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Questions and Answers
What is a consequence of lactic acidosis on uric acid excretion?
What is a consequence of lactic acidosis on uric acid excretion?
Which of the following correctly describes the role of oxypurinol?
Which of the following correctly describes the role of oxypurinol?
In the context of uric acid metabolism, what is the significance of a normal HGPRT level?
In the context of uric acid metabolism, what is the significance of a normal HGPRT level?
Which drug is known as a non-purine inhibitor of xanthine oxidase?
Which drug is known as a non-purine inhibitor of xanthine oxidase?
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Which of the following is a primary cause of underexcretion of uric acid?
Which of the following is a primary cause of underexcretion of uric acid?
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What is the effect of an X-linked PRPP synthetase mutation on purine production?
What is the effect of an X-linked PRPP synthetase mutation on purine production?
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Which condition is characterized by hyperuricemia due to decreased salvage of hypoxanthine and guanine?
Which condition is characterized by hyperuricemia due to decreased salvage of hypoxanthine and guanine?
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In cases of secondary hyperuricemia, what is a common underlying cause?
In cases of secondary hyperuricemia, what is a common underlying cause?
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What is the primary consequence of increased levels of PRPP in nucleotide metabolism?
What is the primary consequence of increased levels of PRPP in nucleotide metabolism?
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Which of the following is a potential consequence of ADA deficiency?
Which of the following is a potential consequence of ADA deficiency?
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Which process is involved in the synthesis of UTP and CTP?
Which process is involved in the synthesis of UTP and CTP?
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What is the consequence of decreased salvage activity in purine nucleotides?
What is the consequence of decreased salvage activity in purine nucleotides?
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Which of the following statements about pyrimidine metabolism is false?
Which of the following statements about pyrimidine metabolism is false?
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What characterizes gout in relation to purine catabolism?
What characterizes gout in relation to purine catabolism?
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Which of the following is a nonsteroidal anti-inflammatory drug used to treat gout?
Which of the following is a nonsteroidal anti-inflammatory drug used to treat gout?
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What condition arises from the deposition of monosodium urate crystals?
What condition arises from the deposition of monosodium urate crystals?
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How does colchicine function in treating gout?
How does colchicine function in treating gout?
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What diagnostic method is used to confirm the presence of monosodium urate crystals in gout?
What diagnostic method is used to confirm the presence of monosodium urate crystals in gout?
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Which dietary habit is associated with an increased risk of developing gout?
Which dietary habit is associated with an increased risk of developing gout?
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What is the primary purpose of uricosuric agents in gout treatment?
What is the primary purpose of uricosuric agents in gout treatment?
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Which of the following is NOT a characteristic of hyperuricemia?
Which of the following is NOT a characteristic of hyperuricemia?
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What treatment option is often used for underexcretors of uric acid?
What treatment option is often used for underexcretors of uric acid?
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Which of the following conditions is characterized by the increased production of uric acid?
Which of the following conditions is characterized by the increased production of uric acid?
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Which compound acts as a suicide inhibitor of thymidylate synthase?
Which compound acts as a suicide inhibitor of thymidylate synthase?
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What is the primary source of the methyl group in the synthesis of thymidine monophosphate from dUMP?
What is the primary source of the methyl group in the synthesis of thymidine monophosphate from dUMP?
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Which of the following compounds is inhibited by Methotrexate?
Which of the following compounds is inhibited by Methotrexate?
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In the degradation of pyrimidine nucleotides, which of the following is NOT a product?
In the degradation of pyrimidine nucleotides, which of the following is NOT a product?
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What role do nucleotide kinases play in nucleotide metabolism?
What role do nucleotide kinases play in nucleotide metabolism?
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What is a major effect of inhibiting thymidylate synthase?
What is a major effect of inhibiting thymidylate synthase?
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Which molecule is primarily linked to the antibacterial activity of Trimethoprim?
Which molecule is primarily linked to the antibacterial activity of Trimethoprim?
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Which condition is treated with uridine due to its role in nucleotide metabolism?
Which condition is treated with uridine due to its role in nucleotide metabolism?
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What is the role of UTP in the regulation of carbamoyl phosphate synthesis?
What is the role of UTP in the regulation of carbamoyl phosphate synthesis?
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Which enzyme is responsible for the transformation of aspartate into carbamoylaspartate?
Which enzyme is responsible for the transformation of aspartate into carbamoylaspartate?
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What is the function of dihydroorotase in pyrimidine synthesis?
What is the function of dihydroorotase in pyrimidine synthesis?
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How does PRPP affect carbamoyl phosphate synthetase II activity?
How does PRPP affect carbamoyl phosphate synthetase II activity?
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What is the direct precursor of urea in the metabolic pathway discussed?
What is the direct precursor of urea in the metabolic pathway discussed?
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What is the primary role of glutamine in carbamoyl phosphate synthesis?
What is the primary role of glutamine in carbamoyl phosphate synthesis?
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Which of the following enzymes is not involved in the synthesis of UTP and CTP?
Which of the following enzymes is not involved in the synthesis of UTP and CTP?
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Which metabolic step is associated with the formation of orotic acid?
Which metabolic step is associated with the formation of orotic acid?
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Study Notes
Purine Nucleotide Degradation
- X-linked PRPP synthetase mutation increases PRPP levels, enhancing purine production and elevating plasma uric acid.
- Associated diseases include gout and adenosine deaminase (ADA) deficiency.
- Gout results from hyperuricemia, linked to purine overproduction or underexcretion, leading to monosodium urate crystal deposition in joints, soft tissues, and kidneys.
- Dietary factors influence gout risk: high meat/seafood increases risk; low-fat dairy decreases risk.
- Gout treatment includes anti-inflammatory agents (colchicine, prednisone, indomethacin) and uricosuric agents (probenecid, sulfinpyrazone) to lower uric acid levels.
- Allopurinol inhibits uric acid synthesis and promotes hypoxanthine accumulation, which is more soluble and less inflammatory.
Purine Synthesis and Associated Disorders
- Underexcretion of uric acid can be primary (unknown defects) or secondary to other diseases affecting renal handling of urate, like lactic acidosis or drug effects (thiazide diuretics, lead exposure).
- Increased PRPP levels can exacerbate conditions like Lesch-Nyhan syndrome, characterized by hyperuricemia due to decreased salvage of hypoxanthine and guanine.
Pyrimidine Synthesis and Degradation
- Carbamoyl phosphate is synthesized from glutamine and CO2; this step is regulated by CPS II, with UTP inhibiting and PRPP activating the process.
- Synthesis of orotic acid involves the formation of carbamoylaspartate and oxidation to orotic acid through specific enzymes (aspartate transcarbamoylase, dihydroorotase, dihydroorotate dehydrogenase).
- UTP is converted to CTP via amination; ribonucleotide reductase then helps synthesize dCTP for DNA.
Thymidine Synthesis and Regulation
- TMP is synthesized from dUMP, with thymidylate synthase playing a crucial role; it is inhibited by 5-fluorouracil, leading to decreased DNA synthesis.
- Methotrexate inhibits dihydrofolate reductase, reducing THF supply and consequently inhibiting purine and TMP synthesis, slowing cell growth.
Pyrimidine Salvage and Degradation
- Salvage pathways involve nucleotide kinases utilizing ATP for nucleoside phosphorylation; uridine is beneficial in hereditary orotic aciduria treatment.
- Pyrimidine nucleotides degrade into soluble products, including β-alanine, β-aminoisobutyrate, ammonia, and carbon dioxide.
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Description
This quiz covers the degradation of purine nucleotides, including the effects of X-linked PRPP synthetase mutation and its association with elevated plasma uric acid levels. Understand the metabolic pathways and related diseases. Test your knowledge on the complexities of nucleotide metabolism in biochemistry.