Biochemistry Nucleotide Metabolism Part 2
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Questions and Answers

What is one of the main functions of oxypurinol in the context of uric acid management?

  • It promotes the excretion of uric acid
  • It enhances the production of uric acid
  • It inhibits the enzyme xanthine oxidase (correct)
  • It increases the absorption of hypoxanthine

    • Which condition might result in underexcretion of uric acid due to environmental factors?

  • Hypotension
  • Chronic kidney disease
  • Congestive heart failure
  • Saturnine gout from lead exposure (correct)

    • What effect does lactic acidosis have on uric acid excretion?

  • It inhibits the production of lactate
  • It alters the availability of renal transporters for urate (correct)
  • It increases the renal clearance of uric acid
  • It decreases competition between lactate and urate for renal transport

    • In cases of purine metabolism issues, what role does hypoxanthine have concerning uric acid production?

    <p>It directly produces uric acid through de novo synthesis</p> Signup and view all the answers

    What is the primary characteristic of primary underexcretion of uric acid?

    <p>It is caused by as-yet-unidentified inherent excretory defects</p> Signup and view all the answers

    What is the primary consequence of increased levels of PRPP due to X-linked PRPP synthetase mutation?

    <p>Elevated levels of plasma uric acid</p> Signup and view all the answers

    In Lesch-Nyhan syndrome, which metabolic change primarily contributes to hyperuricemia?

    <p>Decreased salvage of hypoxanthine and guanine</p> Signup and view all the answers

    What is a characteristic feature of secondary hyperuricemia?

    <p>It involves increased availability of purine nucleotides.</p> Signup and view all the answers

    Which enzyme is directly involved in the synthesis of orotic acid during pyrimidine metabolism?

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

    What effect does a lower Km for ribose 5-phosphate have on PRPP synthetase activity?

    <p>It increases PRPP production efficiency.</p> Signup and view all the answers

    Which of the following is NOT a result of elevated PRPP levels?

    <p>Decreased uric acid production</p> Signup and view all the answers

    What is one of the key effects of chemotherapy on purine nucleotide metabolism?

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

    How does ADA deficiency affect nucleotide metabolism?

    <p>It results in accumulation of toxic metabolites and increased uric acid.</p> Signup and view all the answers

    Which condition is characterized by an accumulation of adenosine due to ADA deficiency?

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

    What is the result of an increase in dATP levels within cells?

    <p>Inhibition of deoxyribose-containing nucleotide production</p> Signup and view all the answers

    Which enzyme is responsible for converting orotidine 5’-monophosphate (OMP) to uridine monophosphate (UMP)?

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

    What genetic defect is associated with orotic aciduria?

    <p>Deficiency of one or both activities of UMP synthase</p> Signup and view all the answers

    What primary contributor to nucleotide synthesis is derived from ribose-5-phosphate?

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

    What is the fate of lymphocytes in the most severe form of severe combined immunodeficiency disease?

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

    Which pyrimidine nucleotide is formed after the completion of the pyrimidine ring?

    <p>Uridine monophosphate (UMP)</p> Signup and view all the answers

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

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

    What is one common outcome of purine nucleoside phosphorylase deficiency?

    <p>Less severe complications than ADA deficiency</p> Signup and view all the answers

    What role does UTP play in the regulation of carbamoyl phosphate synthetase II?

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

    Which factor contributes directly to the synthesis of the pyrimidine ring?

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

    Which statement is true regarding the synthesis of orotic acid?

    <p>Aspartate transcarbamoylase catalyzes the initial step of orotic acid synthesis.</p> Signup and view all the answers

    What treatment option is generally considered for individuals with severe combined immunodeficiency disease?

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

    Which enzyme is responsible for the amination of UTP to form CTP?

    <p>CTP synthetase</p> Signup and view all the answers

    What is the consequence of a defect in ornithine transcarbamylase?

    <p>It promotes pyrimidine synthesis.</p> Signup and view all the answers

    Where is dihydroorotate dehydrogenase located within the cell?

    <p>Inner mitochondrial membrane</p> Signup and view all the answers

    What is the final product of the enzymatic conversion of dCDP?

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

    Which combination of enzymes is associated with the multifunctional peptide domain CAD?

    <p>CPS II, aspartate transcarbamoylase, and dihydroorotase</p> Signup and view all the answers

    What is the role of thymidylate synthase in the synthesis of dTMP from dUMP?

    <p>It facilitates the transfer of a methyl group from tetrahydrofolate.</p> Signup and view all the answers

    What class of compounds does 5-fluorouracil belong to?

    <p>Thymine analogs</p> Signup and view all the answers

    How does methotrexate affect nucleotide metabolism?

    <p>It reduces the supply of THF necessary for purine synthesis.</p> Signup and view all the answers

    What is produced from the degradation of pyrimidine nucleotides?

    <p>β-alanine and β-aminoisobutyrate</p> Signup and view all the answers

    Which enzyme is inhibited by Trimethoprim, leading to its antibacterial effects?

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

    What is the main source of the methyl group for the conversion of dUMP to dTMP?

    <p>N5,N10-methylene tetrahydrofolate</p> Signup and view all the answers

    What causes 5-FdUMP to permanently inactivate thymidylate synthase?

    <p>It forms a covalent bond with the enzyme.</p> Signup and view all the answers

    Which enzyme utilizes ATP to convert nucleosides into nucleotides?

    <p>Nucleotide kinases</p> Signup and view all the answers

    Study Notes

    Purine Nucleotide Degradation

    • Elevated plasma uric acid levels result from increased PRPP due to X-linked PRPP synthetase mutation.
    • Gout and ADA deficiency are diseases associated with purine metabolism.
    • Lesch-Nyhan syndrome leads to hyperuricemia, resulting from decreased salvage of hypoxanthine/guanine and increased PRPP.
    • Secondary hyperuricemia can arise from myeloproliferative disorders, chemotherapy, and high cell turnover.
    • Underexcretion of uric acid may stem from renal defects or environmental factors like thiazide diuretics and lead exposure.
    • Overproduction of uric acid causes less common hyperuricemia, often idiopathic.

    Adenosine Deaminase (ADA) Deficiency

    • ADA is predominantly found in lymphocytes and its deficiency leads to adenosine accumulation, inhibiting ribonucleotide reductase due to elevated dATP levels.
    • Inhibit DNA production and cell division results in developmental arrest of lymphocytes.
    • Severe combined immunodeficiency disease is the most severe form, characterized by decreased T, B, and NK cells.
    • Treatment options include bone marrow transplant and enzyme replacement therapy; untreated cases often lead to death by age 2.

    Pyrimidine Synthesis and Degradation

    • Pyrimidine ring synthesis occurs before attachment to ribose-5-phosphate from PRPP.
    • Key sources for pyrimidines include glutamine, aspartic acid, and CO2.
    • Carbamoyl phosphate is synthesized from glutamine and CO2, regulated by carbamoyl phosphate synthetase II (CPS II), which is activated by PRPP and inhibited by UTP.
    • Orotic acid synthesis involves the formation of carbamoylaspartate and subsequent reactions to produce orotic acid.
    • UTP is converted to CTP through amination by CTP synthetase, which uses glutamine as nitrogen source.

    Synthesis of TMP from dUMP

    • dUMP is converted to dTMP by thymidylate synthase, which is inhibited by 5-fluorouracil, a suicide inhibitor.
    • N5,N10-methylene tetrahydrofolate provides the methyl group; THF contributes one-carbon units essential for DNA synthesis.
    • Methotrexate decreases THF supply, impacting purine synthesis and DNA replication.
    • Trimethoprim inhibits bacterial dihydrofolate reductase, selectively affecting bacterial growth.

    Pyrimidine Salvage and Degradation

    • Nucleotide kinases catalyze the phosphorylation of nucleosides to nucleotides, crucial for pyrimidine salvage pathways.
    • Uridine treatment is effective for hereditary orotic aciduria.
    • Pyrimidine degradation products are β-alanine, β-aminoisobutyrate, NH3, and CO2, which are highly soluble and less likely to cause inflammation.

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    Biochemistry Nucleotide Metabolism PDF

    Description

    This quiz focuses on the degradation of purine nucleotides in biochemistry, covering related diseases and the impact of X-linked PRPP synthetase mutation on purine production. It delves into how increased PRPP affects plasma uric acid levels and other metabolic pathways.

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