Biochemistry Nucleotide Metabolism Part 2
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Questions and Answers

What is a consequence of lactic acidosis on uric acid excretion?

  • It increases the renal reabsorption of urate.
  • It leads to accumulation of hypoxanthine and xanthine. (correct)
  • It decreases competition for renal transporters.
  • It enhances the solubility of uric acid.
  • Which of the following correctly describes the role of oxypurinol?

  • It is an active form of adenosine deaminase.
  • It acts as a non-purine inhibitor of xanthine oxidase. (correct)
  • It converts xanthine to uric acid.
  • It promotes uric acid excretion from the kidneys.
  • In the context of uric acid metabolism, what is the significance of a normal HGPRT level?

  • It suggests increased risk of lactic acidosis.
  • It indicates high levels of uric acid synthesis.
  • It ensures proper hypoxanthine salvage for de novo synthesis. (correct)
  • It is a marker for uric acid overproduction.
  • Which drug is known as a non-purine inhibitor of xanthine oxidase?

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

    Which of the following is a primary cause of underexcretion of uric acid?

    <p>As-yet-unidentified inherent excretory defects</p> Signup and view all the answers

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

    <p>Increased PRPP leading to elevated purine production</p> Signup and view all the answers

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

    <p>Lesch-Nyhan syndrome</p> Signup and view all the answers

    In cases of secondary hyperuricemia, what is a common underlying cause?

    <p>High rates of cell turnover</p> Signup and view all the answers

    What is the primary consequence of increased levels of PRPP in nucleotide metabolism?

    <p>Increased plasma concentrations of uric acid</p> Signup and view all the answers

    Which of the following is a potential consequence of ADA deficiency?

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

    Which process is involved in the synthesis of UTP and CTP?

    <p>Synthesis of orotic acid</p> Signup and view all the answers

    What is the consequence of decreased salvage activity in purine nucleotides?

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

    Which of the following statements about pyrimidine metabolism is false?

    <p>Synthesis of TMP from dUMP does not involve UTP.</p> Signup and view all the answers

    What characterizes gout in relation to purine catabolism?

    <p>It is identified by needle-shaped crystals in the joints.</p> Signup and view all the answers

    Which of the following is a nonsteroidal anti-inflammatory drug used to treat gout?

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

    What condition arises from the deposition of monosodium urate crystals?

    <p>Chronic tophaceous gout</p> Signup and view all the answers

    How does colchicine function in treating gout?

    <p>It prevents microtubule formation.</p> Signup and view all the answers

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

    <p>Polarized light microscopy of synovial fluid</p> Signup and view all the answers

    Which dietary habit is associated with an increased risk of developing gout?

    <p>Consuming a diet rich in meat and seafood</p> Signup and view all the answers

    What is the primary purpose of uricosuric agents in gout treatment?

    <p>To lower uric acid below its saturation point</p> Signup and view all the answers

    Which of the following is NOT a characteristic of hyperuricemia?

    <p>Always symptomatic</p> Signup and view all the answers

    What treatment option is often used for underexcretors of uric acid?

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

    Which of the following conditions is characterized by the increased production of uric acid?

    <p>Von Gierke disease</p> Signup and view all the answers

    Which compound acts as a suicide inhibitor of thymidylate synthase?

    <p>5-fluorouracil</p> Signup and view all the answers

    What is the primary source of the methyl group in the synthesis of thymidine monophosphate from dUMP?

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

    Which of the following compounds is inhibited by Methotrexate?

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

    In the degradation of pyrimidine nucleotides, which of the following is NOT a product?

    <p>Succinyl-CoA</p> Signup and view all the answers

    What role do nucleotide kinases play in nucleotide metabolism?

    <p>Phosphorylate nucleosides to form nucleotides</p> Signup and view all the answers

    What is a major effect of inhibiting thymidylate synthase?

    <p>Inhibition of DNA synthesis and cell growth</p> Signup and view all the answers

    Which molecule is primarily linked to the antibacterial activity of Trimethoprim?

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

    Which condition is treated with uridine due to its role in nucleotide metabolism?

    <p>Orotic aciduria</p> Signup and view all the answers

    What is the role of UTP in the regulation of carbamoyl phosphate synthesis?

    <p>It inhibits carbamoyl phosphate synthetase II.</p> Signup and view all the answers

    Which enzyme is responsible for the transformation of aspartate into carbamoylaspartate?

    <p>Aspartate transcarbamoylase</p> Signup and view all the answers

    What is the function of dihydroorotase in pyrimidine synthesis?

    <p>It hydrolytically closes carbamoylaspartate.</p> Signup and view all the answers

    How does PRPP affect carbamoyl phosphate synthetase II activity?

    <p>It enhances the activity of CPS II.</p> Signup and view all the answers

    What is the direct precursor of urea in the metabolic pathway discussed?

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

    What is the primary role of glutamine in carbamoyl phosphate synthesis?

    <p>It donates nitrogen for the synthesis.</p> Signup and view all the answers

    Which of the following enzymes is not involved in the synthesis of UTP and CTP?

    <p>Ornithine transcarbamylase</p> Signup and view all the answers

    Which metabolic step is associated with the formation of orotic acid?

    <p>Oxidation of dihydroorotate</p> Signup and view all the answers

    Study Notes

    Purine Nucleotide Degradation

    • X-linked PRPP synthetase mutation increases PRPP levels, enhancing purine production and elevating plasma uric acid.
    • Associated diseases include gout and adenosine deaminase (ADA) deficiency.
    • Gout results from hyperuricemia, linked to purine overproduction or underexcretion, leading to monosodium urate crystal deposition in joints, soft tissues, and kidneys.
    • Dietary factors influence gout risk: high meat/seafood increases risk; low-fat dairy decreases risk.
    • Gout treatment includes anti-inflammatory agents (colchicine, prednisone, indomethacin) and uricosuric agents (probenecid, sulfinpyrazone) to lower uric acid levels.
    • Allopurinol inhibits uric acid synthesis and promotes hypoxanthine accumulation, which is more soluble and less inflammatory.

    Purine Synthesis and Associated Disorders

    • Underexcretion of uric acid can be primary (unknown defects) or secondary to other diseases affecting renal handling of urate, like lactic acidosis or drug effects (thiazide diuretics, lead exposure).
    • Increased PRPP levels can exacerbate conditions like Lesch-Nyhan syndrome, characterized by hyperuricemia due to decreased salvage of hypoxanthine and guanine.

    Pyrimidine Synthesis and Degradation

    • Carbamoyl phosphate is synthesized from glutamine and CO2; this step is regulated by CPS II, with UTP inhibiting and PRPP activating the process.
    • Synthesis of orotic acid involves the formation of carbamoylaspartate and oxidation to orotic acid through specific enzymes (aspartate transcarbamoylase, dihydroorotase, dihydroorotate dehydrogenase).
    • UTP is converted to CTP via amination; ribonucleotide reductase then helps synthesize dCTP for DNA.

    Thymidine Synthesis and Regulation

    • TMP is synthesized from dUMP, with thymidylate synthase playing a crucial role; it is inhibited by 5-fluorouracil, leading to decreased DNA synthesis.
    • Methotrexate inhibits dihydrofolate reductase, reducing THF supply and consequently inhibiting purine and TMP synthesis, slowing cell growth.

    Pyrimidine Salvage and Degradation

    • Salvage pathways involve nucleotide kinases utilizing ATP for nucleoside phosphorylation; uridine is beneficial in hereditary orotic aciduria treatment.
    • Pyrimidine nucleotides degrade into soluble products, including β-alanine, β-aminoisobutyrate, ammonia, and carbon dioxide.

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    Description

    This quiz covers the degradation of purine nucleotides, including the effects of X-linked PRPP synthetase mutation and its association with elevated plasma uric acid levels. Understand the metabolic pathways and related diseases. Test your knowledge on the complexities of nucleotide metabolism in biochemistry.

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