Purine Nucleotide Synthesis Quiz

Questions and Answers

What is the role of 5-Phosphoribosyl-1-pyrophosphate (PRPP) in purine synthesis?

It is an activated form of ribose. (correct)

It serves as an energy source.

It acts only as a phosphate donor.

It is essential for the activation of sulfonamides.

Which enzyme is responsible for the synthesis of 5-Phosphoribosyl-1-pyrophosphate?

Ribonucleotide reductase

PRPP synthetase (correct)

Inosine monophosphate dehydrogenase

Hypoxanthine guanine phosphoribosyltransferase

Which compound is required as a one-carbon donor in the synthesis of inosine monophosphate?

Dihydrofolate

Methyltetrahydrofolate

N10-formyltetrahydrofolate (correct)

Tetrahydrofolate

What type of inhibition is PRPP synthetase subject to?

End product inhibition by purine nucleotides Signup and view all the answers

What is the primary function of synthetic inhibitors of purine synthesis, such as sulfonamides?

To inhibit the growth of rapidly dividing microorganisms Signup and view all the answers

What is a consequence of the lack of the pyrimidine salvage pathway?

Increased PRPP levels Signup and view all the answers

Which enzyme step is indicated as a regulated step in purine synthesis?

Glutamine:phosphoribosylpyrophosphate amidotransferase Signup and view all the answers

What metabolic issue is associated with Lesch-Nyhan syndrome?

Increased degradation of purines Signup and view all the answers

Which condition is frequently a result of hyperuricemia in patients with Lesch-Nyhan syndrome?

Gouty arthritis Signup and view all the answers

What biochemical effect results from increased de novo purine synthesis?

Increased uric acid levels Signup and view all the answers

What primary function do deoxyribonucleotides serve in cellular processes?

Formation of DNA during replication Signup and view all the answers

What role does dATP play in the regulation of enzyme activity?

It inhibits the overall catalytic activity of the enzyme. Signup and view all the answers

Which of the following statements best describes the allosteric sites on the enzyme?

They regulate the enzyme's activity without being involved in catalysis. Signup and view all the answers

What is the primary effect of binding dATP to the activity sites of the enzyme?

It inhibits further production of nucleoside diphosphates. Signup and view all the answers

Which of the following best describes nucleotide metabolism in the context of DNA synthesis?

It maintains a balanced supply of deoxyribonucleotides. Signup and view all the answers

Which of the following statements regarding enzyme regulation is true?

Regulation complexity varies with different enzymes. Signup and view all the answers

What happens to the synthesis of nucleoside diphosphates when dATP binds to the allosteric sites?

Synthesis is inhibited due to decreased enzyme activity. Signup and view all the answers

Which factor is NOT a characteristic of the enzyme's activity sites?

They only function at a specific pH. Signup and view all the answers

What role does adenylate kinase play in the body?

It maintains equilibrium among adenine nucleotides like ATP, ADP, and AMP. Signup and view all the answers

Which molecule serves as an energy source for the synthesis of AMP?

Guanosine triphosphate (GTP) Signup and view all the answers

What is the first reaction in the salvage pathway of purines inhibited by?

The end product of that pathway Signup and view all the answers

How does the body respond when both AMP and GMP are present in adequate amounts?

It turns off the de novo pathway at the amidotransferase step. Signup and view all the answers

Which enzyme is responsible for converting hypoxanthine and guanine to nucleotides in purine salvage?

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) Signup and view all the answers

What is the primary substrate specificity of nucleoside diphosphate kinase?

It interconverts nucleoside diphosphates and triphosphates. Signup and view all the answers

What inhibits the synthesis of GMP from IMP?

The end product of the GMP synthesis pathway Signup and view all the answers

Which of the following statements about purine metabolism is true?

GMP synthesis requires ATP, whereas AMP synthesis requires GTP. Signup and view all the answers

What must happen to thioredoxin for it to continue functioning effectively?

It must be converted back to its reduced form. Signup and view all the answers

What provides the necessary reducing equivalents for the regeneration of reduced thioredoxin?

NADPH + H+ Signup and view all the answers

Which enzyme is primarily responsible for the degradation of purine nucleotides to free bases inside the intestinal mucosal cells?

Specific nucleotidases Signup and view all the answers

Where does the degradation of purine nucleotides from de novo synthesis primarily occur?

In the liver Signup and view all the answers

What is the final product of purine nucleotide degradation in the intestines?

Uric acid Signup and view all the answers

Which pathway involves the conversion of hypoxanthine to xanthine?

Oxidation pathway Signup and view all the answers

What is the role of thioredoxin reductase in the context of thioredoxin?

Regenerates thioredoxin to its reduced form. Signup and view all the answers

What occurs to purine nucleotides after they are hydrolyzed to nucleotides in the small intestine?

They are progressively degraded to free bases. Signup and view all the answers

Study Notes

Synthesis of Inosine Monophosphate

Inosine monophosphate (IMP) serves as a parent purine nucleotide, crucial for the synthesis of adenine and guanine nucleotides.

Synthesis of 5-Phosphoribosyl-1-Pyrophosphate (PRPP)

PRPP is an "activated pentose" and plays a role in the synthesis and salvage of purines and pyrimidines.
Synthesized by PRPP synthetase, an X-linked enzyme activated by inorganic phosphate.
End product inhibition is exerted by purine nucleotides.
PRPP has a ribose sugar moiety; thus, its synthesis leads to ribonucleotides.

Synthetic Inhibitors of Purine Synthesis

Synthetic inhibitors, such as sulfonamides, are designed to hinder the growth of rapidly dividing microorganisms without affecting human cells.
Adenylate kinase, prominent in the liver and muscle, facilitates the equilibrium of adenine nucleotides (AMP, ADP, ATP).
Nucleoside diphosphates (NDPs) and triphosphates (NTPs) are interconverted by nucleoside diphosphate kinase, which has broad substrate specificity.

Synthesis of Adenosine and Guanosine Monophosphate

Conversion of IMP to AMP or GMP occurs through energy-requiring, two-step pathways.
Synthesis of AMP utilizes GTP, while GMP synthesis uses ATP.

Salvage Pathways for Purines

Salvage pathways offer a mechanism to divert IMP for synthesizing the less abundant purine.
Two enzymes enable salvage: adenine phosphoribosyltransferase (APRT) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT).
Adequate AMP and GMP levels inhibit de novo purine synthesis, specifically at the amidotransferase step.

Consequences of Impaired Salvage Pathway

Lack of salvage pathways leads to increased PRPP levels and decreased levels of IMP and GMP.
Results in more purine synthesis and degradation, causing hyperuricemia, as seen in Lesch-Nyhan syndrome.
Symptoms include uric acid kidney stones (urolithiasis) and joint urate crystal deposition (gouty arthritis).

Regulation of Deoxyribonucleotide Synthesis

Ribonucleotide reductase maintains a balanced supply of deoxyribonucleotides for DNA synthesis.
Complex regulation involves allosteric sites that inhibit enzyme activity when dATP binds, preventing further reduction of nucleoside diphosphates.

Regeneration of Reduced Thioredoxin

Dietary nucleic acids degrade in the small intestine through pancreatic enzymes, yielding nucleotides.
Thioredoxin must return to its reduced form, with NADPH + H+ providing necessary reducing equivalents through thioredoxin reductase.
Degradation in the liver leads to the release of free bases, which are salvaged by peripheral tissues.

Oxidation of Hypoxanthine

Hypoxanthine undergoes oxidation by xanthine oxidase, converting it to xanthine as part of nucleotide metabolism.

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Description

Test your knowledge on the synthesis of inosine monophosphate and 5-phosphoribosyl-1-pyrophosphate. This quiz also covers synthetic inhibitors of purine synthesis and the role of enzymes involved in nucleotide interconversion. Challenge yourself on this important biochemical topic!