phosphate synthetase II (CPS II).

What activates CPS II allosterically?

PRPP (phosphoribosyl pyrophosphate).

What inhibits CPS II by feedback inhibition?

UTP (the end product).

What is the allosteric activator of ATCase (Aspartate Transcarbamoylase) in bacteria?

ATP (signals energy availability and need for nucleotides).

What inhibits ATCase (Aspartate Transcarbamoylase) in bacteria?

CTP (end-product feedback inhibition).

Which step is targeted by the anti-cancer drug 5-fluorouracil (5-FU)?

5-FU inhibits thymidylate synthase, blocking dTMP synthesis.

Why must pyrimidine degradation be functional for 5-FU to work safely?

To prevent toxic buildup of 5-FU and metabolites—dihydropyrimidine dehydrogenase (DPD) must degrade 5-FU properly.

What happens if 5-FU degradation fails (e.g., DPD deficiency)?

Severe tissue toxicity and neurological damage due to 5-FU accumulation.

Are pyrimidine degradation products water-soluble or excreted?

They are water-soluble and excreted in urine.

Where in the cell does pyrimidine synthesis occur?

In the cytosol.

What two enzymes together form the UMP synthase complex?

Orotate phosphoribosyltransferase and orotate decarboxylase.

In bacteria, what enzyme is the main regulatory control point?

Aspartate transcarbamoylase (ATCase).

What structural change occurs when ATCase is activated?

It shifts from the T (tense) state to the R (relaxed) state.

Why is pyrimidine synthesis a target for anti-cancer drugs?

Because rapidly dividing cancer cells require large amounts of nucleotides for DNA replication.

Draw the pathway for pyrimidine synthesis

D

Draw the pyrimidine salvage pathway

Draw the pyrimidine degradation pathway