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Biochemistry Nucleotide Metabolism Part 2
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Biochemistry Nucleotide Metabolism Part 2

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Questions and Answers

What is the effect of an X-linked PRPP synthetase mutation on purine metabolism?

  • Increased salvage of guanine
  • Decreased sensitivity to purine nucleotides (correct)
  • Decreased Vmax for PRPP production
  • Increased production of hypoxanthine

    • Which condition is characterized by hyperuricemia due to decreased salvage of hypoxanthine and guanine?

  • Lesch-Nyhan Syndrome (correct)
  • Gout
  • Secondary Hyperuricemia
  • ADA deficiency

    • Which of the following conditions leads to increased availability of purine in the body?

  • Gout
  • Lesch-Nyhan Syndrome
  • ADA deficiency
  • Myeloproliferative disorders (correct)

    • What role does PRPP play in nucleotide metabolism?

    <p>Increases purine production</p> Signup and view all the answers

    Which metabolic event leads to elevated levels of plasma uric acid?

    <p>Increased PRPP levels</p> Signup and view all the answers

    Which of the following is NOT associated with the degradation of purine nucleotides?

    <p>Pyrimidine synthesis</p> Signup and view all the answers

    What is the role of carbamoyl phosphate in nucleotide metabolism?

    <p>It contributes to the synthesis of pyrimidines</p> Signup and view all the answers

    Which factor does NOT contribute to secondary hyperuricemia?

    <p>Decreased PRPP availability</p> Signup and view all the answers

    Which enzyme is responsible for the synthesis of carbamoyl phosphate from glutamine and CO2?

    <p>Carbamoyl phosphate synthetase II</p> Signup and view all the answers

    What effect does UTP have on carbamoyl phosphate synthetase II?

    <p>It inhibits the enzyme</p> Signup and view all the answers

    Which precursor is responsible for the formation of urea?

    <p>Carbamoyl phosphate</p> Signup and view all the answers

    What is the role of aspartate transcarbamoylase in pyrimidine metabolism?

    <p>Catalyzes the conversion of carbamoyl aspartate to dihydroorotate</p> Signup and view all the answers

    Which enzyme is solely found in the inner mitochondrial membrane and is involved in UTP synthesis?

    <p>Dihydroorotate dehydrogenase</p> Signup and view all the answers

    Which process is facilitated by the multifunctional CAD synthetase?

    <p>Formation of carbamoyl phosphate, carbamoylaspartate, and dihydroorotate</p> Signup and view all the answers

    What is the result of a defect in ornithine transcarbamylase?

    <p>Increased synthesis of pyrimidines</p> Signup and view all the answers

    Which compound serves as the nitrogen source in the synthesis of carbamoyl phosphate?

    <p>Glutamine</p> Signup and view all the answers

    What is the role of thymidylate synthase in the conversion of dUMP to dTMP?

    <p>It catalyzes the methylation of dUMP.</p> Signup and view all the answers

    How does 5-fluorouracil function as a therapeutic agent?

    <p>It permanently binds to thymidylate synthase, acting as a suicide inhibitor.</p> Signup and view all the answers

    What is the effect of Methotrexate on nucleotide metabolism?

    <p>It inhibits DNA synthesis by decreasing THF supply.</p> Signup and view all the answers

    What are the soluble products formed from the degradation of pyrimidine nucleotides?

    <p>Beta-alanine, beta-aminoisobutyrate, NH3, and CO2</p> Signup and view all the answers

    What is the primary mechanism of action of trimethoprim?

    <p>It potently inhibits bacterial dihydrofolate reductase.</p> Signup and view all the answers

    What is the role of nucleotide kinases in nucleotide metabolism?

    <p>They phosphorylate nucleosides to form nucleotides using ATP.</p> Signup and view all the answers

    How does uridine function in the treatment of hereditary orotic aciduria?

    <p>It acts as a substitute for defective enzymes in pyrimidine metabolism.</p> Signup and view all the answers

    In the synthesis of TMP, what does tetrahydrofolate (THF) contribute?

    <p>One carbon unit and two hydrogen atoms.</p> Signup and view all the answers

    What is the primary consequence of elevated dATP levels in lymphocytes?

    <p>Promotion of lymphocyte apoptosis</p> Signup and view all the answers

    Which component is released by orotate phosphoribosyltransferase during pyrimidine nucleotide formation?

    <p>Pyrophosphate</p> Signup and view all the answers

    What genetic condition results in a decrease of T, B, and NK cells due to a defect in purine metabolism?

    <p>Severe combined immunodeficiency disease</p> Signup and view all the answers

    Which of the following is involved in converting orotidine 5’-monophosphate (OMP) to uridine monophosphate (UMP)?

    <p>Orotidylate decarboxylase</p> Signup and view all the answers

    What is the fate of cells when ribonucleotide reductase activity is inhibited due to high dATP levels?

    <p>Developmental arrest and apoptosis</p> Signup and view all the answers

    Which amino acid is an integral source for pyrimidine ring synthesis?

    <p>Glutamine</p> Signup and view all the answers

    What is the primary function of adenosine deaminase (ADA) in nucleotide metabolism?

    <p>Degradation of adenosine</p> Signup and view all the answers

    Which treatment option is effective for severe combined immunodeficiency disease?

    <p>Bone marrow transplant</p> Signup and view all the answers

    What is a less common cause of gout aside from hyperuricemia?

    <p>Purine nucleoside phosphorylase deficiency</p> Signup and view all the answers

    Which enzyme is responsible for the synthesis of deoxyribonucleotide from ribonucleotide?

    <p>Ribonucleotide reductase</p> Signup and view all the answers

    What is the primary cause of gout?

    <p>Overproduction or underexcretion of uric acid</p> Signup and view all the answers

    Which statement correctly describes the relationship between diet and gout severity?

    <p>Low-fat dairy products decrease the risk of gout</p> Signup and view all the answers

    What diagnostic procedure is used to confirm the presence of monosodium urate crystals in gout?

    <p>Aspiration and examination of synovial fluid</p> Signup and view all the answers

    What is the role of colchicine in the treatment of gout?

    <p>It prevents neutrophil movement to the affected area</p> Signup and view all the answers

    Which drug can be used to lower uric acid levels in patients considered overexcretors?

    <p>Allopurinol</p> Signup and view all the answers

    What is chronic tophaceous gout characterized by?

    <p>Formation of large, painful deposits of urate crystals</p> Signup and view all the answers

    What is the function of uricosuric agents in gout treatment?

    <p>Enhance the renal excretion of uric acid</p> Signup and view all the answers

    Which lifestyle change is likely to lower the risk of gout?

    <p>Regular exercise and weight management</p> Signup and view all the answers

    What characterizes urate crystals when viewed under polarized light microscopy?

    <p>They show an apple-green birefringence</p> Signup and view all the answers

    Which condition can occur as a result of chronic gout if not properly managed?

    <p>Chronic kidney disease from urate nephropathy</p> Signup and view all the answers

    Study Notes

    Nucleotide Metabolism Overview

    • Mutations in X-linked PRPP synthetase lead to increased production of PRPP.
    • Higher PRPP levels result in enhanced purine nucleotide production and elevated plasma uric acid levels.

    Purine Nucleotide Degradation

    • Gout characterized by hyperuricemia, leading to gouty arthritis and soft tissue deposits.
    • Gout results from either overproduction or underexcretion of uric acid, presenting with acute inflammatory responses.
    • Uric acid typically deposits in joints, soft tissues, and kidneys.
    • Diagnosis involves aspiration of synovial fluid to identify monosodium urate crystals through polarized light microscopy.

    Diseases Associated with Purine Degradation

    • Lesch-Nyhan syndrome leads to hyperuricemia due to decreased salvage pathways and increased PRPP.
    • Secondary hyperuricemia arises from myeloproliferative disorders, chemotherapy, or high cellular turnover.

    Treatment for Gout

    • Anti-inflammatory medications like colchicine, prednisone, and indomethacin are used for symptom relief.
    • Uricosuric agents (e.g., probenecid, sulfinpyrazone) help lower uric acid levels.
    • Allopurinol inhibits uric acid synthesis for hyperuricemia cases.

    Overproduction of Uric Acid

    • Primary hyperuricemia can be idiopathic, resulting in high dATP levels.
    • Increased dATP inhibits ribonucleotide reductase, affecting DNA synthesis and lymphocyte development.

    Severe Combined Immunodeficiency Disease

    • Autosomal recessive disorder resulting in reduced T, B, and NK cells due to ADA deficiency.
    • Treatment options include bone marrow transplant and enzyme replacement therapy.

    Pyrimidine Nucleotide Synthesis and Degradation

    • Pyrimidine rings are synthesized before attachment to ribose-5-phosphate from PRPP.
    • Key components for pyrimidine synthesis include glutamine, aspartic acid, and CO2.

    Synthesis of Carbamoyl Phosphate

    • Involves the conversion of glutamine and CO2 regulated by carbamoyl phosphate synthetase II (CPS II).
    • CPS II activity is inhibited by UTP but activated by PRPP.

    Synthesis of Orotic Acid

    • Formed from carbamoylaspartate through aspartate transcarbamoylase and dihydroorotase.
    • Dihydroorotate dehydrogenase catalyzes oxidation to orotic acid, located in the inner mitochondrial membrane.

    Synthesis of UTP and CTP

    • CTP is produced by amination of UTP, using glutamine as a nitrogen source.
    • UMP synthetase pathways convert orotic acid to UMP, facilitating nucleic acid synthesis.

    Synthesis of Thymidine Monophosphate (TMP)

    • TMP is synthesized from dUMP by thymidylate synthase, inhibited by fluorouracil.
    • N5,N10-methylene tetrahydrofolate is crucial for adding methyl groups during TMP synthesis.

    Salvage Pathway for Pyrimidines

    • Nucleotide kinases phosphorylate nucleosides to nucleotides using ATP.
    • Uridine can be therapeutically administered in hereditary orotic aciduria cases.

    Degradation of Pyrimidine Nucleotides

    • Pyrimidines are degraded into soluble products, including β-alanine, β-aminoisobutyrate, ammonia (NH3), and carbon dioxide (CO2).

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    Description

    This quiz focuses on the degradation of purine nucleotides and the associated diseases. It explores the impact of X-linked PRPP synthetase mutation on purine production and plasma uric acid levels. Perfect for understanding complex biochemical pathways.

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