Biochemistry Nucleic Acid Metabolism
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What primarily regulates purine nucleotide synthesis in cells?

  • Activity of ribonucleotide reductase
  • Synthesis of thioredoxin
  • Concentration of PRPP (correct)
  • NADPH availability

    • Which enzyme is responsible for the reduction of ribonucleotides to deoxyribonucleotides?

  • PRPP synthetase
  • Nucleosidase
  • Ribonucleotide reductase (correct)
  • Adenylosuccinate synthetase

    • Which of the following statements about feedback inhibition of purine synthesis is true?

  • AMP and GMP inhibit their respective synthesis from IMP. (correct)
  • PRPP glutamyl amidotransferase is activated by high levels of purine nucleotides.
  • GMP inhibits PRPP synthetase.
  • AMP stimulates the activity of adenylosuccinate synthetase.

    • What is the normal serum concentration of uric acid in adults?

    <p>3-7 mg/dl</p> Signup and view all the answers

    Which of the following conditions is commonly associated with elevated levels of uric acid?

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

    What is the end product of purine metabolism in humans?

    <p>Uric acid</p> Signup and view all the answers

    What substance provides the hydrogen atoms necessary for the reduction during the synthesis of deoxyribonucleotides?

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

    Which mechanism regulates the activity of PRPP glutamyl amidotransferase?

    <p>Feedback inhibition by purine nucleotides</p> Signup and view all the answers

    What role do dietary purines and pyrimidines play in tissue nucleic acids?

    <p>They are not incorporated into tissue nucleic acids.</p> Signup and view all the answers

    Which compounds can be incorporated into DNA following injection?

    <p>Purine and pyrimidine analogues</p> Signup and view all the answers

    What happens to purine bases after their degradation in the body?

    <p>They are oxidized to uric acid.</p> Signup and view all the answers

    What is the primary function of feedback mechanisms in purine and pyrimidine biosynthesis?

    <p>To coordinate their production to match physiological demand.</p> Signup and view all the answers

    What is the structural composition of nucleotides?

    <p>A five-carbon sugar, a nitrogen base, and a phosphate group.</p> Signup and view all the answers

    Why are purines and pyrimidines considered dietarily nonessential?

    <p>Humans can synthesize them from metabolic intermediates.</p> Signup and view all the answers

    What is the result of incorporating injected [3H]thymidine into DNA?

    <p>It measures the rate of DNA synthesis.</p> Signup and view all the answers

    Which of the following statements is true regarding the metabolism of nucleotides?

    <p>Injected purines are metabolized differently than dietary ones.</p> Signup and view all the answers

    What is the primary difference between DNA and RNA in terms of their pyrimidine bases?

    <p>DNA contains thymine, while RNA contains uracil.</p> Signup and view all the answers

    Which nucleotide is first synthesized in the purine nucleotide biosynthesis pathway?

    <p>IMP (inosine mono phosphate)</p> Signup and view all the answers

    Which substance acts as the starting material for purine nucleotide synthesis?

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

    What enzyme is responsible for transferring amide nitrogen in the synthesis of 5-phosphoribosylamine from PRPP?

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

    Which compound donates a formyl group in the biosynthesis of purine nucleotides?

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

    What is formed after aspartate condenses with aminoimidazole carboxylate ribosyl 5-phosphate?

    <p>Aminoimidazole 4-succinyl carboxamide ribosyl 5-phosphate</p> Signup and view all the answers

    How is 5-aminoimidazole ribosyl 5-phosphate formed in purine nucleotide biosynthesis?

    <p>By closing the imidazole ring with the help of ATP.</p> Signup and view all the answers

    Which of these reactions does NOT require biotin or ATP in the carboxylation process?

    <p>Carboxylation of aminoimidazole ribosyl 5-phosphate.</p> Signup and view all the answers

    What role does N10 formyl tetrahydrofolate play in purine synthesis?

    <p>It donates a one-carbon moiety.</p> Signup and view all the answers

    Which compound is formed when IMP undergoes dehydrogenation?

    <p>Xanthosine monophosphate (XMP)</p> Signup and view all the answers

    Which enzyme catalyzes the formation of AMP from adenine in the salvage pathway?

    <p>Adenine phosphoribosyl transferase</p> Signup and view all the answers

    What is the effect of sulfonamides on purine synthesis?

    <p>They inhibit the synthesis of folic acid in microorganisms.</p> Signup and view all the answers

    Which statement about the salvage pathway is true?

    <p>It recovers purines from the turnover of nucleic acids.</p> Signup and view all the answers

    Which enzyme forms GMP from XMP in the purine synthesis process?

    <p>Glutamine-dependent amide transferase</p> Signup and view all the answers

    What is the role of phosphoribosyl pyrophosphate (PRPP) in the salvage pathway?

    <p>It acts as a donor of ribose 5 phosphate.</p> Signup and view all the answers

    Which compound is NOT formed from the cleavage of adenylosuccinate?

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

    What characterizes hyperuricemia?

    <p>Elevated uric acid concentration in serum.</p> Signup and view all the answers

    What process primarily converts ribonucleotides to deoxyribonucleotides?

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

    Which enzyme is crucial for the regulation of IMP conversion to AMP?

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

    Which component is necessary for thioredoxin to provide reducing equivalents?

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

    What is the immediate precursor for the formation of AMP?

    <p>Inosine monophosphate (IMP)</p> Signup and view all the answers

    Which enzyme is responsible for the conversion of guanine to GMP in the salvage pathway?

    <p>Hypoxanthine-guanine phosphoribosyl transferase (HGPRT)</p> Signup and view all the answers

    What is the daily urinary excretion range of uric acid in humans?

    <p>500-700 mg</p> Signup and view all the answers

    What occurs when AMP is available in sufficient amounts concerning purine synthesis?

    <p>Synthesis of AMP is inhibited.</p> Signup and view all the answers

    What role does aspartate play in the synthesis of AMP from IMP?

    <p>It acts as a precursor for adenylosuccinate.</p> Signup and view all the answers

    What is a known consequence of gout?

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

    What is the result of N10 formyl tetrahydrofolate donation in purine synthesis?

    <p>Formation of formimidoimidazole 4-carboxamide ribosyl 5-phosphate.</p> Signup and view all the answers

    What is the effect of sulfonamides on microbial folic acid synthesis?

    <p>They inhibit the synthesis of folic acid.</p> Signup and view all the answers

    Which reaction is inhibited by GMP during purine synthesis regulation?

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

    Which of the following compounds does NOT play a role in the synthesis of purine nucleotides?

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

    What is the significance of the salvage pathway for purines?

    <p>It provides a mechanism to recycle purines from nucleotide turnover.</p> Signup and view all the answers

    Which compound is produced from the closure of the ring in formimidoimidazole ribosyl-5-P by enzyme cyclohydrolase?

    <p>Inosine monophosphate (IMP)</p> Signup and view all the answers

    What is the first purine nucleotide synthesized in the biosynthesis pathway?

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

    Which of the following statements is true regarding the role of ribose 5-phosphate in purine nucleotide synthesis?

    <p>It forms phosphoribosyl pyrophosphate (PRPP) after reacting with ATP.</p> Signup and view all the answers

    Which nitrogen atom source contributes to the synthesis of the purine ring?

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

    Which enzyme is primarily responsible for the transfer of amide nitrogen to PRPP to produce 5-phosphoribosylamine?

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

    What is the role of N5,N10 formyl tetrahydrofolate in purine nucleotide biosynthesis?

    <p>It donates the formyl group to form a purine derivative.</p> Signup and view all the answers

    What product is formed after the imidazole ring of the purine is closed in the synthesis process?

    <p>5-Aminoimidazole ribosyl 5-phosphate</p> Signup and view all the answers

    Which compound is synthesized from glycine during the early steps of purine nucleotide biosynthesis?

    <p>Glycinamide ribotide</p> Signup and view all the answers

    In the purine biosynthesis pathway, which reaction does NOT require biotin or ATP?

    <p>Formation of aminoimidazole carboxylate ribosyl 5-phosphate</p> Signup and view all the answers

    What is a key characteristic of dietary nucleic acids in humans?

    <p>They are not essential for nucleic acid synthesis.</p> Signup and view all the answers

    Which process describes how purine bases are handled after degradation?

    <p>They are oxidized to uric acid.</p> Signup and view all the answers

    What can be used to measure the rate of DNA synthesis in cells?

    <p>Injected [3H]thymidine.</p> Signup and view all the answers

    What is the composition of nucleotides?

    <p>A sugar, a nitrogen base, and a phosphate group.</p> Signup and view all the answers

    Why are purines and pyrimidines categorized as dietarily nonessential?

    <p>They are synthesized from amphibolic intermediates.</p> Signup and view all the answers

    What role do feedback mechanisms play in nucleotide biosynthesis?

    <p>They ensure production aligns with physiological demand.</p> Signup and view all the answers

    Which component of nucleotides is absent in nucleosides?

    <p>Phosphate group.</p> Signup and view all the answers

    Following degradation, how may mononucleotides impact purine and pyrimidine metabolism?

    <p>They can be converted to purine and pyrimidine bases.</p> Signup and view all the answers

    Study Notes

    Module: Biochemistry Nucleic Acid Metabolism

    • The module focuses on the metabolism of nucleic acids, specifically purines and pyrimidines.
    • Learning objectives include comparing and contrasting dietary nucleic acids and de novo biosynthesis in purine and pyrimidine production.
    • The sequence of reactions converting IMP to AMP and GMP, and subsequent nucleoside triphosphates, is outlined.
    • Degradation of nucleotides is also discussed.

    Biomedical Importance

    • Humans synthesize nucleic acids (ATP, NAD+, etc.) from amphibolic intermediates.
    • Dietary purines and pyrimidines are not directly incorporated, but injected analogues might be.
    • Biosynthesis of purine and pyrimidine ribonucleotide triphosphates (NTPs) and dNTPs are carefully controlled.
    • Production occurs at appropriate quantities and times matching physiological demands (e.g., cell division).

    Nucleic Acid Structure

    • Nucleotides are fundamental to all cells.
    • They act as carriers of activated intermediates in carbohydrates, lipids, and proteins.
    • Nucleotides consist of a five-carbon sugar (ribose or deoxyribose), a nitrogenous base (purine or pyrimidine), and a phosphate group.
    • Nucleosides lack the phosphate group.
    • DNA and RNA share adenine (A) and guanine (G).
    • Both contain cytosine (C) but differ in their second pyrimidine base. DNA has thymine (T) and RNA has uracil (U).

    Purines and Pyrimidines

    • Purines and pyrimidines in human tissue are synthesized from amphibolic intermediates to meet physiological demand. Ingested nucleic acids are thus not essential.
    • Following intestinal degradation, resulting mononucleotides can be absorbed or converted to purine or pyrimidine bases.
    • Purine bases are oxidized to uric acid, which is excreted in urine.
    • Injected [3H]thymidine incorporation in DNA, measures DNA synthesis rate.

    Purine Nucleotide Biosynthesis

    • Purine nucleotide biosynthesis involves three main processes; synthesis de novo, phosphoribosylation of purines, and phosphorylation of purine nucleosides.
    • Carbon and nitrogen atoms of the purine ring come from glycine, glutamate, and other sources.
    • The initial parent nucleotide synthesized is IMP (inosine monophosphate), a nucleotide composed of hypoxanthine, ribose, and phosphate.
    • Ribose-5-phosphate, a product of the hexose monophosphate shunt, is the starting material for purine nucleotide synthesis. It reacts with ATP to form phosphoribosyl pyrophosphate (PRPP).
    • Specific enzymes (e.g., PRPP synthetase) are involved in this initial step in the biosynthesis.
    • Glutamine amidotransferase transfers nitrogen to PRPP to form 5-phosphoribosylamine. This reaction is controlled by feedback inhibition.
    • Subsequent reactions involve glycine, N5,N10-formyltetrahydrofolate and glutamine, leading to the production of formylglycinamide ribonucleotide.
    • Further enzymatic steps lead to the closure of the imidazole ring and the synthesis of aminoimidazole carboxylate ribonucleotide.
    • Incorporation of CO2 forms aminoimidazole carboxylate ribonucleotide.
    • Aspartate then adds to the chain.
    • Adenosuccinase reaction produces aminoimidazole carboxamide ribonucleotide.
    • Lastly, N10-formyltetrahydrofolate and other enzymatic reactions finalize the formation of inosine monophosphate (IMP).
    • The synthesis of AMP and GMP from IMP involves specific reaction sequences using nucleotides like GTP, including steps involving adenylosuccinate and xanthosine monophosphate/ GMP.

    Regulation of Purine Nucleotide Synthesis

    • Synthesis is regulated to meet cellular demand.
    • Intracellular concentration of PRPP regulates synthesis, depending on ribose 5-phosphate availability and PRPP synthetase activity.
    • Further control (feedback inhibition) happens at the amidotransferase reaction if AMP or GMP are present in sufficient quantity.
    • AMP influences adenylosuccinate synthetase and GMP affects IMP dehydrogenase.

    Nucleoside Di- and Triphosphates

    • Nucleotide monophosphates are converted to di- and triphosphates using ATP and kinases.

    Conversion of Ribonucleotides to Deoxynucleotides

    • Deoxyribonucleotides are formed from ribonucleotides via the enzyme ribonucleotide reductase (which provides reducing equivalents), a reaction requiring thioredoxin and NADPH-dependent thioredoxin reductase.

    Degradation of Purine Nucleotides

    • The end product of purine metabolism is uric acid.
    • Nucleotide monophosphates are converted to nucleosides; amino groups are removed from AMP or adenosine to produce IMP or inosine.
    • These intermediates further degrade to xanthine or uric acid, via the action of specific enzymes such as xanthine oxidase.

    Disorders of Purine Metabolism

    • Hyperuricemia refers to elevated serum uric acid and can be associated with increased excretion (uricosuria).
    • Gout is a metabolic disorder characterized by overproduction of uric acid and can lead to build-up of sodium urate crystals in tissues like joints in severe cases.

    Salvage Pathway for Purines

    • Free purines (adenine, guanine, hypoxanthine) are formed during nucleic acid turnover or from diet.
    • These purines can be converted to nucleotides; this process in known as ''salvage pathway''.
    • Adenine phosphoribosyl transferase forms AMP from adenine.
    • Hypoxanthine-guanine phosphoribosyl transferase forms GMP and IMP from guanine or hypoxanthine respectively, with PRPP as the ribose donor.

    Inhibitors of Purine Synthesis

    • Sulfonamides are structural analogs of para-aminobenzoic acid (PABA).
    • PABA inhibits the synthesis of folic acid by microorganisms, so sulfa drugs indirectly diminish purine and nucleic acid, DNA and RNA, synthesis. This doesn't affect humans since we obtain folic acid from our diet.
    • Structural analogs to folic acid, such as methotrexate, block purine synthesis and nucleic acid production, which can control cancer proliferation but also usually impact normal cell growth as well.

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    Description

    This quiz covers the metabolism of nucleic acids, focusing on the synthesis and degradation of purines and pyrimidines. It explores the biochemical pathways for converting IMP to AMP and GMP, as well as the significance of nucleotides in cellular functions. Learn about dietary nucleic acids and their incorporation into human metabolism.

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