Biochemistry Nucleotide Metabolism Part 2

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?

It directly produces uric acid through de novo synthesis Signup and view all the answers

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

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

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

Elevated levels of plasma uric acid Signup and view all the answers

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

Decreased salvage of hypoxanthine and guanine Signup and view all the answers

What is a characteristic feature of secondary hyperuricemia?

It involves increased availability of purine nucleotides. Signup and view all the answers

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

Carbamoyl phosphate synthetase Signup and view all the answers

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

It increases PRPP production efficiency. Signup and view all the answers

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

Decreased uric acid production Signup and view all the answers

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

Increased PRPP availability Signup and view all the answers

How does ADA deficiency affect nucleotide metabolism?

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

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

Severe combined immunodeficiency disease Signup and view all the answers

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

Inhibition of deoxyribose-containing nucleotide production Signup and view all the answers

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

Orotate decarboxylase Signup and view all the answers

What genetic defect is associated with orotic aciduria?

Deficiency of one or both activities of UMP synthase Signup and view all the answers

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

PRPP Signup and view all the answers

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

Developmental arrest and apoptosis Signup and view all the answers

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

Uridine monophosphate (UMP) Signup and view all the answers

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

Carbamoyl phosphate synthetase II Signup and view all the answers

What is one common outcome of purine nucleoside phosphorylase deficiency?

Less severe complications than ADA deficiency Signup and view all the answers

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

It inhibits the enzyme. Signup and view all the answers

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

Glutamine Signup and view all the answers

Which statement is true regarding the synthesis of orotic acid?

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

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

Bone marrow transplant Signup and view all the answers

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

CTP synthetase Signup and view all the answers

What is the consequence of a defect in ornithine transcarbamylase?

It promotes pyrimidine synthesis. Signup and view all the answers

Where is dihydroorotate dehydrogenase located within the cell?

Inner mitochondrial membrane Signup and view all the answers

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

dCTP Signup and view all the answers

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

CPS II, aspartate transcarbamoylase, and dihydroorotase Signup and view all the answers

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

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

What class of compounds does 5-fluorouracil belong to?

Thymine analogs Signup and view all the answers

How does methotrexate affect nucleotide metabolism?

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

What is produced from the degradation of pyrimidine nucleotides?

β-alanine and β-aminoisobutyrate Signup and view all the answers

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

Dihydrofolate reductase Signup and view all the answers

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

N5,N10-methylene tetrahydrofolate Signup and view all the answers

What causes 5-FdUMP to permanently inactivate thymidylate synthase?

It forms a covalent bond with the enzyme. Signup and view all the answers

Which enzyme utilizes ATP to convert nucleosides into nucleotides?

Nucleotide kinases 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.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

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.

Biochemistry Nucleotide Metabolism Part 2

Questions and Answers

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

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

What effect does lactic acidosis have on uric acid excretion?

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

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

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

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

What is a characteristic feature of secondary hyperuricemia?

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

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

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

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

How does ADA deficiency affect nucleotide metabolism?

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

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

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

What genetic defect is associated with orotic aciduria?

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

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

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

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

What is one common outcome of purine nucleoside phosphorylase deficiency?

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

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

Which statement is true regarding the synthesis of orotic acid?

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

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

What is the consequence of a defect in ornithine transcarbamylase?

Where is dihydroorotate dehydrogenase located within the cell?

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

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

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

What class of compounds does 5-fluorouracil belong to?

How does methotrexate affect nucleotide metabolism?

What is produced from the degradation of pyrimidine nucleotides?

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

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

What causes 5-FdUMP to permanently inactivate thymidylate synthase?

Which enzyme utilizes ATP to convert nucleosides into nucleotides?

Study Notes

Purine Nucleotide Degradation

Adenosine Deaminase (ADA) Deficiency

Pyrimidine Synthesis and Degradation

Synthesis of TMP from dUMP

Pyrimidine Salvage and Degradation

Studying That Suits You

Description

More Quizzes Like This

Biochemistry 11: Nucleotide Metabolism and Associated Diseases Quiz

Nucleotide Synthesis and Metabolism

Degradación de purinas: Paso a paso

Biochemistry Nucleotide Metabolism Part 2