Lippincott's Biochemistry Chapter 22 - Nucleotide Metabolism
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Lippincott's Biochemistry Chapter 22 - Nucleotide Metabolism

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Questions and Answers

What is primarily affected in patients with purine nucleoside phosphorylase deficiency?

  • Antibody production
  • B cell function
  • T cell function (correct)
  • Cytokine release

    • Which of the following treatments is effective for a disorder characterized by negatively birefringent monosodium urate crystals?

  • Bone marrow transplantation (correct)
  • Nucleotide supplementation
  • Chronic corticosteroid therapy
  • Dialysis

    • What is the regulated step in the synthesis of carbamoyl phosphate in mammalian cells?

  • Synthesis from glutamine and carbon dioxide (correct)
  • Phosphorylation of ribose 5-phosphate
  • Hydrolysis of uridine triphosphate
  • Conversion of aspartate to carbamoyl phosphate

    • Which of the following substances inhibits the action of carbamoyl phosphate synthetase II?

    <p>Uridine triphosphate (UTP)</p> Signup and view all the answers

    In the context of nucleotide metabolism disorders, what consequence does a defect in ornithine transcarbamylase lead to?

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

    Children with purine nucleoside phosphorylase deficiency typically die from what complication by age 2 years?

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

    Which factors are sources of the atoms in the pyrimidine ring?

    <p>Glutamine, CO2, and aspartate</p> Signup and view all the answers

    What role does PRPP play in pyrimidine synthesis?

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

    What effect does lactic acidosis have on urate handling by the kidney?

    <p>Increases urate reabsorption</p> Signup and view all the answers

    Which genetic mutation is associated with primary hyperuricemia?

    <p>Mutations in the gene for X-linked PRPP synthetase</p> Signup and view all the answers

    What is the primary treatment option for ADA deficiency?

    <p>Gene therapy</p> Signup and view all the answers

    Which factor is NOT commonly associated with the development of gout?

    <p>Low physical activity</p> Signup and view all the answers

    How does PNP deficiency primarily affect the immune system?

    <p>Disrupts T cell development</p> Signup and view all the answers

    What is the result of high levels of PRPP in purine metabolism?

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

    What is a common consequence of untreated ADA deficiency in children?

    <p>Overwhelming infections</p> Signup and view all the answers

    Which of the following is a characteristic of primary hyperuricemia?

    <p>Idiopathic in nature for most cases</p> Signup and view all the answers

    What enzyme is primarily affected in individuals with PNP deficiency?

    <p>Phosphoribosyl pyrophosphate synthetase</p> Signup and view all the answers

    Which of these treatments is NOT considered for managing hyperuricemia?

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

    What primary issue contributes to hyperuricemia in gout?

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

    Which compounds accumulate as a result of allopurinol treatment?

    <p>Hypoxanthine and xanthine</p> Signup and view all the answers

    The deposition of crystals in gout is primarily due to which substance?

    <p>Monosodium urate</p> Signup and view all the answers

    What is a common genetic factor that can lead to overproduction of uric acid?

    <p>Inborn errors of metabolism</p> Signup and view all the answers

    What role does hypoxanthine play in purine metabolism?

    <p>It is an intermediate in the synthesis of uric acid</p> Signup and view all the answers

    Which treatment strategy is primarily aimed at reducing uric acid levels?

    <p>Use of allopurinol</p> Signup and view all the answers

    Which of the following is NOT a consequence of chronic gout?

    <p>Increased flexibility of joints</p> Signup and view all the answers

    What is the primary mechanism of action of allopurinol in treating gout?

    <p>Inhibits urate synthesis</p> Signup and view all the answers

    What is the primary enzyme responsible for converting ribonucleotides to deoxyribonucleotides?

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

    What condition is caused by a near-total deficiency of HGPRT?

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

    Which condition is characterized by the accumulation of uric acid crystals in the joints?

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

    Which compound is the end product of purine degradation?

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

    What is a key difference between uric acid and its more soluble derivatives produced by allopurinol treatment?

    <p>Uric acid forms crystals, whereas hypoxanthine does not</p> Signup and view all the answers

    Which of the following compounds inhibits the enzyme ribonucleotide reductase?

    <p>Deoxyadenosine triphosphate</p> Signup and view all the answers

    What is triggered when there is overproduction of uric acid accompanied by the deposition of monosodium urate crystals?

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

    Which condition is primarily characterized by elevated levels of uric acid in the blood and potential crystal formation in joints?

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

    Which enzyme deficiency is most commonly linked to hereditary gout?

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

    What is the primary strategy for managing hyperuricemia in patients with a history of gout?

    <p>Use of allopurinol to inhibit uric acid production</p> Signup and view all the answers

    In purine metabolism, which product is generated from the dephosphorylation of ATP?

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

    Which of the following best describes the role of nucleotides in signal transduction pathways?

    <p>They serve as second messengers.</p> Signup and view all the answers

    What is the primary metabolic pathway through which excess purines are redirected for reutilization?

    <p>Salvage pathway</p> Signup and view all the answers

    What genetic disorder is characterized by a deficiency in the enzyme that converts hypoxanthine to xanthine in purine metabolism?

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

    Which nucleotide serves as a precursor in the synthesis of ATP, playing a crucial role in energy metabolism?

    <p>Adenosine triphosphate (ATP)</p> Signup and view all the answers

    Which of the following coenzymes is NOT derived from nucleotides?

    <p>Vitamin B12</p> Signup and view all the answers

    Which statement about the role of ribonucleoside and deoxyribonucleoside phosphates in cells is true?

    <p>They serve as carriers of activated intermediates for metabolism.</p> Signup and view all the answers

    What is the primary consequence of adenosine deaminase (ADA) deficiency in lymphocytes?

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

    Which compound is produced as a long-lived inhibitor of xanthine oxidase from allopurinol?

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

    What role does hypoxanthine play in purine metabolism when ADA is normal?

    <p>It can be salvaged to reduce de novo purine synthesis</p> Signup and view all the answers

    In the context of uric acid metabolism, what is a consequence of treating patients with xanthine oxidase inhibitors like febuxostat?

    <p>Accumulative xanthine leading to potential kidney damage</p> Signup and view all the answers

    Which of the following reflects the antioxidant effect of uric acid in the body?

    <p>It may help prevent oxidative stress-related damage</p> Signup and view all the answers

    What is a primary function of nucleotides in intermediary metabolism?

    <p>They participate as activators or inhibitors of key metabolic enzymes.</p> Signup and view all the answers

    Which nucleotide acts as a second messenger in signal transduction pathways?

    <p>Cyclic guanosine monophosphate (cGMP)</p> Signup and view all the answers

    Which structural component is NOT a part of nucleotide composition?

    <p>Alcohol molecule</p> Signup and view all the answers

    What primary role does the salvage pathway serve in nucleotide metabolism?

    <p>It allows the recycling of preformed bases from cell turnover.</p> Signup and view all the answers

    Which coenzyme is derived from nucleotides and plays a crucial role in metabolic reactions?

    <p>Flavin adenine dinucleotide (FAD)</p> Signup and view all the answers

    What type of nitrogenous bases are adenine and guanine classified as?

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

    Which of the following statements is true regarding dietary intake of purines and pyrimidines?

    <p>Very few dietary purines and pyrimidines are utilized; most are degraded.</p> Signup and view all the answers

    Which step in purine synthesis is primarily associated with the use of 5-phosphoribosyl-1-pyrophosphate (PRPP)?

    <p>Formation of inosine monophosphate (IMP)</p> Signup and view all the answers

    What is the primary purpose of using synthetic inhibitors like sulfonamides in purine synthesis?

    <p>To inhibit rapidly dividing microorganisms</p> Signup and view all the answers

    In purine synthesis, what is the role of N10-formyl-THF?

    <p>Serves as a one-carbon donor</p> Signup and view all the answers

    What is the significance of hypoxanthine in purine metabolism?

    <p>It is involved in the synthesis of tRNA</p> Signup and view all the answers

    What happens when there is an overproduction of PRPP in purine metabolism?

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

    Which of the following accurately describes the role of ATP in the purine synthesis pathway?

    <p>It serves as an energy source in several steps</p> Signup and view all the answers

    Which compound is not typically associated with purine ring synthesis?

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

    What is the most likely outcome of using structural analogs as inhibitors in the purine synthesis pathway?

    <p>Disruption of nucleotide synthesis in pathogens</p> Signup and view all the answers

    Which of the following components is crucial for the initial steps of the purine synthesis pathway?

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

    Which factor plays a role in determining the order of atom addition in the purine ring?

    <p>Enzymatic regulation during synthesis</p> Signup and view all the answers

    What is the role of glutamine in the synthesis of 5-phosphoribosylamine?

    <p>It replaces the pyrophosphate group of PRPP.</p> Signup and view all the answers

    Which substance inhibits glutamine:phosphoribosylpyrophosphate amidotransferase (GPAT)?

    <p>Adenosine monophosphate (AMP)</p> Signup and view all the answers

    What is the relationship between PRPP concentration and the Michaelis constant (Km) for GPAT?

    <p>PRPP concentration is typically below Km.</p> Signup and view all the answers

    Which nucleotide acts as the parent purine nucleotide for AMP and GMP?

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

    During purine nucleotide biosynthesis, which base is associated with inosine monophosphate (IMP)?

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

    What is the significance of the committed step in purine nucleotide biosynthesis?

    <p>It marks the transition from PRPP to purine nucleotides.</p> Signup and view all the answers

    Which condition reflects the regulation of purine metabolism by end products?

    <p>High AMP concentrations inhibit GPAT activity.</p> Signup and view all the answers

    How is inosine monophosphate (IMP) primarily synthesized in purine metabolism?

    <p>Through a series of steps following 5-phosphoribosylamine.</p> Signup and view all the answers

    What effect does increased PRPP concentration have on the rate of purine synthesis?

    <p>It accelerates the synthesis rate.</p> Signup and view all the answers

    What is required as a coenzyme for forming tetrahydrofolate in the purine synthesis pathway?

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

    Which substance is primarily inhibited by methotrexate in purine metabolism?

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

    What is the role of sulfa drugs in bacterial purine synthesis?

    <p>Blocking the pathway to purine synthesis</p> Signup and view all the answers

    Humans rely on external sources for which vitamin essential for purine synthesis?

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

    Which intermediate is produced from the condensation of ribose 5-phosphate in the purine synthesis pathway?

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

    What effect do folic acid analogs have on purine metabolism?

    <p>Inhibit the reduction of dihydrofolate</p> Signup and view all the answers

    What is a primary effect of inhibiting dihydrofolate reductase in bacteria?

    <p>Reduced ability to produce nucleotides</p> Signup and view all the answers

    In purine metabolism, the conversion of what compound is essential for generating ATP?

    <p>Adenosine triphosphate</p> Signup and view all the answers

    Which of the following best describes the function of ribose 5-phosphate in purine synthesis?

    <p>A precursor of nucleotides</p> Signup and view all the answers

    What is the consequence of humans' inability to synthesize folic acid?

    <p>Dependence on dietary sources for nucleotides</p> Signup and view all the answers

    Match the following nucleotide components with their descriptions:

    <p>Nitrogenous base = Can be purines or pyrimidines Pentose monosaccharide = Five-carbon sugar component Phosphate groups = Energy currency in cells Coenzymes = Molecules essential for enzyme function</p> Signup and view all the answers

    Match the following molecules with their primary function:

    <p>cAMP = Second messenger in signal transduction FAD = Electron carrier in metabolism NAD+ = Coenzyme in redox reactions UDP-glucose = Carbohydrate synthesis intermediate</p> Signup and view all the answers

    Match the following nucleotides with their classification:

    <p>Adenine = Purine Cytosine = Pyrimidine Guanine = Purine Thymine = Pyrimidine</p> Signup and view all the answers

    Match the following metabolic roles with their corresponding nucleotides:

    <p>cGMP = Regulatory roles in signaling pathways ATP = Primary energy currency NADP+ = Electron acceptor in biosynthesis cAMP = Regulator of metabolic pathways</p> Signup and view all the answers

    Match the following nucleotide forms with their attributes:

    <p>Ribonucleosides = Contains ribose sugar Deoxyribonucleosides = Contains deoxyribose sugar Monophosphate = Single phosphate group Triphosphate = Three phosphate groups, high energy</p> Signup and view all the answers

    Match the following types of nucleotides with their characteristics:

    <p>Nucleoside monophosphate = Contains one phosphate group Nucleoside diphosphate = Contains two phosphate groups Nucleoside triphosphate = Contains three phosphate groups 5'-ribonucleotide = Derived from ribose sugar</p> Signup and view all the answers

    Match the following terms with their definitions:

    <p>Adenosine monophosphate = A nucleoside monophosphate also known as AMP Adenosine diphosphate = A nucleoside diphosphate also known as ADP Adenosine triphosphate = A nucleoside triphosphate also known as ATP Nucleotide = A nucleoside with one or more phosphate groups</p> Signup and view all the answers

    Match the following types of sugars with their corresponding nucleotide types:

    <p>Deoxyribose = 5'-deoxyribonucleotide Ribose = 5'-ribonucleotide Pentose = Sugar component of nucleotides Nucleotide = Building block of nucleic acids</p> Signup and view all the answers

    Match the following nucleotides with their associated energy characteristics:

    <p>ATP = High-energy molecule ADP = Medium-energy molecule AMP = Low-energy molecule Nucleotide triphosphate = Contributes to energy transfer</p> Signup and view all the answers

    Match the following components to their roles in nucleotide structure:

    <p>Base = Carries genetic information Sugar = Connects to phosphate groups Phosphate = Provides energy storage Nucleoside = Composed of a base and sugar</p> Signup and view all the answers

    Study Notes

    Nucleotide Metabolism Overview

    • Nucleotides are essential for all cells.
    • RNA, DNA, and proteins cannot be produced without nucleotides.
    • Nucleotides act as carriers of intermediates in carbohydrate, lipid, and protein synthesis.
    • They're structural components of coenzymes like FAD, NAD, and NADP.
    • Nucleotides like cAMP and cGMP are second messengers.
    • Nucleotides are crucial energy sources.
    • They regulate numerous metabolic pathways.
    • Purines and pyrimidines can be synthesized de novo or from salvaged precursors.

    Nucleotide Structure

    • Nucleotides consist of a nitrogenous base, a pentose sugar, and one to three phosphate groups.
    • Nitrogenous bases are categorized into purines and pyrimidines.
    • Purines include adenine (A) and guanine (G) and are found in both DNA and RNA.
    • Pyrimidines include cytosine (C), which is present in both DNA and RNA, thymine (T) in DNA, and uracil (U) in RNA.
    • Unusual, modified bases are also present in some DNA and RNA species. Modifications include methylation, glycosylation, acetylation, and reduction.

    Purine Nucleotide Synthesis

    • Purine rings are constructed from amino acids, CO2, and N10-formyltetrahydrofolate.
    • The process primarily occurs in the liver.
    • Ribose 5-phosphate is utilized as a precursor.
    • 5-Phosphoribosyl-1-pyrophosphate (PRPP) plays a key role in the process.
    • Glutamine:phosphoribosylpyrophosphate amidotransferase (GPAT) is a critical enzyme and is regulated by AMP, GMP, and PRPP.
    • Inosine monophosphate (IMP) is a crucial intermediate.
    • AMP and GMP are synthesized from IMP.

    Purine Nucleotide Degradation

    • Pancreatic nucleases hydrolyze dietary nucleic acids in the small intestine.
    • Nucleotides are sequentially degraded into nucleosides, their components, and eventually uric acid.
    • Uric acid is a major end product and is primarily excreted in the urine.
    • Some purines can be salvaged to nucleotides: the enzymes adenine phosphoribosyltransferase (APRT) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT) are involved.
    • Lesch-Nyhan syndrome is an X-linked disorder caused by defects in HGPRT. This results in elevated uric acid, leading to various symptoms.

    Deoxyribonucleotide Synthesis

    • Deoxyribonucleotides are required for DNA synthesis.
    • Ribonucleotide reductase is the key enzyme that converts ribonucleotide diphosphates to deoxyribonucleotide diphosphates.
    • The enzyme itself is crucial for continued synthesis.
    • The enzyme activity is regulated by allosteric sites that bind to products or substrates.
    • Deoxyribonucleotides are essential metabolites for DNA synthesis.

    Pyrimidine Synthesis

    • Pyrimidine ring synthesis occurs before attachment to ribose-5-phosphate.
    • Pyrimidine precursors combine to form the pyrimidine ring.
    • Carbamoyl phosphate synthetase II is a crucial regulatory enzyme in pyrimidine synthesis.
    • Orotate phosphoribosyltransferase catalyzes the conversion of orotate to orotate monophosphate (OMP).
    • OMP decarboxylase converts OMP to uridine monophosphate (UMP).

    Pyrimidine Degradation

    • Degradation produces soluble products like B-aminoisobutyrate and f-alanine.
    • Pyrimidine bases are sometimes salvaged.
    • Pyrimidine bases aren't degraded to the same insoluble product as purines.

    Important Diseases/Conditions

    • Lesch-Nyhan syndrome
    • Gout
    • Orotic aciduria
    • Adenosine deaminase deficiency

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    This quiz explores the vital roles of nucleotides in cellular functions, including their importance in RNA, DNA, and protein synthesis. Learn about the structure of nucleotides, their categories as purines and pyrimidines, and their involvement as energy sources and metabolic regulators.

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