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Questions and Answers
What is the product of the phosphorolytic cleavage of guanosine?
What is the product of the phosphorolytic cleavage of guanosine?
- Guanine (correct)
- Inosine
- Xanthine
- Hypoxanthine
What enzyme catalyzes the conversion of guanine to xanthine?
What enzyme catalyzes the conversion of guanine to xanthine?
- Xanthine oxidase
- Adenosine deaminase
- Purine nucleoside phosphorylase
- Guanine deaminase (correct)
Which substance is produced by xanthine oxidase?
Which substance is produced by xanthine oxidase?
- Uric acid (correct)
- Hypoxanthine
- Inosine
- Guanosine
What happens to adenosine during its conversion process?
What happens to adenosine during its conversion process?
What is the role of purine nucleoside phosphorylase in the metabolism of inosine?
What is the role of purine nucleoside phosphorylase in the metabolism of inosine?
Which compound is formed by the removal of the pentose sugars from nucleosides?
Which compound is formed by the removal of the pentose sugars from nucleosides?
What is the overall process that converts adenosine to hypoxanthine?
What is the overall process that converts adenosine to hypoxanthine?
What type of reaction does guanine undergo to convert into uric acid?
What type of reaction does guanine undergo to convert into uric acid?
What is the primary cause of gout in patients with Lesch-Nyhan syndrome?
What is the primary cause of gout in patients with Lesch-Nyhan syndrome?
Which of the following clinical manifestations is typically the first to appear in gout?
Which of the following clinical manifestations is typically the first to appear in gout?
What is the most common joint affected in gout?
What is the most common joint affected in gout?
Elevated levels of which compound are indicative of gout and may be detected in the blood and urine?
Elevated levels of which compound are indicative of gout and may be detected in the blood and urine?
What mechanism primarily contributes to urate crystal formation in the joints?
What mechanism primarily contributes to urate crystal formation in the joints?
What type of inheritance pattern is seen in Lesch-Nyhan syndrome?
What type of inheritance pattern is seen in Lesch-Nyhan syndrome?
What role does the HGPRT enzyme deficiency play in gout pathology?
What role does the HGPRT enzyme deficiency play in gout pathology?
Which joint conditions can result from uncontrolled gout?
Which joint conditions can result from uncontrolled gout?
What is a primary consequence of overproduction of purine nucleotides?
What is a primary consequence of overproduction of purine nucleotides?
Which factor primarily contributes to the development of uric acid crystals in joints?
Which factor primarily contributes to the development of uric acid crystals in joints?
How does the body's saturation level of uric acid affect crystal formation?
How does the body's saturation level of uric acid affect crystal formation?
What could be a cause of decreased uric acid excretion?
What could be a cause of decreased uric acid excretion?
What cellular process leads to hyperuricemia resulting from excessive purine levels?
What cellular process leads to hyperuricemia resulting from excessive purine levels?
Which joint is least likely to be affected by urate crystal deposition?
Which joint is least likely to be affected by urate crystal deposition?
What effect does an increase in GMP, IMP, or AMP have on uric acid levels?
What effect does an increase in GMP, IMP, or AMP have on uric acid levels?
Which process is directly linked to the formation of urate crystals in tissues?
Which process is directly linked to the formation of urate crystals in tissues?
What laboratory test would help in distinguishing orotic aciduria caused by ornithine transcarbamylase deficiency from that caused by uridine monophosphate synthase deficiency?
What laboratory test would help in distinguishing orotic aciduria caused by ornithine transcarbamylase deficiency from that caused by uridine monophosphate synthase deficiency?
Which drug prevents uric acid synthesis by inhibiting the enzyme xanthine oxidase?
Which drug prevents uric acid synthesis by inhibiting the enzyme xanthine oxidase?
Inosinic acid is the biological precursor of which of the following?
Inosinic acid is the biological precursor of which of the following?
What is the probable metabolic defect in gout?
What is the probable metabolic defect in gout?
The synthesis of GMP from IMP requires which combination of components?
The synthesis of GMP from IMP requires which combination of components?
In humans, which of the following is the principal breakdown product of purines?
In humans, which of the following is the principal breakdown product of purines?
Which of the following compounds is directly involved in pyrimidine degradation?
Which of the following compounds is directly involved in pyrimidine degradation?
Which enzyme is responsible for the salvage pathway of purine nucleotides?
Which enzyme is responsible for the salvage pathway of purine nucleotides?
Which biologic processes are purine bases NOT involved in?
Which biologic processes are purine bases NOT involved in?
What is the primary characteristic of synovial fluid in a patient diagnosed with gout?
What is the primary characteristic of synovial fluid in a patient diagnosed with gout?
What role do purines play in cellular signaling?
What role do purines play in cellular signaling?
Where does purine catabolism predominantly occur?
Where does purine catabolism predominantly occur?
What is a major consequence of abnormal purine biosynthesis and degradation?
What is a major consequence of abnormal purine biosynthesis and degradation?
Which purine is mainly associated with energy currency in the cell?
Which purine is mainly associated with energy currency in the cell?
Which condition is characterized by inflammation and crystal deposition in the joints due to purine metabolism issues?
Which condition is characterized by inflammation and crystal deposition in the joints due to purine metabolism issues?
What is the appearance of crystals found in synovial fluid of a gout patient under polarizing microscopy?
What is the appearance of crystals found in synovial fluid of a gout patient under polarizing microscopy?
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Study Notes
Purine Metabolism and Gout
- Guanosine and deoxyguanosine are converted to guanine via phosphorolytic cleavage by purine nucleoside phosphorylase.
- Guanine is transformed into xanthine through the hydrolysis of its amino group by guanine deaminase.
- Xanthine undergoes oxidation to form uric acid, catalyzed by the enzyme xanthine oxidase.
Adenosine Conversion
- Adenosine and deoxyadenosine convert to inosine and deoxyinosine, respectively, catalyzed by adenosine deaminase.
- Inosine and deoxyinosine are further converted to hypoxanthine by purine nucleoside phosphorylase, removing the pentose sugars.
Biological Importance of Purines
- Purine bases are essential for nucleic acids (RNA and DNA), energy currency (ATP), cofactors (NAD, FAD), and cellular signaling (GTP, ATP, adenosine).
- Purines are synthesized de novo or acquired through the diet; their degradation is a natural metabolic process.
Clinical Presentation of Gout
- Gout is characterized by swollen, tender joints, often beginning in the big toe. Mild distress may occur due to pain.
- Synovial fluid analysis reveals negatively birefringent crystals, indicating monosodium urate crystals.
Diagnosis and Pathophysiology
- Elevated uric acid levels, resulting from decreased excretion or increased production, lead to urate crystal precipitation in joints.
- Hyperuricemia causes inflammation and joint pain, often affecting peripheral joints before progressing to polyarthritis.
Causes of Hyperuricemia
- Metabolic abnormalities can cause overproduction of purine nucleotides, which upon degradation lead to hyperuricemia.
- Conditions like Lesch-Nyhan syndrome, characterized by HGPRT deficiency, result in the inability to salvage purines, enhancing gout risk.
Laboratory Diagnosis
- Definitive diagnosis of gout includes detecting urate crystals in synovial fluid obtained through arthrocentesis.
- Increased uric acid levels in blood and urine confirm hyperuricemia.
Additional Clinical Insights
- Gout commonly presents as monoarthritis, particularly affecting the metatarsophalangeal joint (podagra).
- Crystal formation is influenced by body temperature; lower temperatures in extremities facilitate urate precipitation.
Pharmacological Management
- Allopurinol is a medication that inhibits xanthine oxidase, preventing uric acid synthesis.
Key Laboratory Tests and Biochemical Pathways
- Inosinic acid serves as a biological precursor for both adenylic and guanylic acids.
- Metabolic defects in gout typically involve an overproduction of uric acid or defective renal excretion.
- GMP synthesis from IMP requires glutamine, NAD+, and ATP.
Principal Breakdown Products in Humans
- The primary breakdown product of purine metabolism in humans is uric acid.
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