Nucleotide Degradation and Salvage Pathways — MCQs
Gout results due to defective function of the following enzyme:
Which of the following statements about carbamoyl phosphate synthase is incorrect?
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?
What is the mechanism of action of colchicine in acute gout?
A 6 year old male child presented with deterioration of renal functions. On examination, he is mentally retarded and has got athetosis. There are multiple healed wounds on his body. His mother reassures you that it was as a result of self inflicted injuries. USG showed bilateral renal calculi. Which of the following statements is FALSE regarding the above mentioned condition?
A patient presented to the emergency department with nausea and vomiting, and intravenous glucose was given, resulting in the patient's recovery. After a few months, the patient presented with the same complaints. Blood glutamine was found to be increased, and orotic acid levels were also raised. What is the diagnosis?
What is the role of adenine phosphoribosyl transferase (APRT) in purine metabolism?
Which of the following organs does not primarily utilize the salvage pathway of purine nucleotide synthesis?
If a sequence of 4 nucleotides codes for 1 amino acid, how many amino acids can be theoretically formed?
Nucleotide Degradation and Salvage Pathways Indian Medical PG Practice Questions and MCQs
Question 1: Gout results due to defective function of the following enzyme:
- A. Glucose 6 phosphatase (Correct Answer)
- B. Glucose 6 phosphate dehydrogenase
- C. PRPP synthetase
- D. Purine nucleotide phosphorylase
Explanation: ***Glucose 6 phosphatase*** - Deficiency of **glucose-6-phosphatase** causes **glycogen storage disease type I** (von Gierke disease), which leads to **secondary hyperuricemia** and recurrent **gout attacks**. - The mechanism involves impaired **gluconeogenesis** and **glycogenolysis**, causing increased production of **lactate** (which competes with uric acid for renal excretion) and accelerated **purine nucleotide degradation** to uric acid. - This is the **most common enzyme deficiency** among the options that results in gout as a clinical manifestation. *Glucose 6 phosphate dehydrogenase* - Deficiency of **G6PD** primarily causes **hemolytic anemia** due to oxidative stress on red blood cells, not gout. - It is crucial for the **pentose phosphate pathway** generating NADPH, but does not directly affect purine or uric acid metabolism. *PRPP synthetase* - **Overactivity** (gain-of-function mutation) of **PRPP synthetase** leads to gout through increased purine synthesis. - However, **defective function** (as stated in the question) would actually **decrease** purine synthesis and **lower** uric acid levels, not cause gout. - This is not the correct answer since the question specifically asks for "defective function." *Purine nucleotide phosphorylase* - Deficiency of **purine nucleoside phosphorylase** (PNP) causes severe **T-cell immunodeficiency**, not gout. - While it affects purine metabolism, the accumulated metabolites are immunotoxic rather than causing hyperuricemia and gout.
Question 2: Which of the following statements about carbamoyl phosphate synthase is incorrect?
- A. Requires biotin as a cofactor (Correct Answer)
- B. Enzyme found in the cytosol
- C. Enzyme found in mitochondria
- D. Catalyzes a condensation reaction
Explanation: ***Requires biotin as a cofactor*** - This is the **incorrect** statement and therefore the correct answer to this question. - Carbamoyl phosphate synthase (both CPS I and CPS II) does **NOT require biotin** as a cofactor. - Biotin is a cofactor for **carboxylase enzymes** such as pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase, and methylcrotonyl-CoA carboxylase. - Carbamoyl phosphate synthase requires **ATP** and **Mg²⁺** but not biotin. *Enzyme found in mitochondria* - This statement is **correct**. - **Carbamoyl phosphate synthase I (CPS I)** is located in the **mitochondrial matrix** and catalyzes the first step of the urea cycle. - CPS I uses free ammonia (NH₃) as the nitrogen source and is activated by N-acetylglutamate. *Enzyme found in the cytosol* - This statement is **correct**. - **Carbamoyl phosphate synthase II (CPS II)** is located in the **cytosol** and is involved in de novo pyrimidine biosynthesis. - CPS II uses the amide nitrogen of glutamine (not free ammonia) as the nitrogen source. *Catalyzes a condensation reaction* - This statement is **correct**. - Both CPS I and CPS II catalyze the condensation of CO₂ (as bicarbonate), ammonia/glutamine, and two molecules of ATP to form carbamoyl phosphate, 2 ADP, and inorganic phosphate. - This is a complex reaction involving phosphorylation and condensation steps.
Question 3: 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 4: 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 5: What is the mechanism of action of colchicine in acute gout?
- A. Renal disease involving interstitial tissues
- B. Uric acid nephrolithiasis
- C. Deficiency of enzyme Xanthine oxidase
- D. Inhibition of leukocyte migration and phagocytosis (Correct Answer)
Explanation: ***Inhibition of leukocyte migration and phagocytosis*** - Colchicine primarily exerts its anti-inflammatory effect in acute gout by **binding to tubulin**, which inhibits microtubule polymerization. - This action disrupts essential cellular functions in inflammatory cells, particularly **neutrophils**, thereby reducing their migration to inflamed sites and their ability to phagocytose uric acid crystals. *Renal disease involving interstitial tissues* - This option describes a potential complication or manifestation of gout, such as **urate nephropathy**, rather than the mechanism of action of colchicine. - Colchicine does not directly target or treat pre-existing renal interstitial tissue disease as its primary mechanism for acute gout relief. *Uric acid nephrolithiasis* - This condition involves the formation of **kidney stones from uric acid** and is a consequence of chronic hyperuricemia. - Colchicine is not used to acutely treat or prevent the formation of uric acid kidney stones; its role is in managing the inflammatory arthritis of gout. *Deficiency of enzyme Xanthine oxidase* - **Xanthine oxidase** is an enzyme involved in the production of uric acid, and its inhibition (e.g., by allopurinol or febuxostat) is a strategy to lower uric acid levels in the blood. - Colchicine does not affect xanthine oxidase activity; it works downstream by modulating the inflammatory response to uric acid crystals.
Question 6: A 6 year old male child presented with deterioration of renal functions. On examination, he is mentally retarded and has got athetosis. There are multiple healed wounds on his body. His mother reassures you that it was as a result of self inflicted injuries. USG showed bilateral renal calculi. Which of the following statements is FALSE regarding the above mentioned condition?
- A. Allopurinol may be used in treating the condition
- B. Kelley - Seegmiller syndrome is a milder variant of the condition
- C. Hyperuricemia is a characteristic feature of the condition
- D. It is an autosomal recessive condition (Correct Answer)
- E. HGPRT enzyme deficiency is the underlying biochemical defect
Explanation: ***It is an autosomal recessive condition*** - **Lesch-Nyhan syndrome** is an **X-linked recessive disorder**, meaning it primarily affects males and is inherited through the mother. - The gene responsible for **hypoxanthine-guanine phosphoribosyltransferase (HGPRT)** deficiency is located on the X chromosome. *Allopurinol may be used in treating the condition* - **Allopurinol** can be used to treat the **hyperuricemia** and prevent **renal calculi** and **gout** in patients with Lesch-Nyhan syndrome. - It works by inhibiting **xanthine oxidase**, thereby reducing uric acid production. *Kelley - Seegmiller syndrome is a milder variant of the condition* - **Kelley-Seegmiller syndrome** is indeed a milder variant of **Lesch-Nyhan syndrome**, characterized by partial rather than complete deficiency of **HGPRT** activity. - Patients with Kelley-Seegmiller syndrome typically present with **hyperuricemia** and **gout-like symptoms** but without the severe neurological manifestations such as **cognitive impairment** and **self-mutilation**. *Hyperuricemia is a characteristic feature of the condition* - **Hyperuricemia** is a hallmark feature of **Lesch-Nyhan syndrome** due to the deficiency of **HGPRT**, leading to overproduction and decreased salvage of purines. - This elevated uric acid level can cause **gouty arthritis** and **renal calculi**, contributing to renal dysfunction. *HGPRT enzyme deficiency is the underlying biochemical defect* - **Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)** deficiency is the fundamental enzyme defect in **Lesch-Nyhan syndrome**. - This enzyme is crucial for the **purine salvage pathway**, and its absence leads to overproduction of uric acid and accumulation of purine precursors that contribute to the neurological manifestations.
Question 7: A patient presented to the emergency department with nausea and vomiting, and intravenous glucose was given, resulting in the patient's recovery. After a few months, the patient presented with the same complaints. Blood glutamine was found to be increased, and orotic acid levels were also raised. What is the diagnosis?
- A. CPS-I deficiency
- B. Ornithine transcarbamoylase deficiency (Correct Answer)
- C. CPS-II deficiency
- D. Argininosuccinate synthetase deficiency
Explanation: ***Ornithine transcarbamoylase deficiency*** - **Ornithine transcarbamoylase (OTC) deficiency** leads to the accumulation of **carbamoyl phosphate**, which is shunted into pyrimidine synthesis, causing elevated **orotic acid** levels. - The elevated **glutamine** and the presentation of nausea and vomiting, responsive to glucose, suggest **hyperammonemia**, which is characteristic of OTC deficiency. *CPS-I deficiency* - **Carbamoyl phosphate synthetase I (CPS-I) deficiency** leads to a block in the first step of the urea cycle, causing **hyperammonemia**, but **without elevated orotic acid** because carbamoyl phosphate is not produced. - While patients would present with similar symptoms of **hyperammonemia**, the absence of **orotic aciduria** differentiates it from OTC deficiency. *CPS-II deficiency* - **Carbamoyl phosphate synthetase II (CPS-II)** is involved in **pyrimidine synthesis**, not the urea cycle. A deficiency here would not typically cause **hyperammonemia** or significant urea cycle dysfunction. - Instead, it would primarily affect pyrimidine production and might lead to megaloblastic anemia, which is not indicated here. *Argininosuccinate synthetase deficiency* - **Argininosuccinate synthetase deficiency** (citrullinemia type I) causes accumulation of **citrulline** and **hyperammonemia**. - This condition is characterized by very high plasma **citrulline** levels and does not typically present with elevated **orotic acid** alone as the primary distinguishing metabolic marker.
Question 8: What is the role of adenine phosphoribosyl transferase (APRT) in purine metabolism?
- A. Breakdown of purines
- B. Salvage pathway of purine nucleotide synthesis (Correct Answer)
- C. Not involved in purine metabolism
- D. De novo synthesis of purines
Explanation: ***Salvage pathway of purine nucleotide synthesis*** - **Adenine phosphoribosyl transferase (APRT)** catalyzes the reaction of **adenine** with **5-phosphoribosyl-1-pyrophosphate (PRPP)** to form **adenosine monophosphate (AMP)**. - This reaction is a crucial step in the **purine salvage pathway**, which reclaims pre-formed purine bases and converts them back into nucleotides, conserving energy. *Breakdown of purines* - The breakdown of purines (catabolism) typically involves enzymes like **adenosine deaminase** and **xanthine oxidase**, leading to the formation of **uric acid**. - APRT is involved in synthesizing nucleotides, not their degradation. *Not involved in purine metabolism* - APRT is an enzyme specifically involved in the **anabolic processes** of purine metabolism, as it contributes to the formation of purine nucleotides. - Its role is well-established within the **salvage pathway**. *De novo synthesis of purines* - The **de novo synthesis pathway** builds purine nucleotides from simpler precursors like **amino acids**, **CO2**, and **THF derivatives**. - While both pathways produce purine nucleotides, APRT is exclusively part of the **salvage pathway**, which recycles existing purine bases.
Question 9: 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.
Question 10: If a sequence of 4 nucleotides codes for 1 amino acid, how many amino acids can be theoretically formed?
- A. 4
- B. 64
- C. 16
- D. 256 (Correct Answer)
Explanation: ***256*** - With **4 distinct nucleotides** and a code sequence of **4 nucleotides** per amino acid, the number of possible unique combinations is calculated as 4^4. - This results in 4 × 4 × 4 × 4 = **256 theoretically possible amino acids**. - This is a mathematical combinatorics calculation: with 4 choices at each of 4 positions, total combinations = 4^4 = 256. *64* - This number represents the combinations if **3 nucleotides** coded for one amino acid (4^3 = 64), which is the actual case in the **standard genetic code** (triplet codons). - However, the question specifies a hypothetical sequence of **4 nucleotides** per amino acid, making this option incorrect. *16* - This number would be correct if **2 nucleotides** coded for one amino acid (4^2 = 16). - The problem explicitly states that **4 nucleotides** code for each amino acid in this theoretical scenario. *4* - This would only be the case if each **single nucleotide** coded for one amino acid (4^1 = 4). - Given **4 distinct nucleotides** and a sequence length of 4, the potential for combinations is much higher.
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