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?
Signup and view all the answers
What is the primary characteristic of primary underexcretion of uric acid?
Signup and view all the answers
What is the primary consequence of increased levels of PRPP due to X-linked PRPP synthetase mutation?
Signup and view all the answers
In Lesch-Nyhan syndrome, which metabolic change primarily contributes to hyperuricemia?
Signup and view all the answers
What is a characteristic feature of secondary hyperuricemia?
Signup and view all the answers
Which enzyme is directly involved in the synthesis of orotic acid during pyrimidine metabolism?
Signup and view all the answers
What effect does a lower Km for ribose 5-phosphate have on PRPP synthetase activity?
Signup and view all the answers
Which of the following is NOT a result of elevated PRPP levels?
Signup and view all the answers
What is one of the key effects of chemotherapy on purine nucleotide metabolism?
Signup and view all the answers
How does ADA deficiency affect nucleotide metabolism?
Signup and view all the answers
Which condition is characterized by an accumulation of adenosine due to ADA deficiency?
Signup and view all the answers
What is the result of an increase in dATP levels within cells?
Signup and view all the answers
Which enzyme is responsible for converting orotidine 5’-monophosphate (OMP) to uridine monophosphate (UMP)?
Signup and view all the answers
What genetic defect is associated with orotic aciduria?
Signup and view all the answers
What primary contributor to nucleotide synthesis is derived from ribose-5-phosphate?
Signup and view all the answers
What is the fate of lymphocytes in the most severe form of severe combined immunodeficiency disease?
Signup and view all the answers
Which pyrimidine nucleotide is formed after the completion of the pyrimidine ring?
Signup and view all the answers
Which enzyme is primarily responsible for the synthesis of carbamoyl phosphate from glutamine and CO2?
Signup and view all the answers
What is one common outcome of purine nucleoside phosphorylase deficiency?
Signup and view all the answers
What role does UTP play in the regulation of carbamoyl phosphate synthetase II?
Signup and view all the answers
Which factor contributes directly to the synthesis of the pyrimidine ring?
Signup and view all the answers
Which statement is true regarding the synthesis of orotic acid?
Signup and view all the answers
What treatment option is generally considered for individuals with severe combined immunodeficiency disease?
Signup and view all the answers
Which enzyme is responsible for the amination of UTP to form CTP?
Signup and view all the answers
What is the consequence of a defect in ornithine transcarbamylase?
Signup and view all the answers
Where is dihydroorotate dehydrogenase located within the cell?
Signup and view all the answers
What is the final product of the enzymatic conversion of dCDP?
Signup and view all the answers
Which combination of enzymes is associated with the multifunctional peptide domain CAD?
Signup and view all the answers
What is the role of thymidylate synthase in the synthesis of dTMP from dUMP?
Signup and view all the answers
What class of compounds does 5-fluorouracil belong to?
Signup and view all the answers
How does methotrexate affect nucleotide metabolism?
Signup and view all the answers
What is produced from the degradation of pyrimidine nucleotides?
Signup and view all the answers
Which enzyme is inhibited by Trimethoprim, leading to its antibacterial effects?
Signup and view all the answers
What is the main source of the methyl group for the conversion of dUMP to dTMP?
Signup and view all the answers
What causes 5-FdUMP to permanently inactivate thymidylate synthase?
Signup and view all the answers
Which enzyme utilizes ATP to convert nucleosides into nucleotides?
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.