Podcast
Questions and Answers
Which molecule is consumed to ensure irreversibility in the intramolecular reaction in which the nucleophile and phosphate-activated carbon atom AIR synthetase (FGAM cyclase)?
Which molecule is consumed to ensure irreversibility in the intramolecular reaction in which the nucleophile and phosphate-activated carbon atom AIR synthetase (FGAM cyclase)?
What is the potent inhibitor of CTP and GMP synthetases that partially inhibits FGAM synthetase?
What is the potent inhibitor of CTP and GMP synthetases that partially inhibits FGAM synthetase?
Which enzyme catalyzes the removal of fumarate from 5-aminoimidazole-4-N-succinocarboxamide ribonucleotide in the synthesis of inosinate?
Which enzyme catalyzes the removal of fumarate from 5-aminoimidazole-4-N-succinocarboxamide ribonucleotide in the synthesis of inosinate?
What is the hydrogen acceptor in the oxidation of inosinate to xanthylate?
What is the hydrogen acceptor in the oxidation of inosinate to xanthylate?
Signup and view all the answers
What is the reciprocal use of nucleotides by the pathways an important regulatory opportunity for?
What is the reciprocal use of nucleotides by the pathways an important regulatory opportunity for?
Signup and view all the answers
What is the final intermediate formed by the addition of a formyl group from N10-formyltetrahydrofolate to a nitrogen atom?
What is the final intermediate formed by the addition of a formyl group from N10-formyltetrahydrofolate to a nitrogen atom?
Signup and view all the answers
What is the potent, reversible, uncompetitive inhibitor of inosine monophosphate dehydrogenase used successfully in preventing graft rejection?
What is the potent, reversible, uncompetitive inhibitor of inosine monophosphate dehydrogenase used successfully in preventing graft rejection?
Signup and view all the answers
What does mycophenolic acid block in the de novo pathway of purine synthesis?
What does mycophenolic acid block in the de novo pathway of purine synthesis?
Signup and view all the answers
What is the final carbon contributed by in the synthesis of the second fused ring of the purine nucleus?
What is the final carbon contributed by in the synthesis of the second fused ring of the purine nucleus?
Signup and view all the answers
What is the molecule required for the substitution of NH3 for the c=0 oxygen atom at C-6 in the synthesis of adenylate from inosinate?
What is the molecule required for the substitution of NH3 for the c=0 oxygen atom at C-6 in the synthesis of adenylate from inosinate?
Signup and view all the answers
Which nucleotide is required for capping of mRNA?
Which nucleotide is required for capping of mRNA?
Signup and view all the answers
What is the precursor for the formation of tetrahydrobiopterin, required for hydroxylation reactions and nitric oxide generation?
What is the precursor for the formation of tetrahydrobiopterin, required for hydroxylation reactions and nitric oxide generation?
Signup and view all the answers
Which nucleotide is important in the control of coronary blood flow?
Which nucleotide is important in the control of coronary blood flow?
Signup and view all the answers
Which nucleotide is required for the synthesis of sulfated biomolecules such as proteoglycans and sulfatides?
Which nucleotide is required for the synthesis of sulfated biomolecules such as proteoglycans and sulfatides?
Signup and view all the answers
In which type of cells do adenine nucleotides far exceed the concentrations of guanine, cytosine, and uridine nucleotides?
In which type of cells do adenine nucleotides far exceed the concentrations of guanine, cytosine, and uridine nucleotides?
Signup and view all the answers
What is the ratio whose alteration depends on the energy state of the cell?
What is the ratio whose alteration depends on the energy state of the cell?
Signup and view all the answers
Which class of pathways leads to the synthesis of deoxyribonucleotides from the corresponding ribonucleotides?
Which class of pathways leads to the synthesis of deoxyribonucleotides from the corresponding ribonucleotides?
Signup and view all the answers
What do coenzymes NAD+, NADP+, FAD, and coenzyme A contain as part of their structures?
What do coenzymes NAD+, NADP+, FAD, and coenzyme A contain as part of their structures?
Signup and view all the answers
What is the activated intermediate that participates in biosynthetic processes such as glycogen synthesis?
What is the activated intermediate that participates in biosynthetic processes such as glycogen synthesis?
Signup and view all the answers
Which nucleotide predominates in hypoxic cells?
Which nucleotide predominates in hypoxic cells?
Signup and view all the answers
Which enzyme catalyzes the conversion of phosphoribosyl pyrophosphate (PRPP) to 5-phosphoribosylamine, the committed step in purine biosynthesis?
Which enzyme catalyzes the conversion of phosphoribosyl pyrophosphate (PRPP) to 5-phosphoribosylamine, the committed step in purine biosynthesis?
Signup and view all the answers
Which enzyme is responsible for the activation of the glycine carboxyl group by consuming ATP in the purine biosynthesis pathway?
Which enzyme is responsible for the activation of the glycine carboxyl group by consuming ATP in the purine biosynthesis pathway?
Signup and view all the answers
Which enzyme catalyzes the formation of N-glycosidic bond of the purine nucleotide in the purine biosynthesis pathway?
Which enzyme catalyzes the formation of N-glycosidic bond of the purine nucleotide in the purine biosynthesis pathway?
Signup and view all the answers
Which enzyme is expressed for longer in individuals with Down Syndrome?
Which enzyme is expressed for longer in individuals with Down Syndrome?
Signup and view all the answers
Which enzyme is responsible for transferring the formyl group from N10-formyltetrahydrofolate to glycine in the purine biosynthesis pathway?
Which enzyme is responsible for transferring the formyl group from N10-formyltetrahydrofolate to glycine in the purine biosynthesis pathway?
Signup and view all the answers
Which enzyme is involved in the synthesis of tetrahydrofolate, a carrier of activated one-carbon units?
Which enzyme is involved in the synthesis of tetrahydrofolate, a carrier of activated one-carbon units?
Signup and view all the answers
Which enzyme catalyzes the conversion of dihydrofolate to tetrahydrofolate in mammals?
Which enzyme catalyzes the conversion of dihydrofolate to tetrahydrofolate in mammals?
Signup and view all the answers
Which compound is an analog of glutamine and a purine antagonist with antineoplastic properties?
Which compound is an analog of glutamine and a purine antagonist with antineoplastic properties?
Signup and view all the answers
Which drug inhibits bacterial dihydrofolate reductase and has potent antibacterial activity?
Which drug inhibits bacterial dihydrofolate reductase and has potent antibacterial activity?
Signup and view all the answers
Which drug is a structural analog of folic acid and is used to control the spread of cancer by interfering with nucleotides for DNA and RNA?
Which drug is a structural analog of folic acid and is used to control the spread of cancer by interfering with nucleotides for DNA and RNA?
Signup and view all the answers
Which of the following is true about nucleotide biosynthesis?
Which of the following is true about nucleotide biosynthesis?
Signup and view all the answers
What is the precursor for the formation of the cofactor tetrahydrobiopterin?
What is the precursor for the formation of the cofactor tetrahydrobiopterin?
Signup and view all the answers
In which type of cells do adenine nucleotides far exceed the concentrations of guanine, cytosine, and uridine nucleotides?
In which type of cells do adenine nucleotides far exceed the concentrations of guanine, cytosine, and uridine nucleotides?
Signup and view all the answers
What is the ratio altered depending on the energy state of the cell?
What is the ratio altered depending on the energy state of the cell?
Signup and view all the answers
Which class do nucleotides fall into, leading to the synthesis of ribonucleotides?
Which class do nucleotides fall into, leading to the synthesis of ribonucleotides?
Signup and view all the answers
What is the activated precursor of nucleic acids necessary for the replication of the genome?
What is the activated precursor of nucleic acids necessary for the replication of the genome?
Signup and view all the answers
Which nucleotide is important in the control of coronary blood flow?
Which nucleotide is important in the control of coronary blood flow?
Signup and view all the answers
What is the methyl donor in the formation of phosphatidylcholine from phosphatidylethanolamine?
What is the methyl donor in the formation of phosphatidylcholine from phosphatidylethanolamine?
Signup and view all the answers
What is the sulfate donor to generate sulfated biomolecules such as proteoglycans and sulfatides?
What is the sulfate donor to generate sulfated biomolecules such as proteoglycans and sulfatides?
Signup and view all the answers
What do coenzymes NAD+, NADP+, FAD and their reduced forms all contain as part of their structures?
What do coenzymes NAD+, NADP+, FAD and their reduced forms all contain as part of their structures?
Signup and view all the answers
Which enzyme catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate (PRPP) to 5-phosphoribosylamine, the committed step in purine biosynthesis?
Which enzyme catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate (PRPP) to 5-phosphoribosylamine, the committed step in purine biosynthesis?
Signup and view all the answers
Which molecule is consumed to ensure irreversibility in the intramolecular reaction in which the nucleophile and phosphate-activated carbon atom AIR synthetase (FGAM cyclase)?
Which molecule is consumed to ensure irreversibility in the intramolecular reaction in which the nucleophile and phosphate-activated carbon atom AIR synthetase (FGAM cyclase)?
Signup and view all the answers
What is the final intermediate formed by the addition of a formyl group from N10-formyltetrahydrofolate to a nitrogen atom?
What is the final intermediate formed by the addition of a formyl group from N10-formyltetrahydrofolate to a nitrogen atom?
Signup and view all the answers
Which enzyme catalyzes the conversion of dihydrofolate to tetrahydrofolate in mammals?
Which enzyme catalyzes the conversion of dihydrofolate to tetrahydrofolate in mammals?
Signup and view all the answers
Which enzyme is responsible for transferring the formyl group from N10-formyltetrahydrofolate to glycine in the purine biosynthesis pathway?
Which enzyme is responsible for transferring the formyl group from N10-formyltetrahydrofolate to glycine in the purine biosynthesis pathway?
Signup and view all the answers
What is the potent inhibitor of CTP and GMP synthetases that partially inhibits FGAM synthetase?
What is the potent inhibitor of CTP and GMP synthetases that partially inhibits FGAM synthetase?
Signup and view all the answers
What is the activated precursor of nucleic acids necessary for the replication of the genome?
What is the activated precursor of nucleic acids necessary for the replication of the genome?
Signup and view all the answers
Which enzyme catalyzes the removal of fumarate from 5-aminoimidazole-4-N-succinocarboxamide ribonucleotide in the synthesis of inosinate?
Which enzyme catalyzes the removal of fumarate from 5-aminoimidazole-4-N-succinocarboxamide ribonucleotide in the synthesis of inosinate?
Signup and view all the answers
Which enzyme catalyzes the formation of N-glycosidic bond of the purine nucleotide in the purine biosynthesis pathway?
Which enzyme catalyzes the formation of N-glycosidic bond of the purine nucleotide in the purine biosynthesis pathway?
Signup and view all the answers
Which molecule is the common precursor for AMP and GMP in purine biosynthesis?
Which molecule is the common precursor for AMP and GMP in purine biosynthesis?
Signup and view all the answers
How many moles of ATP are utilized per mole of IMP synthesized in purine nucleotide synthesis?
How many moles of ATP are utilized per mole of IMP synthesized in purine nucleotide synthesis?
Signup and view all the answers
Where are all enzymes involved in the synthesis of purine nucleotides found?
Where are all enzymes involved in the synthesis of purine nucleotides found?
Signup and view all the answers
Which condition can result from mutations in the X-linked recessive PRPP SYNTHASE/RPDPKINASE?
Which condition can result from mutations in the X-linked recessive PRPP SYNTHASE/RPDPKINASE?
Signup and view all the answers
Which enzyme catalyzes the committed step in purine biosynthesis, forming the N-glycosidic bond of the purine nucleotide?
Which enzyme catalyzes the committed step in purine biosynthesis, forming the N-glycosidic bond of the purine nucleotide?
Signup and view all the answers
What is the carrier of activated one-carbon units obtained from diets or microorganisms in intestinal tracts?
What is the carrier of activated one-carbon units obtained from diets or microorganisms in intestinal tracts?
Signup and view all the answers
Which compound selectively inhibits bacterial dihydrofolate reductase and has potent antibacterial activity?
Which compound selectively inhibits bacterial dihydrofolate reductase and has potent antibacterial activity?
Signup and view all the answers
What is the structural analog of folic acid used to control cancer spread by interfering with nucleotides for DNA and RNA?
What is the structural analog of folic acid used to control cancer spread by interfering with nucleotides for DNA and RNA?
Signup and view all the answers
What can rescue normal cells from the toxic effects of methotrexate by acting as a synthetic inhibitor of purine synthesis?
What can rescue normal cells from the toxic effects of methotrexate by acting as a synthetic inhibitor of purine synthesis?
Signup and view all the answers
What is the name of the purine antagonists with antineoplastic and antibiotic properties, inhibiting amidotransferases?
What is the name of the purine antagonists with antineoplastic and antibiotic properties, inhibiting amidotransferases?
Signup and view all the answers
What is the phosphoryl-grp donor for the synthesis of adenylsuccinate?
What is the phosphoryl-grp donor for the synthesis of adenylsuccinate?
Signup and view all the answers
What is the hydrogen acceptor in the oxidation of inosinate to xanthylate?
What is the hydrogen acceptor in the oxidation of inosinate to xanthylate?
Signup and view all the answers
What is the reciprocal use of nucleotides by the pathways an important regulatory opportunity for?
What is the reciprocal use of nucleotides by the pathways an important regulatory opportunity for?
Signup and view all the answers
What is the potent, reversible, uncompetitive inhibitor of inosine monophosphate dehydrogenase?
What is the potent, reversible, uncompetitive inhibitor of inosine monophosphate dehydrogenase?
Signup and view all the answers
Which nucleotide is required for the synthesis of adenylate?
Which nucleotide is required for the synthesis of adenylate?
Signup and view all the answers
Which nucleotide is required for the synthesis of guanylate?
Which nucleotide is required for the synthesis of guanylate?
Signup and view all the answers
What is the carrier of activated one-carbon units obtained from diets or microorganisms in intestinal tracts?
What is the carrier of activated one-carbon units obtained from diets or microorganisms in intestinal tracts?
Signup and view all the answers
What is the final intermediate formed by the addition of a formyl group from N10-formyltetrahydrofolate to a nitrogen atom?
What is the final intermediate formed by the addition of a formyl group from N10-formyltetrahydrofolate to a nitrogen atom?
Signup and view all the answers
What is the molecule required for the substitution of NH3 for the c=0 oxygen atom at C-6 in the synthesis of adenylate from inosinate?
What is the molecule required for the substitution of NH3 for the c=0 oxygen atom at C-6 in the synthesis of adenylate from inosinate?
Signup and view all the answers
What is the activated intermediate that participates in biosynthetic processes such as glycogen synthesis?
What is the activated intermediate that participates in biosynthetic processes such as glycogen synthesis?
Signup and view all the answers
Which enzyme is involved in the first step synthesis of carbamoyl phosphate from bicarbonate and ammonia?
Which enzyme is involved in the first step synthesis of carbamoyl phosphate from bicarbonate and ammonia?
Signup and view all the answers
Which enzyme is responsible for transferring the formyl group from N10-formyltetrahydrofolate to glycine in the purine biosynthesis pathway?
Which enzyme is responsible for transferring the formyl group from N10-formyltetrahydrofolate to glycine in the purine biosynthesis pathway?
Signup and view all the answers
Which enzyme catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate (PRPP) to 5-phosphoribosylamine, the committed step in purine biosynthesis?
Which enzyme catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate (PRPP) to 5-phosphoribosylamine, the committed step in purine biosynthesis?
Signup and view all the answers
Which enzyme catalyzes the removal of fumarate from 5-aminoimidazole-4-N-succinocarboxamide ribonucleotide in the synthesis of inosinate?
Which enzyme catalyzes the removal of fumarate from 5-aminoimidazole-4-N-succinocarboxamide ribonucleotide in the synthesis of inosinate?
Signup and view all the answers
What is the precursor for the formation of the cofactor tetrahydrobiopterin?
What is the precursor for the formation of the cofactor tetrahydrobiopterin?
Signup and view all the answers
Which enzyme catalyzes the conversion of dihydrofolate to tetrahydrofolate in mammals?
Which enzyme catalyzes the conversion of dihydrofolate to tetrahydrofolate in mammals?
Signup and view all the answers
Which enzyme is responsible for the activation of the glycine carboxyl group by consuming ATP in the purine biosynthesis pathway?
Which enzyme is responsible for the activation of the glycine carboxyl group by consuming ATP in the purine biosynthesis pathway?
Signup and view all the answers
What is the activated precursor of nucleic acids necessary for the replication of the genome?
What is the activated precursor of nucleic acids necessary for the replication of the genome?
Signup and view all the answers
What is the molecule required for the substitution of NH3 for the C=O oxygen atom at C-6 in the synthesis of adenylate from inosinate?
What is the molecule required for the substitution of NH3 for the C=O oxygen atom at C-6 in the synthesis of adenylate from inosinate?
Signup and view all the answers
What do coenzymes NAD+, NADP+, FAD, and coenzyme A contain as part of their structures?
What do coenzymes NAD+, NADP+, FAD, and coenzyme A contain as part of their structures?
Signup and view all the answers
Which enzyme is involved in the synthesis of tetrahydrofolate, a carrier of activated one-carbon units?
Which enzyme is involved in the synthesis of tetrahydrofolate, a carrier of activated one-carbon units?
Signup and view all the answers
Which drug is a structural analog of folic acid and is used to control the spread of cancer by interfering with nucleotides for DNA and RNA?
Which drug is a structural analog of folic acid and is used to control the spread of cancer by interfering with nucleotides for DNA and RNA?
Signup and view all the answers
What is the final carbon contributed by in the synthesis of the second fused ring of the purine nucleus?
What is the final carbon contributed by in the synthesis of the second fused ring of the purine nucleus?
Signup and view all the answers
Which compound is consumed to ensure irreversibility in the intramolecular reaction in which the nucleophile and phosphate-activated carbon atom AIR synthetase (FGAM cyclase)?
Which compound is consumed to ensure irreversibility in the intramolecular reaction in which the nucleophile and phosphate-activated carbon atom AIR synthetase (FGAM cyclase)?
Signup and view all the answers
Which enzyme catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate (PRPP) to 5-phosphoribosylamine, the committed step in purine biosynthesis?
Which enzyme catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate (PRPP) to 5-phosphoribosylamine, the committed step in purine biosynthesis?
Signup and view all the answers
Which enzyme is particularly active in high energy turnover tissues like liver and muscle?
Which enzyme is particularly active in high energy turnover tissues like liver and muscle?
Signup and view all the answers
What is the activated precursor of nucleic acids necessary for the replication of the genome?
What is the activated precursor of nucleic acids necessary for the replication of the genome?
Signup and view all the answers
Which enzyme is responsible for transferring the formyl group from N10-formyltetrahydrofolate to glycine in the purine biosynthesis pathway?
Which enzyme is responsible for transferring the formyl group from N10-formyltetrahydrofolate to glycine in the purine biosynthesis pathway?
Signup and view all the answers
Which molecule is required for the substitution of NH3 for the C=O oxygen atom at C-6 in the synthesis of adenylate from inosinate?
Which molecule is required for the substitution of NH3 for the C=O oxygen atom at C-6 in the synthesis of adenylate from inosinate?
Signup and view all the answers
Which enzyme catalyzes the removal of fumarate from 5-aminoimidazole-4-N-succinocarboxamide ribonucleotide in the synthesis of inosinate?
Which enzyme catalyzes the removal of fumarate from 5-aminoimidazole-4-N-succinocarboxamide ribonucleotide in the synthesis of inosinate?
Signup and view all the answers
Study Notes
Nucleotide Biosynthesis and Purine Biosynthesis
- Purine base is synthesized directly onto a ribose-based structure in ten metabolic steps, with inosine 5’-monophosphate (IMP) as the common precursor for AMP and GMP
- The synthesis of purine nucleotides is expensive, utilizing the equivalent of 6 moles of ATP per mole of IMP synthesized
- All enzymes involved in the synthesis of purine nucleotides are found in the cytosol of the cell
- Mutations in the X-linked recessive PRPP SYNTHASE/RPDPKINASE lead to purine and uric acid overproduction, causing conditions like gout and sensorineural hearing loss
- The enzyme Glutamine phosphoribosyl amidotransferase catalyzes the committed step in purine biosynthesis, forming the N-glycosidic bond of the purine nucleotide
- Purine biosynthesis enzyme comprises two domains, with the second producing NH3 from glutamine by hydrolysis
- Azaserine and 6-diazo-5-oxo-norleucine are purine antagonists with antineoplastic and antibiotic properties, inhibiting amidotransferases
- The next six steps in purine biosynthesis involve the activation of a carbon-bound oxygen atom by phosphorylation, followed by the displacement of a phosphoryl group by NH3 or an R-NH3 group
- Tetrahydrofolate, a carrier of activated one-carbon units, is obtained from diets or microorganisms in intestinal tracts, and its deficiency is linked to megaloblastic anemia
- Trimethoprim, a folate analog, selectively inhibits bacterial dihydrofolate reductase and has potent antibacterial activity
- Methotrexate, a structural analog of folic acid, is used to control cancer spread by interfering with nucleotides for DNA and RNA, with toxic effects on rapidly replicating cells
- Normal cells can be rescued from the toxic effects of methotrexate by N5formylH folate (leucovorin), which acts as a synthetic inhibitor of purine synthesis
Purine Nucleotide Metabolism and Immunodeficiency Diseases
- De novo formation of GMP is blocked, affecting T and B cells by depriving them of a key component of nucleic acids
- NMPs are converted to NDP and NTP by base-specific kinases, using ATP as the phosphate source
- Adenylate kinase is particularly active in high energy turnover tissues like liver and muscle
- Glutathione and Thioredoxin serve as reductants for ribonucleotide reductase
- DeoxyATP, dGTP, and dTTP inhibit reduction of specific substrates, impacting DNA synthesis
- Hydroxyurea and tiazofurin are inhibitors of ribonucleotide reductase, affecting DNA synthesis
- Adenosine deaminase deficiency leads to a buildup of dATP, inhibiting ribonucleotide reductase and DNA synthesis
- Purine nucleoside phosphorylase (PNP-deficiency) leads to T-cell toxicity due to elevated dGTP levels
- Pentostatin is a potent inhibitor of ADA, mimicking genetic ADA deficiency and affecting T- and B-cell functions
- Cladribine, a purine analog, causes DNA strand breaks and apoptosis, depleting NAD and ATP
- Allopurinol is used to treat gout by inhibiting xanthine oxidase and decreasing uric acid levels
- Salvage pathways for purine bases and nucleosides economize intracellular energy expenditure and are regulated by end products of the reactions
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Description
Test your knowledge of nucleotide biosynthesis with this quiz. Explore the activated precursors of nucleic acids, their role in genome replication, transcription, and energy production, as well as their function as phosphoryl group donors and allosteric effectors.
