Purine Metabolism and Disorders — MCQs
For the conversion of aspartate to asparagine, nitrogen comes from which source?
Mechanism of action of allopurinol is
Which of the following increases uric acid excretion?
A 5-year-old presents with intellectual disability, self-mutilation, and hyperuricemia. What enzyme defect is most likely?
A patient presents with hyperuricemia and gout. Which enzyme's overactivity is most likely associated?
Which molecule provides nitrogen-9 to the purine ring?
The patient shown here is suffering from deficiency of which enzyme?
Inosinic acid is biological precursor of ?
What is mechanism of action of colchicine in acute gout?
Which of the following organs does not primarily utilize the salvage pathway of purine nucleotide synthesis?
Purine Metabolism and Disorders Indian Medical PG Practice Questions and MCQs
Question 1: For the conversion of aspartate to asparagine, nitrogen comes from which source?
- A. Alanine
- B. Glutamate
- C. Glutamine (Correct Answer)
- D. Histidine
Explanation: ***Glutamine*** - The biosynthesis of **asparagine** from **aspartate** is catalyzed by **asparagine synthetase**. - This enzyme utilizes **ATP** and **glutamine** as the amino group donor, with glutamine being hydrolyzed to **glutamate**. *Alanine* - **Alanine** is primarily involved in the **glucose-alanine cycle** for transporting nitrogen from muscle to liver. - It does not directly donate its amino group for the synthesis of asparagine. *Glutamate* - While **glutamate** is a precursor for glutamine, it does not directly donate an amino group in the conversion of aspartate to asparagine. - Glutamate acts as a general amino group donor in many transamination reactions, but not in this specific amidation. *Histidine* - **Histidine** is an essential amino acid involved in various metabolic roles, including acting as a precursor for histamine. - It is not a donor of nitrogen for the biosynthesis of asparagine from aspartate.
Question 2: Mechanism of action of allopurinol is
- A. Recombinant uricase
- B. Decrease chemotaxis
- C. Increase uric acid excretion
- D. Xanthine oxidase inhibition (Correct Answer)
Explanation: ***Xanthine oxidase inhibition*** - **Allopurinol** acts as a **structural analog of hypoxanthine** and competitively inhibits the enzyme **xanthine oxidase**. - By inhibiting **xanthine oxidase**, allopurinol prevents the conversion of hypoxanthine to xanthine and then to uric acid, thereby **decreasing uric acid production**. *Recombinant uricase* - **Recombinant uricase** (e.g., rasburicase, pegloticase) is an enzyme that catalyzes the breakdown of existing uric acid into allantoin, a more soluble compound. - This mechanism is distinct from allopurinol, which **prevents uric acid formation**. *Decrease chemotaxis* - Medications that **decrease chemotaxis**, such as **colchicine**, work by interfering with the migration of neutrophils to sites of inflammation, which is useful in acute gout flares. - This is an **anti-inflammatory mechanism**, not related to uric acid synthesis or excretion. *Increase uric acid excretion* - Drugs that **increase uric acid excretion** are known as **uricosurics** (e.g., probenecid, lesinurad). - These agents act on the renal tubules to **inhibit uric acid reabsorption**, thus promoting its elimination from the body.
Question 3: Which of the following increases uric acid excretion?
- A. Probenecid (Correct Answer)
- B. Allopurinol
- C. Aspirin
- D. Colchicine
Explanation: **Probenecid** - **Probenecid** is a **uricosuric agent** that increases renal excretion of uric acid by inhibiting its reabsorption in the proximal tubule. - It is used in the treatment of **chronic gout** to lower serum uric acid levels. *Allopurinol* - **Allopurinol** works by inhibiting **xanthine oxidase**, an enzyme responsible for uric acid synthesis, thereby reducing its production. - It does not increase uric acid excretion but rather decreases its formation, making it suitable for **overproducers** of uric acid. *Aspirin* - **Low-dose aspirin** can actually *decrease* uric acid excretion by interfering with tubular secretion of uric acid. - **High-dose aspirin** has a uricosuric effect, but it is not typically used for gout due to side effects and more effective alternatives. *Colchicine* - **Colchicine** is an **anti-inflammatory agent** used to treat acute gout flares by inhibiting neutrophil chemotaxis and activation. - It does **not affect uric acid synthesis or excretion** directly, but rather mitigates the inflammatory response to uric acid crystals.
Question 4: A 5-year-old presents with intellectual disability, self-mutilation, and hyperuricemia. What enzyme defect is most likely?
- A. Adenosine deaminase deficiency
- B. Xanthine oxidase deficiency
- C. Glucose-6-phosphatase deficiency
- D. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) (Correct Answer)
Explanation: ***Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)*** - Deficiency of **HGPRT** an enzyme in the **purine salvage pathway** leads to **Lesch-Nyhan syndrome**, characterized by **hyperuricemia**, **self-mutilation**, **intellectual disability**, and **dystonia**. - The accumulation of **uric acid** due to defective salvage leads to the characteristic symptoms. *Adenosine deaminase deficiency* - This deficiency causes **severe combined immunodeficiency (SCID)** due to the accumulation of toxic metabolites in lymphocytes. - It does not typically present with **self-mutilation** or **hyperuricemia**. *Xanthine oxidase deficiency* - This deficiency leads to **xanthinuria**, characterized by **low uric acid levels** and an increased risk of **xanthine kidney stones**. - The clinical presentation does not include **intellectual disability** or **self-mutilation**. *Glucose-6-phosphatase deficiency* - This enzyme deficiency causes **Glycogen Storage Disease Type Ia (von Gierke disease)**, characterized by **hypoglycemia**, **lactic acidosis**, and **hepatomegaly**. - It is not associated with **self-mutilation** or the primary neurological/behavioral features seen in Lesch-Nyhan syndrome.
Question 5: A patient presents with hyperuricemia and gout. Which enzyme's overactivity is most likely associated?
- A. HGPRT
- B. Xanthine oxidase
- C. Adenosine deaminase
- D. PRPP synthetase (Correct Answer)
Explanation: ***PRPP synthetase*** - **Overactivity** of **PRPP synthetase** leads to increased production of **5-phosphoribosyl-1-pyrophosphate (PRPP)**, a key substrate for *de novo* purine synthesis. - This increased purine synthesis results in an **overproduction of uric acid**, causing **hyperuricemia** and **gout**. *HGPRT* - **Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)** deficiency, not overactivity, is associated with hyperuricemia and gout, as seen in **Lesch-Nyhan syndrome**. - Its normal function is in the **salvage pathway**, recycling purine bases; deficiency leads to increased *de novo* purine synthesis. *Xanthine oxidase* - **Xanthine oxidase** is involved in the catabolism of purines, converting **hypoxanthine to xanthine** and then **xanthine to uric acid**. - While inhibition of this enzyme (e.g., by allopurinol) is a treatment for gout, its **overactivity alone is not typically the primary cause** of hereditary hyperuricemia; rather, altered purine metabolism leading to excess substrates for xanthine oxidase is the issue. *Adenosine deaminase* - Deficiency of **adenosine deaminase (ADA)** is primarily associated with **severe combined immunodeficiency (SCID)**, due to the accumulation of toxic metabolites that impair lymphocyte development. - It is not directly linked to the pathogenesis of **hyperuricemia** or **gout**.
Question 6: Which molecule provides nitrogen-9 to the purine ring?
- A. Glycine (Correct Answer)
- B. Glutamine
- C. CO2
- D. Aspartate
Explanation: ***Glycine*** - Glycine provides the **amino nitrogen at position 9** (N-9) of the purine ring. - It also contributes **carbon atoms at positions 4 and 5** (C-4, C-5) and the **nitrogen at position 7** (N-7). - Glycine is incorporated as an intact molecule early in purine synthesis, forming the **glycinamide ribonucleotide** intermediate. *Glutamine* - The **amide nitrogen** of glutamine donates nitrogen atoms at **positions 3 only** (N-3), not position 9. - This donation occurs during the formation of **formylglycinamide ribonucleotide** (FGAR) from FGAM. - Glutamine contributes two amide nitrogen atoms during purine synthesis, but N-9 is not one of them. *Aspartate* - Aspartate contributes the **nitrogen atom at position 1** (N-1) of the purine ring. - It is incorporated into the intermediate **5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide** (SACAIR). - The nitrogen from aspartate remains after fumarate is released. *CO2* - Carbon dioxide (CO2) contributes the **carbon atom at position 6** (C-6) of the purine ring. - It provides a **carbon source** for ring formation, not nitrogen atoms. - CO2 is incorporated during the carboxylation step in the purine biosynthetic pathway.
Question 7: The patient shown here is suffering from deficiency of which enzyme?
- A. Xanthine oxidase
- B. HGPRTase (Correct Answer)
- C. Glucose-6-phosphate dehydrogenase
- D. Adenosine deaminase
Explanation: ***HGPRTase*** - **HGPRTase deficiency** causes **Lesch-Nyhan syndrome** with characteristic **self-mutilation behavior**, choreoathetosis, and severe intellectual disability. - Clinical features include **orange sand-like crystals** in diapers due to hyperuricemia, **compulsive self-biting**, and **dystonia** as shown in the patient. *Adenosine deaminase* - **ADA deficiency** causes **SCID** with recurrent infections, lymphopenia, and failure to thrive in early infancy. - Clinical presentation focuses on **immunodeficiency** with chronic infections rather than neurological and behavioral abnormalities. *Xanthine oxidase* - **Xanthine oxidase deficiency** leads to **xanthinuria** with accumulation of xanthine causing kidney stones. - Patients present with **nephrolithiasis** and muscle pain but lack the neurological and self-destructive behaviors seen here. *Glucose-6-phosphate dehydrogenase* - **G6PD deficiency** causes **hemolytic anemia** triggered by oxidative stress from drugs, infections, or fava beans. - Features include **jaundice**, dark urine, and acute hemolysis but not the characteristic **neurological dysfunction** and **self-mutilation** of Lesch-Nyhan syndrome.
Question 8: Inosinic acid is biological precursor of ?
- A. Purines and thymine
- B. Orotic acid and uridylic acid
- C. Adenylic acid and guanylic acid (Correct Answer)
- D. Uracil and thymine
Explanation: ***Adenylic acid and guanylic acid*** - Inosinic acid (IMP) is a **key intermediate** in the **de novo purine synthesis pathway**. - It serves as the direct precursor for the synthesis of **adenylic acid (AMP)** and **guanylic acid (GMP)**, which are components of DNA and RNA. *Purines and thymine* - While inosinic acid is a precursor to purines, it is **not a precursor to thymine**. - Thymine is a **pyrimidine base** and is synthesized through a separate pathway. *Orotic acid and uridylic acid* - **Orotic acid** is an intermediate in **pyrimidine synthesis**, not purine synthesis. - **Uridylic acid (UMP)** is also a pyrimidine nucleotide, and its synthesis pathway involves orotic acid, not inosinic acid. *Uracil and thymine* - **Uracil** and **thymine** are pyrimidine bases, and their synthesis pathways are distinct from the purine synthesis pathway involving inosinic acid. - Inosinic acid is exclusively involved in the synthesis of **purine nucleotides**.
Question 9: What is mechanism of action of colchicine in acute gout?
- A. Inhibition of purine metabolism
- B. Inhibition of uric acid conversion
- C. Migration of leukocytes
- D. Inhibition of leukocyte migration and microtubule function (Correct Answer)
Explanation: ***Inhibition of leukocyte migration and microtubule function*** - Colchicine works by disrupting **microtubule polymerization**, which interferes with the **motility and activity of neutrophils and other inflammatory cells** [1]. - Its anti-inflammatory effect in acute gout is primarily due to the inhibition of **leukocyte migration and phagocytosis of urate crystals**, thereby reducing the inflammatory response [1]. - The mechanism involves binding to **tubulin**, preventing microtubule assembly, which affects multiple cellular processes including chemotaxis and cell division [1]. *Inhibition of purine metabolism* - This mechanism is associated with drugs like **allopurinol**, which inhibit **xanthine oxidase** to reduce uric acid production [2]. - Colchicine does not directly inhibit **purine metabolism** or uric acid synthesis; its effect is on the inflammatory response, not uric acid formation [1]. *Inhibition of uric acid conversion* - This mechanism refers to **uricosuric agents** like probenecid that increase renal excretion of uric acid. - Colchicine's action is primarily anti-inflammatory, not related to uric acid metabolism or excretion [1]. *Migration of leukocytes* - While this is partially correct, as colchicine does inhibit **leukocyte migration**, this option is incomplete. - The complete mechanism must include its action as a **microtubule inhibitor**, which is the underlying basis for all its cellular effects including inhibition of migration, phagocytosis, and inflammatory mediator release [1].
Question 10: Which of the following organs does not primarily utilize the salvage pathway of purine nucleotide synthesis?
- A. RBC
- B. Leukocytes
- C. Liver (Correct Answer)
- D. Brain
Explanation: ***Liver*** - The **liver** is capable of both *de novo* synthesis and the salvage pathway of purine nucleotides, but it primarily utilizes the **de novo pathway** due to its high metabolic capacity and central role in biosynthesis for the entire body. - While salvage pathways exist, the liver's robust *de novo* synthesis allows it to readily produce purines from simple precursors, making it less reliant on salvaging pre-formed bases. *Brain* - The **brain** relies heavily on the **salvage pathway** for purine nucleotide synthesis because it has a limited capacity for *de novo* purine synthesis. - This dependency makes the brain particularly vulnerable to deficiencies in salvage enzymes, such as in **Lesch-Nyhan syndrome** where HGPRT deficiency leads to severe neurological dysfunction. *RBC* - **Red blood cells (RBCs)** are anucleated and lack the machinery for *de novo* purine synthesis, making them entirely dependent on the **salvage pathway** to maintain their purine nucleotide pool. - They salvage pre-formed purine bases and nucleosides from the plasma to synthesize necessary adenine and guanine nucleotides. *Leukocytes* - **Leukocytes**, particularly lymphocytes, have a high turn-over rate and metabolic activity, and they primarily rely on the **salvage pathway** for purine nucleotide synthesis. - The **immune system's rapid proliferation** and response demand efficient nucleotide synthesis, and the salvage pathway offers a quick and energy-efficient way to achieve this.
Want unlimited practice?
Get full access to all questions, explanations, and performance tracking.
Start For Free