AA10 Purines

What are the main amino acid precursors for purine biosynthesis?

Glutamine, glycine, and aspartate.

: What molecule initiates de novo purine synthesis?

5-phosphoribosyl-1-pyrophosphate (PRPP).

What enzyme catalyzes the first committed step in purine synthesis?

Glutamine-PRPP amidotransferase.

What reaction does glutamine-PRPP amidotransferase catalyze?

Transfer of an amino group from glutamine to PRPP to form 5-phosphoribosylamine.

What are the energy requirements for adding glycine to the growing purine ring?

Requires ATP.

What is the final product of purine de novo synthesis?

Inosine monophosphate (IMP).

IMP can be converted into which two nucleotides?

AMP (adenosine monophosphate) and GMP (guanosine monophosphate).

What type of enzyme interconverts AMP, GMP, and their di- and triphosphate forms?

Nucleoside monophosphate and diphosphate kinases.

What is the function of nucleoside monophosphate kinase?

Transfers a phosphate from ATP to a nucleoside monophosphate to form a nucleoside diphosphate.

What is the function of nucleoside diphosphate kinase?

Converts nucleoside diphosphates (NDPs) into triphosphates (NTPs).

What condition results from excess uric acid accumulation?

Gout.

In gout, uric acid accumulates as crystals where?

In the joints, especially the big toe.

The overproduction of uric acid is the end result of which pathway?

Purine nucleotide catabolism.

What enzyme salvages free adenine into AMP?

Adenine phosphoribosyltransferase (APRT).

What enzyme salvages hypoxanthine and guanine?

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT).

Deficiency in HGPRT causes what disease?

Lesch-Nyhan syndrome.

What are symptoms of Lesch-Nyhan syndrome?

Neurological dysfunction, self-mutilation, and uric acid overproduction.

What enzyme converts ribonucleotides into deoxyribonucleotides?

Ribonucleotide reductase.

What cofactors are required by ribonucleotide reductase?

Thioredoxin or glutaredoxin and NADPH.

Which enzyme regenerates reduced thioredoxin using NADPH?

Thioredoxin reductase.

What are the three main one-carbon group transfer cofactors?

Biotin (CO₂), tetrahydrofolate (various oxidation states), and S-adenosylmethionine (methyl groups).

What are the end products of purine and pyrimidine degradation?

Purines → uric acid;

Pyrimidines → urea.

How is purine biosynthesis regulated?

Feedback inhibition by IMP, AMP, and GMP on earlier pathway enzymes.

What is the function of PRPP in nucleotide metabolism?

Acts as a ribose-phosphate donor in both de novo synthesis and salvage pathways.

What is the clinical significance of feedback inhibition in purine biosynthesis?

Prevents excessive accumulation of purine nucleotides and uric acid.

What chemotherapeutic agents target nucleotide synthesis?

Methotrexate and 5-fluorouracil (inhibit tetrahydrofolate-dependent reactions in nucleotide synthesis).

What is the biochemical effect of methotrexate?

Inhibits dihydrofolate reductase, blocking tetrahydrofolate regeneration and nucleotide synthesis.

What is the purpose of salvage pathways in purine metabolism?

To recycle free bases, saving energy by avoiding full de novo synthesis.

Which enzyme deficiency can cause gout due to overproduction of PRPP?

Partial HGPRT deficiency.

What enzyme deficiency leads to severe immunodeficiency due to toxic nucleotide accumulation?

Adenosine deaminase deficiency (ADA).

What regulates the balance between AMP and GMP synthesis from IMP?

Feedback inhibition—AMP inhibits its own synthesis branch and vice versa.

What is the key difference between purine and pyrimidine biosynthesis?

Purines are built directly onto PRPP,

while pyrimidine rings are synthesized first, then attached to PRPP.

What steps lead from IMP → AMP?

IMP + Aspartate + GTP → Adenylosuccinate, catalyzed by adenylosuccinate synthetase.

• Adenylosuccinate → AMP + Fumarate, catalyzed by adenylosuccinate lyase.

What is the energy source used to make AMP?

GTP.

What steps lead from IMP → GMP?

• IMP → XMP (xanthosine monophosphate), a redox step requiring NAD⁺.

  • XMP + Glutamine + ATP → GMP, catalyzed by GMP synthetase (also known as XMP-glutamine amidotransferase).

What is the energy source used to make GMP?

ATP.

How does AMP regulate purine synthesis?

AMP inhibits adenylosuccinate synthetase, preventing excess AMP formation.

How does GMP regulate purine synthesis?

GMP inhibits IMP dehydrogenase, preventing excess GMP formation.

How do AMP, GMP, and IMP regulate early steps?

High levels of these nucleotides inhibit PRPP → 5-phosphoribosylamine, slowing de novo synthesis.

What enzyme converts adenine to hypoxanthine?

Adenine deaminase (deamination reaction).