Nucleic Acid Biochemistry Practice Questions

Q: Hyperuricemia is caused in a newborn due to a defect in which of the following enzymes?

Hypoxanthine guanine phosphoribosyltransferase. ### Explanation **Correct Option: D. Hypoxanthine guanine phosphoribosyltransferase (HGPRT)** The question refers to **Lesch-Nyhan Syndrome**, an X-linked recessive disorder caused by a complete deficiency of the enzyme **HGPRT**. This enzyme is crucial for the **Purine Salvage Pathway**, where it converts hypoxanthine to IMP and guanine to GMP. * **Mechanism:** When HGPRT is deficient, these purine bases cannot be salvaged and are instead degraded into **Uric Acid**. * **Result:** This leads to severe hyperuricemia, presenting in newborns or infants with orange "sand" in diapers (uric acid crystals), developmental delay, and characteristic self-mutilation. **Analysis of Incorrect Options:** * **A. Adenosine deaminase (ADA):** Deficiency leads to **Severe Combined Immunodeficiency (SCID)** due to the accumulation of dATP, which is toxic to lymphocytes. It does not cause hyperuricemia. * **B. Ornithine transcarbamylase (OTC):** This is an enzyme of the Urea Cycle. Deficiency leads to **Hyperammonemia** and increased orotic aciduria, not hyperuricemia. * **C. Xanthine oxidase:** This enzyme converts hypoxanthine to xanthine and xanthine to uric acid. A deficiency would lead to **Hypouricemia** and xanthinuria, as uric acid cannot be formed. **High-Yield Clinical Pearls for NEET-PG:** * **Lesch-Nyhan Syndrome Triad:** Hyperuricemia (Gout), Intellectual disability, and Self-mutilation (biting lips/fingers). * **PRPP Levels:** In HGPRT deficiency, **PRPP levels increase** (because it isn't used up in salvage), which further stimulates *de novo* purine synthesis, worsening the hyperuricemia. * **Treatment:** Allopurinol (inhibits xanthine oxidase) is used to manage uric acid levels but does not reverse neurological symptoms.

Q: Which of the following is true regarding Z DNA?

It is formed by an alternating GC sequence.. **Explanation:** Z-DNA is a unique, left-handed double helical structure of DNA that differs significantly from the standard right-handed B-DNA. **Why Option B is Correct:** Z-DNA is favored by sequences containing **alternating purines and pyrimidines**, most notably **alternating GC sequences** (e.g., 5'-GCGCGC-3'). In this configuration, the guanine base undergoes a conformational change from the standard *anti* to the *syn* position, while cytosine remains in the *anti* position. This alternating "zigzag" pattern of the sugar-phosphate backbone gives Z-DNA its name. **Analysis of Incorrect Options:** * **Option A:** Z-DNA is more elongated and thinner than B-DNA. It has **12 base pairs per turn**, which is *more* than the 10.5 base pairs per turn found in B-DNA. * **Option C:** Z-DNA is typically found at the **5' end of genes**, specifically in promoter regions near transcription start sites. It is thought to play a role in regulating gene expression by relieving torsional strain (supercoiling) during transcription. * **Option D:** Methylation of cytosine (specifically at the C5 position) actually **promotes and stabilizes** the formation of Z-DNA rather than inhibiting it. **High-Yield Facts for NEET-PG:** * **Helix Direction:** Z-DNA is the only **left-handed** helix (B and A are right-handed). * **Glycosidic Bond:** Alternating *syn* (for purines) and *anti* (for pyrimidines) conformations. * **Biological Role:** Transiently formed during transcription; associated with areas of active gene expression and DNA supercoiling. * **Comparison Table:** * **B-DNA:** Right-handed, 10.5 bp/turn, *anti* glycosidic bond. * **Z-DNA:** Left-handed, 12 bp/turn, *syn/anti* glycosidic bond.

Q: Which product is excreted unchanged during pyrimidine catabolism?

Pseudouridine. **Explanation:** **Why Pseudouridine is the Correct Answer:** Pseudouridine is a unique C-glycoside isomer of uridine found primarily in **transfer RNA (tRNA)** and ribosomal RNA. Unlike standard nucleosides where the base is linked to ribose via a C-N bond, pseudouridine contains a **C-C bond**. The human body lacks the specific enzymes required to hydrolyze or cleave this stable C-C bond. Consequently, when tRNA is degraded, pseudouridine cannot be catabolized further and is **excreted unchanged in the urine**. It serves as a useful clinical marker for the rate of tRNA turnover. **Analysis of Incorrect Options:** * **A. Uric Acid:** This is the final end product of **purine** (Adenine and Guanine) catabolism in humans. Pyrimidine catabolism does not produce uric acid. * **B. Ammonia:** While ammonia is produced during the deamination steps of pyrimidine catabolism, it is not excreted "unchanged." It is typically converted into **urea** via the urea cycle before excretion. * **D. Beta-alanine:** This is a metabolic end product of **Cytosine and Uracil** degradation. However, it is not excreted "unchanged"; it can be further metabolized to acetyl-CoA or excreted as CO2 and water. **High-Yield NEET-PG Pearls:** * **End products of Pyrimidines:** Cytosine/Uracil → **β-alanine**; Thymine → **β-aminoisobutyrate**. * **Solubility:** Unlike purine end products (uric acid), pyrimidine catabolites are highly **water-soluble**. * **Clinical Marker:** Elevated urinary pseudouridine levels are often seen in conditions with high cell turnover, such as **malignancies** or leukemia.

Q: If one strand of isolated DNA showed 20% Adenine (A), 25% Guanine (G), 30% Cytosine (C), and 22% Thymine (T), how many A, G, C, and T bases would be expected in both strands together?

A=42%, G=55%, C=55%, T=42%. ### Explanation **Underlying Concept: Chargaff’s Rule and Complementary Base Pairing** In double-stranded DNA (dsDNA), the total amount of purines equals the total amount of pyrimidines. According to **Chargaff’s Rule**, Adenine (A) always pairs with Thymine (T), and Guanine (G) always pairs with Cytosine (C). Therefore, the percentage of a base in the total dsDNA is the average of its percentage on the two individual strands. **Step-by-Step Calculation:** 1. **Strand 1 (Given):** A=20%, G=25%, C=30%, T=22% (Note: These don't sum to 100% in the question stem, but the calculation follows the logic of complementarity). 2. **Strand 2 (Complementary):** Because A pairs with T and G pairs with C: * A in Strand 2 = T in Strand 1 = 22% * T in Strand 2 = A in Strand 1 = 20% * G in Strand 2 = C in Strand 1 = 30% * C in Strand 2 = G in Strand 1 = 25% 3. **Total (Both Strands):** * **A:** (20 + 22) = **42%** * **T:** (22 + 20) = **42%** * **G:** (25 + 30) = **55%** * **C:** (30 + 25) = **55%** **Why Incorrect Options are Wrong:** * **Options A, B, and C:** These options violate Chargaff’s Rule for double-stranded DNA. In dsDNA, the amount of **A must equal T** and **G must equal C**. In these options, the ratios are asymmetrical (e.g., in Option B, A=50% but T=47%), which is only possible in single-stranded DNA (ssDNA) or RNA. **High-Yield Clinical Pearls for NEET-PG:** * **Chargaff’s Rule** applies only to **double-stranded DNA**. It does not apply to single-stranded DNA (like the φX174 virus) or RNA. * **Melting Temperature (Tm):** DNA with higher G-C content has a higher Tm because G-C pairs have **three hydrogen bonds**, whereas A-T pairs have only two. * **Clinical Correlation:** Certain chemotherapy drugs (like Dactinomycin) intercalate specifically into G-C rich regions of DNA to inhibit transcription.

Q: What is the total number of ATP molecules required for de novo purine synthesis?

5. **Explanation:** The synthesis of the first purine nucleotide, **Inosine Monophosphate (IMP)**, is an energy-intensive process occurring in the cytosol. To reach the final product (IMP) from the starting material (Ribose-5-Phosphate), a total of **5 ATP molecules** are consumed. 1. **Step 1:** Ribose-5-Phosphate to PRPP (1 ATP → AMP; equivalent to **2 high-energy phosphate bonds**). 2. **Step 5:** Formation of Glycinamide ribonucleotide (GAR) (**1 ATP**). 3. **Step 7:** Formation of Formylglycinamidine ribonucleotide (FGAM) (**1 ATP**). 4. **Step 8:** Closure of the imidazole ring to form AIR (**1 ATP**). 5. **Step 10:** Formation of Succinylaminoimidazole carboxamide ribonucleotide (SAICAR) (**1 ATP**). While 6 high-energy phosphate bonds are broken, the question refers to the number of distinct enzymatic steps requiring ATP, which is 5. **Analysis of Incorrect Options:** * **Option A (2):** This significantly underestimates the complexity of the 11-step pathway. * **Option C (6):** This is a common point of confusion. While 6 high-energy phosphate bonds are consumed (because the first step produces AMP), the number of ATP molecules utilized as substrates is 5. * **Option D (4):** This does not account for all the phosphorylation and ring-closure steps required for the purine skeleton. **High-Yield Clinical Pearls for NEET-PG:** * **Rate-limiting step:** Glutamine-PRPP amidotransferase (Step 2). * **Key Donors:** Glycine (entire molecule), Aspartate (Nitrogen), Glutamine (Nitrogen), and **Tetrahydrofolate (THF)** (Carbon atoms C2 and C8). * **Clinical Correlation:** Methotrexate and Sulfonamides inhibit purine synthesis by interfering with folate metabolism, making them effective as anti-cancer and anti-microbial agents respectively.

Q: Which of the following does not contribute to the pyrimidine ring synthesis?

Tetrahydrofolate (THF). ### Explanation The synthesis of the pyrimidine ring is a de novo process that constructs a six-membered heterocyclic ring. Unlike purine synthesis, which is built upon a ribose-5-phosphate foundation, the pyrimidine ring is synthesized first and then attached to the ribose unit. **Why Tetrahydrofolate (THF) is the Correct Answer:** Tetrahydrofolate (THF) derivatives (specifically N10-formyl THF) are essential donors of carbon atoms in **purine** synthesis (C2 and C8). In **pyrimidine** synthesis, THF is **not** involved in the formation of the ring itself. Its only role in pyrimidine metabolism occurs *after* the ring is formed, during the conversion of dUMP to dTMP by thymidylate synthase, where N5,N10-methylene THF acts as a methyl donor. **Analysis of Incorrect Options:** * **Aspartate (A):** Provides the majority of the pyrimidine ring, contributing three carbons (C4, C5, C6) and one nitrogen (N1). * **Glutamine (B):** The amide group of glutamine provides the nitrogen at the N3 position. This reaction is catalyzed by **Carbamoyl Phosphate Synthetase II (CPS-II)**, the rate-limiting enzyme of the pathway. * **Bicarbonate (D):** Provides the carbon atom at the C2 position of the ring. **High-Yield Clinical Pearls for NEET-PG:** * **Rate-limiting enzyme:** CPS-II (located in the cytosol), inhibited by UTP and activated by PRPP. * **Leflunomide:** An immunosuppressant used in Rheumatoid Arthritis that inhibits **Dihydroorotate dehydrogenase**, blocking de novo pyrimidine synthesis. * **Orotic Aciduria:** Caused by a deficiency of UMP Synthase. It presents with megaloblastic anemia (refractory to B12/Folate) and growth retardation. Treatment is oral **Uridine** supplementation. * **Mnemonic for Pyrimidine atoms:** **"CAD"** — **C**arbamoyl phosphate (from Glutamine + CO2) and **As**partate.

Q: What protein forms the core of a nucleosome?

Histones. **Explanation:** The **nucleosome** is the fundamental repeating unit of eukaryotic chromatin, often described as "beads on a string." **1. Why Histones are correct:** The core of a nucleosome consists of an **octamer of histone proteins**. This octamer contains two copies each of four highly conserved histones: **H2A, H2B, H3, and H4**. Approximately 146 base pairs of DNA wrap around this protein core 1.75 times. Histones are rich in basic amino acids like **Lysine and Arginine**, giving them a positive charge. This allows them to bind tightly to the negatively charged phosphate backbone of DNA. **2. Why other options are incorrect:** * **DNA:** DNA is the genetic material that wraps *around* the core; it does not form the core itself. * **RNA:** RNA is involved in transcription and translation (mRNA, tRNA, rRNA) but is not a structural component of the nucleosome core. **3. NEET-PG High-Yield Facts:** * **Linker Histone:** **H1** is known as the "linker histone." It binds to the DNA between nucleosome beads and helps stabilize the 30-nm chromatin fiber. It is **not** part of the octamer core. * **Charge Interaction:** The interaction between histones and DNA is ionic, not covalent. * **Acetylation:** Histone acetylation (by HATs) neutralizes the positive charge on lysine, weakening the DNA-histone bond and leading to **euchromatin** (transcriptionally active). * **Deacetylation:** Histone deacetylation (by HDACs) restores the positive charge, leading to **heterochromatin** (transcriptionally silent).

Q: What is the rate-limiting enzyme of purine nucleotide synthesis?

PRPP glutamyl amido-transferase. **Explanation:** The synthesis of purine nucleotides occurs via the **De Novo pathway**, where the purine ring is built upon a ribose-5-phosphate foundation. **1. Why PRPP glutamyl amido-transferase is correct:** The committed and rate-limiting step of purine synthesis is the conversion of **5-Phosphoribosyl-1-pyrophosphate (PRPP)** to **5-Phosphoribosylamine**. This reaction is catalyzed by **PRPP glutamyl amido-transferase**. * **Mechanism:** It involves the displacement of the pyrophosphate group from PRPP by an amide group from Glutamine. * **Regulation:** This enzyme is strictly regulated via feedback inhibition by the end products: AMP, GMP, and IMP. High levels of PRPP act as a feed-forward activator. **2. Why other options are incorrect:** * **Xanthine oxidase:** This is an enzyme involved in the **catabolism** (breakdown) of purines, converting hypoxanthine to xanthine and xanthine to uric acid. It is the target of Allopurinol. * **HGPRT:** This is the key enzyme of the **Purine Salvage Pathway**, not de novo synthesis. Its deficiency leads to **Lesch-Nyhan Syndrome**. * **Adenosine deaminase (ADA):** This enzyme is involved in purine degradation (converting adenosine to inosine). Its deficiency leads to **Severe Combined Immunodeficiency (SCID)**. **Clinical Pearls for NEET-PG:** * **Source of Atoms:** Remember the contributors to the purine ring: **CO₂** (C6), **Glycine** (C4, C5, N7), **Aspartate** (N1), **Glutamine** (N3, N9), and **Formyl-THF** (C2, C8). * **Rate-limiting step of Pyrimidine synthesis:** Carbamoyl phosphate synthetase II (CPS-II). * **Inhibitor:** The drug **Azathioprine** (immunosuppressant) is converted to 6-mercaptopurine, which inhibits PRPP glutamyl amido-transferase.

Question 1

Hyperuricemia is caused in a newborn due to a defect in which of the following enzymes?

Accepted Answer

Hypoxanthine guanine phosphoribosyltransferase

Answer

Adenosine deaminase

Answer

Ornithine transcarbamylase

Answer

Xanthine oxidase

Question 2

Which of the following is true regarding Z DNA?

Accepted Answer

It is formed by an alternating GC sequence.

Answer

It has fewer base pairs per turn than B DNA.

Answer

It tends to be found at the 3' end to genes.

Answer

It is inhibited by methylation of the bases.

Question 3

Which product is excreted unchanged during pyrimidine catabolism?

Accepted Answer

Pseudouridine

Answer

Uric acid

Answer

Ammonia

Answer

Beta alanine

Question 4

If one strand of isolated DNA showed 20% Adenine (A), 25% Guanine (G), 30% Cytosine (C), and 22% Thymine (T), how many A, G, C, and T bases would be expected in both strands together?

Accepted Answer

A=42%, G=55%, C=55%, T=42%

Answer

A=45%, G=45%, C=52%, T=52%

Answer

A=50%, G=47%, C=50%, T=47%

Answer

A=44%, G=55%, C=55%, T=44%

Question 5

What is the total number of ATP molecules required for de novo purine synthesis?

Accepted Answer

5

Answer

2

Answer

6

Answer

4

Question 6

Which of the following does not contribute to the pyrimidine ring synthesis?

Accepted Answer

Tetrahydrofolate (THF)

Answer

Aspartate

Answer

Glutamine

Answer

Bicarbonate

Question 7

What protein forms the core of a nucleosome?

Accepted Answer

Histones

Answer

DNA

Answer

RNA

Answer

None of the above

Question 8

What is the rate-limiting enzyme of purine nucleotide synthesis?

Accepted Answer

PRPP glutamyl amido-transferase

Answer

Xanthine oxidase

Answer

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)

Answer

Adenosine deaminase (ADA)

Question 9

Base stacking of DNA is characterized by?

Accepted Answer

Hyperchromicity

Answer

Electrophoresis

Answer

Linear dichromicity

Answer

Hypochromicity

Question 10

What is true about a nucleosome?

Accepted Answer

It is a regular repeating structure of DNA and histone proteins.

Answer

It uses only one type of histone protein.

Answer

Each complex is separated from the next by non-histone proteins.

Answer

It reflects a small nucleus.

Nucleic Acid Biochemistry — MCQs

Nucleic Acid Biochemistry — MCQs

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