Purine & Pyrimidine Metabolism: Synthesis, Salvage, and Regulation

What is the starting material for purine synthesis?

Ribose-5-phosphate, which is converted to PRPP.

What is the first complete purine nucleotide produced in de novo synthesis?

IMP (inosine monophosphate).

What are the additional donors used in purine synthesis?

Glycine, glutamine, aspartate, CO₂, and N¹⁰-formyl-FH₄.

What is the first common nucleotide product of pyrimidine synthesis?

UMP (uridine monophosphate).

What are the major inputs for pyrimidine synthesis?

Glutamine, CO₂, and aspartate.

What is the construction strategy for purine synthesis?

The purine ring is built on ribose/PRPP.

What is the construction strategy for pyrimidine synthesis?

The pyrimidine ring is built first, then attached to ribose.

What enzyme converts ribose-5-phosphate to PRPP?

PRPP synthetase.

What activates PRPP synthetase?

Inorganic phosphate.

What inhibits PRPP synthetase?

Purine nucleotides.

What is the role of CPS II in pyrimidine synthesis?

CPS II catalyzes the formation of carbamoyl phosphate.

What are the two major salvage enzymes for purines?

HGPRT (Hypoxanthine-guanine phosphoribosyltransferase) and APRT (Adenine phosphoribosyltransferase).

What is the primary goal of purine salvage?

To save ATP by salvaging existing purine bases.

How does purine salvage minimize uric acid formation?

By converting free purine bases back into nucleotides, reducing degradation.

What is the major regulatory mechanism for purine and pyrimidine synthesis?

Feedback inhibition.

What purine degradation product can cause gout?

Uric acid/urate.

Which enzyme directly forms uric acid?

Xanthine oxidase.

What drug inhibits xanthine oxidase?

Allopurinol.

What is the effect of increased purine salvage on uric acid levels?

It decreases free purine bases, leading to less uric acid formation.

What is Lesch-Nyhan Syndrome associated with?

HGPRT deficiency leading to increased uric acid and neurologic impairment.

What is the first step in purine degradation?

AMP/GMP is converted to nucleosides.

What is the final product of purine degradation?

Uric acid.

What is the relationship between PRPP and nucleotide synthesis?

PRPP serves as an activated ribose donor for nucleotide synthesis.

What inhibits CPS II in pyrimidine synthesis?

UTP.

What activates CPS II in pyrimidine synthesis?

PRPP.

What is the consequence of HGPRT deficiency?

Increased uric acid levels due to decreased purine salvage.

What are the later products of purine synthesis?

AMP and GMP.

What are the later products of pyrimidine synthesis?

UTP, CTP, and TTP.

What is the significance of feedback inhibition in nucleotide synthesis?

It prevents overproduction of nucleotides when sufficient levels are present.