Pyrimidine Metabolism and Disorders — MCQs
Which of the following is not a precursor in the synthesis of pyrimidines?
Which of the following metabolic pathways in carbohydrate metabolism is required for the synthesis of nucleic acids?
Inosinic acid is biological precursor of ?
Orotic aciduria is due to deficiency of:
A patient presents with hyperuricemia and gout. Which enzyme's overactivity is most likely associated?
What is the diagnosis in a patient who presents with nausea and vomiting, initially responds to intravenous glucose, but later develops increased blood glutamine and orotic acid levels?
In alkaptonuria, deficiency is:
Final common pathway of metabolism of carbohydrate, lipids, and protein metabolism is?
An infant presents with failure to thrive and recurrent vomiting episodes. Sepsis screen was negative, blood urea is elevated and urine shows high orotic acid level. Which of the following enzyme is absent?
Which of the following reactions is responsible for folate trap?
Pyrimidine Metabolism and Disorders Indian Medical PG Practice Questions and MCQs
Question 1: Which of the following is not a precursor in the synthesis of pyrimidines?
- A. Glutamine
- B. Carbon dioxide (CO2)
- C. Aspartic acid
- D. Thymidine (Correct Answer)
Explanation: ***Thymidine*** - **Thymidine** is a *nucleoside* consisting of deoxyribose and thymine. It is a *product* and a component of DNA, not a precursor in the *de novo synthesis* of pyrimidine bases. - While it can be incorporated into DNA via the *salvage pathway*, it does not serve as an initial building block for the pyrimidine ring itself. *Glutamine* - **Glutamine** provides the **nitrogen atoms** crucial for the formation of the pyrimidine ring, specifically N3 in the pyrimidine base. - It is a key donor of *amino groups* in various anabolic pathways, including nucleotide synthesis. *Carbon dioxide (CO2)* - **Carbon dioxide (CO2)** contributes one of the carbon atoms (C2) to the pyrimidine ring. - It combines with **ammonia** (derived from glutamine) to form **carbamoyl phosphate**, an essential intermediate. *Aspartic acid* - **Aspartic acid** provides four atoms (N1, C4, C5, C6) of the pyrimidine ring. - Its carbon skeleton and amino group are directly incorporated into the pyrimidine structure during the *de novo synthesis* pathway.
Question 2: Which of the following metabolic pathways in carbohydrate metabolism is required for the synthesis of nucleic acids?
- A. Gluconeogenesis
- B. Glycolysis
- C. HMP shunt (Correct Answer)
- D. Glycogenesis
Explanation: ***HMP shunt*** - The **hexose monophosphate (HMP) shunt**, also known as the **pentose phosphate pathway**, is crucial for producing **ribose-5-phosphate**. - **Ribose-5-phosphate** is a direct precursor for the synthesis of **nucleotides** and subsequently **nucleic acids** (DNA and RNA). *Gluconeogenesis* - This pathway is responsible for the synthesis of **glucose from non-carbohydrate precursors**, primarily to maintain blood glucose levels during fasting. - It does not directly produce components needed for nucleic acid synthesis. *Glycolysis* - **Glycolysis** is the metabolic pathway that breaks down **glucose into pyruvate**, generating ATP. - While it produces intermediates, it is not directly involved in creating the specific pentose sugars required for nucleic acids. *Glycogenesis* - **Glycogenesis** is the process of synthesizing **glycogen from glucose** for storage in the liver and muscles. - This pathway is focused on glucose storage and has no direct role in nucleic acid synthesis.
Question 3: 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 4: Orotic aciduria is due to deficiency of:
- A. Ornithine transcarbamylase
- B. UMP synthase (Correct Answer)
- C. Argininosuccinate lyase
- D. Carbamoyl phosphate synthetase I
Explanation: ***UMP synthase*** - **Orotic aciduria** results from a deficiency in **UMP synthase**, a bifunctional enzyme with **orotate phosphoribosyltransferase** and **OMP decarboxylase** activities. - This deficiency leads to an accumulation of **orotic acid** due to the inability to convert **orotate** to **uridine monophosphate (UMP)**, affecting pyrimidine synthesis. *Ornithine transcarbamylase* - Deficiency in **ornithine transcarbamylase (OTC)** causes **hyperammonemia** and increased plasma **glutamine**, as it's involved in the urea cycle. - While it causes elevated **orotic acid**, this accumulation is due to excess **carbamoyl phosphate** shunting to pyrimidine synthesis, not a direct pyrimidine synthesis defect. *Argininosuccinate lyase* - A deficiency in **argininosuccinate lyase** leads to **argininosuccinic aciduria**, characterized by the accumulation of **argininosuccinic acid** and **hyperammonemia**. - This enzyme is also part of the **urea cycle**, and its dysfunction does not directly cause **orotic aciduria** as its primary symptom. *Carbamoyl phosphate synthetase I* - Deficiency of **carbamoyl phosphate synthetase I (CPS1)** results in severe **hyperammonemia** immediately after birth, as it's the first enzyme in the **urea cycle**. - Unlike **OTC deficiency**, CPS1 deficiency typically does not lead to **elevated orotic acid**, because the upstream precursor **carbamoyl phosphate** is not overproduced and shunted to pyrimidine synthesis.
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: What is the diagnosis in a patient who presents with nausea and vomiting, initially responds to intravenous glucose, but later develops increased blood glutamine and orotic acid levels?
- A. CPS-I deficiency
- B. Arginino succinate synthetase deficiency
- C. CPS-II deficiency
- D. Ornithine transcarbamoylase deficiency (Correct Answer)
Explanation: ***Ornithine transcarbamoylase deficiency*** - **Ornithine transcarbamoylase (OTC) deficiency** is an X-linked urea cycle disorder that leads to the accumulation of **carbamoyl phosphate**. - This excess carbamoyl phosphate is shunted into pyrimidine synthesis, resulting in increased **orotic acid** and **glutamine** levels, and symptoms like nausea and vomiting due to hyperammonemia. *CPS-I deficiency* - **Carbamoyl phosphate synthetase I (CPS-I) deficiency** also causes hyperammonemia but does not involve elevated **orotic acid**, as the pathway leading to pyrimidine synthesis is not overstimulated. - This deficiency would present with high ammonia and glutamine levels, but **normal or low orotic acid**. *Arginino succinate synthetase deficiency* - **Argininosuccinate synthetase deficiency** (citrullinemia) is characterized by very high plasma **citrulline** levels, which are not mentioned in this patient's presentation. - While it is a urea cycle disorder causing hyperammonemia, the diagnostic marker of elevated citrulline differentiates it from OTC deficiency. *CPS-II deficiency* - **Carbamoyl phosphate synthetase II (CPS-II)** is involved in *de novo* pyrimidine synthesis and is not part of the urea cycle. - A deficiency in CPS-II would typically lead to **pyrimidine starvation** rather than hyperammonemia or elevated orotic acid.
Question 7: In alkaptonuria, deficiency is:
- A. Phosphofructokinase
- B. HMG CoA reductase
- C. Homogentisate oxidase (Correct Answer)
- D. Xanthine oxidase
Explanation: ***Homogentisate oxidase*** - **Alkaptonuria** is an autosomal recessive disorder caused by a deficiency of the enzyme **homogentisate 1,2-dioxygenase** (also known as homogentisate oxidase). - This enzyme is crucial in the **catabolic pathway of tyrosine**, specifically breaking down **homogentisic acid**. *Phosphofructokinase* - Deficiency of **phosphofructokinase** (PFK) causes **Tarui's disease** (Glycogen Storage Disease Type VII), affecting **glycolysis**. - Symptoms include exercise intolerance, muscle pain, and hemolysis, which are unrelated to alkaptonuria. *HMG CoA reductase* - **HMG-CoA reductase** is the rate-limiting enzyme in **cholesterol biosynthesis**, and its inhibitors (statins) are used to lower cholesterol levels. - Its deficiency is not associated with alkaptonuria. *Xanthine oxidase* - **Xanthine oxidase** is involved in the catabolism of **purines**, converting hypoxanthine to xanthine and then xanthine to uric acid. - Its deficiency causes **xanthinuria**, leading to kidney stones, and it is not associated with alkaptonuria.
Question 8: Final common pathway of metabolism of carbohydrate, lipids, and protein metabolism is?
- A. Gluconeogenesis
- B. TCA (Correct Answer)
- C. HMP pathway
- D. Glycolysis
Explanation: ***TCA (Tricarboxylic Acid Cycle)*** - The **TCA cycle** (also called Krebs cycle or citric acid cycle) is the **final common oxidative pathway** where all three macronutrients converge - **Carbohydrates** → Pyruvate → **Acetyl-CoA** (via pyruvate dehydrogenase) - **Lipids** → Fatty acids → **Acetyl-CoA** (via beta-oxidation) - **Proteins** → Amino acids → **Acetyl-CoA or TCA intermediates** (via deamination/transamination) - Complete oxidation of acetyl-CoA occurs in the TCA cycle, producing **NADH, FADH2, and GTP** for energy production *Gluconeogenesis* - This is a **biosynthetic pathway** that synthesizes glucose from non-carbohydrate precursors (lactate, glycerol, amino acids) - It is an **anabolic process**, not the catabolic final common pathway for energy production from all macronutrients *Glycolysis* - **Carbohydrate-specific pathway** that converts glucose to pyruvate - It is only the initial breakdown pathway for carbohydrates, not the common pathway where lipids and proteins also converge - Pyruvate from glycolysis must enter TCA cycle for complete oxidation *HMP pathway (Pentose Phosphate Pathway)* - Parallel pathway to glycolysis that generates **NADPH** (for biosynthesis and antioxidant defense) and **ribose-5-phosphate** (for nucleotide synthesis) - Processes only **glucose-6-phosphate** from carbohydrate metabolism - Not involved in lipid or protein metabolism integration
Question 9: An infant presents with failure to thrive and recurrent vomiting episodes. Sepsis screen was negative, blood urea is elevated and urine shows high orotic acid level. Which of the following enzyme is absent?
- A. 1
- B. 2
- C. 3 (Correct Answer)
- D. 4
Explanation: ***Correct Option 3 (Ornithine Transcarbamylase)*** - The presence of **elevated urine orotic acid** is pathognomonic for **ornithine transcarbamylase (OTC) deficiency**. - This occurs because carbamoyl phosphate accumulates in mitochondria when it cannot be converted to citrulline, then leaks into the cytoplasm where it enters the **pyrimidine synthesis pathway**, producing orotic acid. - The elevated blood urea indicates hyperammonemia, and the clinical picture of failure to thrive with recurrent vomiting is classic for OTC deficiency. - **OTC deficiency is the only urea cycle disorder that causes orotic aciduria** because the block occurs after carbamoyl phosphate formation but before citrulline synthesis. *Incorrect Option 1 (N-acetylglutamate synthase)* - N-acetylglutamate synthase produces N-acetylglutamate, which is an **allosteric activator of carbamoyl phosphate synthetase I (CPS1)**. - Deficiency here would impair CPS1 activity, leading to **decreased carbamoyl phosphate formation**. - This would cause hyperammonemia but **not orotic aciduria**, as insufficient carbamoyl phosphate would be available to shunt into pyrimidine synthesis. *Incorrect Option 2 (Carbamoyl Phosphate Synthetase I)* - CPS1 deficiency prevents formation of carbamoyl phosphate from ammonia and CO₂. - This causes severe hyperammonemia with very low or absent carbamoyl phosphate levels. - **No orotic aciduria occurs** because the substrate (carbamoyl phosphate) needed for pyrimidine synthesis is not produced. *Incorrect Option 4 (Downstream urea cycle enzymes)* - Later enzymes in the cycle include argininosuccinate synthetase and argininosuccinate lyase. - Deficiencies cause accumulation of citrulline or argininosuccinate respectively, with hyperammonemia. - **No orotic aciduria occurs** because carbamoyl phosphate is successfully converted to citrulline and doesn't accumulate to shunt into pyrimidine synthesis.
Question 10: Which of the following reactions is responsible for folate trap?
- A. 1
- B. 2 (Correct Answer)
- C. 3
- D. All of the above
Explanation: ***Option 2*** - Reaction 2, catalyzed by **methionine synthase**, is directly responsible for the **folate trap**. - This enzyme uses **5-methyl-THF** (methyl-tetrahydrofolate) as a methyl donor to convert homocysteine to methionine, with **vitamin B12** (methylcobalamin) as a coenzyme. - In **vitamin B12 deficiency**, methionine synthase cannot function, preventing 5-methyl-THF from being converted back to THF. - This causes accumulation of folate in the "trapped" 5-methyl-THF form, which cannot be used for other essential reactions requiring THF (such as DNA synthesis). *Option 1* - Reaction 1 and Reaction 2 are likely **parts of the same methionine synthase reaction**, not separate reactions. - The complete reaction involves: 5-methyl-THF donates its methyl group → vitamin B12 (forming methylcobalamin) → methyl group transfers to homocysteine → forming methionine and regenerating THF. - While this step is part of the overall mechanism, the key point is that **impairment of this cycle due to B12 deficiency** causes the trap, which is most accurately attributed to the methionine synthase reaction as a whole (Reaction 2). *Option 3* - Reaction 3 represents downstream metabolism of methionine, such as formation of **S-adenosylmethionine (SAM)** or transsulfuration pathways. - These reactions are not directly involved in the interconversion of folate forms or the mechanism of the folate trap. *All of the above* - The folate trap specifically refers to the inability to regenerate THF from 5-methyl-THF due to impaired **methionine synthase activity** (Reaction 2) in **vitamin B12 deficiency**. - Only Reaction 2 is directly responsible for this phenomenon.
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