NEET-PG 2025 — Biochemistry
9 Previous Year Questions with Answers & Explanations
A child presents with a history of fractures, multiple petechiae, perifollicular hemorrhages, and gum bleeding. Which of the following enzyme defects is involved?
A patient has elevated phenylalanine levels (40 mg/dL), but phenylalanine hydroxylase enzyme levels are normal. Which cofactor deficiency is most likely responsible for this condition?
A man is trapped in a tunnel for 5 consecutive days without access to food but survives. What is the primary source of energy for his brain during this period?
A patient presents with anemia, positive Romberg sign, and other neurological findings suggestive of vitamin B12 deficiency. Laboratory findings show elevated homocysteine levels. Which amino acid is likely to be deficient in this patient?
A neonate presents with seizures and is found to have a cherry red spot on fundus examination. Enzyme assay reveals deficiency of hexosaminidase A. Which of the following substances is most likely to be accumulated in this patient?
A frameshift mutation occurs due to the insertion of a new nucleotide at the 4th position of an mRNA sequence with 900 nucleotides. What is the most likely outcome of this mutation?
A patient presents with skin cancer and hyperpigmentation that worsens with sunlight exposure. Which of the following DNA repair mechanisms is most likely defective in this condition?
Which of the following is a mitochondrial inheritance disorder?
A child presents with developmental delay and coarse facial features. Enzyme assay reveals a deficiency of α-L-iduronidase. Which of the following substances is most likely to accumulate in this condition?
NEET-PG 2025 - Biochemistry NEET-PG Practice Questions and MCQs
Question 1: A child presents with a history of fractures, multiple petechiae, perifollicular hemorrhages, and gum bleeding. Which of the following enzyme defects is involved?
- A. Tyrosinase
- B. Prolyl hydroxylase (Correct Answer)
- C. Alkaline phosphatase
- D. Lysyl oxidase
Explanation: ***Prolyl hydroxylase*** - **Vitamin C (Ascorbic acid)** is a necessary cofactor for Prolyl hydroxylase and Lysyl hydroxylase, which are essential for the hydroxylation of proline and lysine residues in procollagen. - Deficiency of Vitamin C leads to inactivation of this enzyme, resulting in unstable and defective **collagen** that causes vascular fragility (leading to petechiae and gum bleeding) and impaired bone matrix (resulting in fractures). *Lysyl oxidase* - **Lysyl oxidase** is required for the crucial cross-linking of collagen and elastin fibers, a process that relies on **copper**, not Vitamin C, as a main cofactor. - A defect in this enzyme primarily causes syndromes like certain types of **Ehlers-Danlos Syndrome** (Type V) or features associated with **Menkes disease**. *Tyrosinase* - **Tyrosinase** is the key enzyme in the biosynthesis of **melanin** from tyrosine. - A defect in Tyrosinase causes various forms of **Albinism**, characterized by lack of pigmentation in the skin, hair, and eyes, which is unrelated to the described hemorrhagic and skeletal findings. *Alkaline phosphatase* - **Alkaline phosphatase (ALP)** plays a vital role in bone mineralization by hydrolyzing pyrophosphate, preventing its inhibitory effect on calcification. - While important for bone health, ALP deficiency causes **Hypophosphatasia**, and it is not directly involved in the pathogenesis of structural collagen defects seen in **Scurvy**.
Question 2: A patient has elevated phenylalanine levels (40 mg/dL), but phenylalanine hydroxylase enzyme levels are normal. Which cofactor deficiency is most likely responsible for this condition?
- A. Tetrahydrofolate
- B. Tetrahydrobiopterin (BH4) (Correct Answer)
- C. Pyridoxine
- D. Thiamine
Explanation: ***Tetrahydrobiopterin (BH4)*** - The conversion of **phenylalanine to tyrosine** by phenylalanine hydroxylase (PAH) absolutely requires the cofactor **Tetrahydrobiopterin (BH4)**. - Normal PAH enzyme levels combined with high phenylalanine (hyperphenylalaninemia) strongly indicates a defect in the essential cofactor (BH4 deficiency), often leading to a potentially treatable condition known as **Malignant PKU**. *Tetrahydrofolate* - **Tetrahydrofolate (THF)** is primarily involved in **one-carbon metabolism** and the transfer of methyl groups, crucial for purine and pyrimidine synthesis. - Its deficiency typically leads to **megaloblastic anemia** and neurological symptoms but does not directly impair phenylalanine hydroxylase activity. *Thiamine* - The active form, **Thiamine Pyrophosphate (TPP)**, is an essential cofactor for **dehydrogenase enzymes**, such as pyruvate dehydrogenase and $\alpha$-ketoglutarate dehydrogenase. - Deficiency is classically associated with impaired carbohydrate metabolism and results in conditions like **Beriberi**. *Pyridoxine* - **Pyridoxal phosphate (PLP)**, derived from pyridoxine, is a cofactor for manifold reactions in amino acid metabolism, including **transaminases** and decarboxylases. - While vital for general amino acid handling, it is not the required cofactor for the specific hydroxylation reaction catalyzed by **phenylalanine hydroxylase**.
Question 3: A man is trapped in a tunnel for 5 consecutive days without access to food but survives. What is the primary source of energy for his brain during this period?
- A. Ketone bodies (Correct Answer)
- B. Glycogenolysis
- C. Lipolysis
- D. Gluconeogenesis
Explanation: ***Ketone bodies*** - During prolonged fasting (beyond 48-72 hours, such as 5 days), the liver generates **ketone bodies** (β-hydroxybutyrate and acetoacetate) from fatty acid oxidation via **ketogenesis**. - These **ketone bodies** efficiently cross the **blood-brain barrier** and replace up to **60-70%** of the brain's energy needs during prolonged starvation, thus conserving essential muscle protein. - This metabolic adaptation (ketosis) is crucial for survival during extended fasting periods. *Gluconeogenesis* - **Gluconeogenesis** (synthesis of new glucose from non-carbohydrate precursors) remains active during starvation to provide glucose for obligate glucose users like **RBCs** and the renal medulla. - However, the brain minimizes its dependence on glucose and shifts primarily to ketone body utilization by day 5. - Primary substrates for gluconeogenesis are **amino acids** (from muscle protein) and **glycerol** (from lipolysis). *Glycogenolysis* - **Glycogenolysis** (breakdown of liver glycogen to glucose) is the first-line response during early fasting, typically lasting only **12-24 hours**. - By 5 consecutive days, liver glycogen stores are **completely depleted**, making this pathway inactive and unable to fuel the brain. *Lipolysis* - **Lipolysis** (breakdown of adipose triglycerides) releases **fatty acids** and **glycerol** into circulation. - Fatty acids fuel peripheral tissues (skeletal muscle, heart) but **cannot cross the blood-brain barrier** efficiently. - Lipolysis provides substrates for hepatic ketogenesis, but is not the direct energy source for the brain itself.
Question 4: A patient presents with anemia, positive Romberg sign, and other neurological findings suggestive of vitamin B12 deficiency. Laboratory findings show elevated homocysteine levels. Which amino acid is likely to be deficient in this patient?
- A. Methionine (Correct Answer)
- B. Tyrosine
- C. Cysteine
- D. Glutamate
Explanation: ***Methionine*** - Vitamin B12 is an essential cofactor for the enzyme **methionine synthase**, which converts **homocysteine** into methionine. - A deficiency in B12 blocks this essential metabolic step, leading to the accumulation of homocysteine and a resultant deficiency of **methionine**. *Cysteine* - **Cysteine** is derived from methionine via **homocysteine** and requires **Vitamin B6** (pyridoxal phosphate) for its synthesis, not Vitamin B12 directly. - While B12 deficiency results in increased homocysteine which is an intermediate, the direct deficiency relates to the product of the B12-dependent step, **methionine**. *Tyrosine* - **Tyrosine** is synthesized from **phenylalanine** by the enzyme phenylalanine hydroxylase, a pathway entirely separate from **Vitamin B12** and homocysteine metabolism. - It is generally considered a non-essential amino acid whose metabolism is disturbed primarily in conditions like **Phenylketonuria (PKU)**. *Glutamate* - **Glutamate** is a crucial excitatory neurotransmitter whose synthesis and metabolism are not directly linked to the **methionine synthase** reaction or **Vitamin B12** deficiency. - Neurological symptoms associated with B12 deficiency (like Romberg sign) are due to impaired **myelin synthesis** caused by reduced SAM (derived from methionine) and methylmalonyl-CoA accumulation.
Question 5: A neonate presents with seizures and is found to have a cherry red spot on fundus examination. Enzyme assay reveals deficiency of hexosaminidase A. Which of the following substances is most likely to be accumulated in this patient?
- A. GM1 ganglioside
- B. Sphingomyelin
- C. GM2 ganglioside (Correct Answer)
- D. Glucocerebroside
Explanation: ***GM2 ganglioside*** - Deficiency of **Hexosaminidase A** results in the accumulation of **GM2 ganglioside**, defining features of **Tay-Sachs disease**. - The accumulation of GM2 ganglioside in the retina's ganglion cells causes the characteristic **cherry red spot** on fundus examination. *GM1 ganglioside* - The accumulation of **GM1 ganglioside** occurs in **GM1 gangliosidosis**, due to a deficiency of **β-galactosidase**. - GM1 gangliosidosis typically presents with coarse facial features, hepatosplenomegaly, and skeletal deformities (**dysostosis multiplex**), features not always prominent in Tay-Sachs. *Sphingomyelin* - Accumulation of **Sphingomyelin** is the diagnostic feature of **Niemann-Pick disease** (especially Type A), caused by a deficiency of **sphingomyelinase**. - While Niemann-Pick Type A also causes a cherry red spot, it is classically associated with rapid neurodegeneration and marked **hepatosplenomegaly** and **foam cells** (lipid-laden macrophages). *Glucocerebroside* - This lipid accumulates in **Gaucher disease** because of deficient **glucocerebrosidase** activity. - Gaucher disease is characterized by bony involvement, pancytopenia, and massive **hepatosplenomegaly**, and does not typically feature the cherry red spot.
Question 6: A frameshift mutation occurs due to the insertion of a new nucleotide at the 4th position of an mRNA sequence with 900 nucleotides. What is the most likely outcome of this mutation?
- A. Partial protein production (Correct Answer)
- B. Complete change in protein production
- C. No protein production
- D. No change in the final protein
Explanation: ***Partial protein production*** - The insertion of a single nucleotide at position 4 causes a **frameshift mutation**, which fundamentally alters the reading frame starting from the second codon. - Frameshift mutations typically lead to the introduction of a **Premature Termination Codon (PTC)** shortly downstream, resulting in the synthesis of a **truncated** (partial) and non-functional protein. *No change in the final protein* - A change from position 4 onward affects almost the entire coding sequence; thus, there cannot be **no change** in the protein structure. - Only an insertion/deletion of a multiple of three nucleotides (in-frame mutation) or a mutation late in the sequence might result in a preserved protein function. *Complete change in protein production* - While the subsequent mRNA sequence is entirely changed, the outcome on the protein level is usually **truncation** (partial protein), not the complete synthesis of a full-length, completely altered protein. - The term "complete change" is less accurate than "partial production," as the protein synthesis is typically **aborted prematurely**. *No protein production* - The **start codon** (positions 1-3) is upstream of the mutation site (position 4) and remains intact, allowing for **translation initiation** to occur normally. - Protein production starts; it is only terminated prematurely when a stop codon is encountered in the shifted reading frame.
Question 7: A patient presents with skin cancer and hyperpigmentation that worsens with sunlight exposure. Which of the following DNA repair mechanisms is most likely defective in this condition?
- A. Base excision repair
- B. Mismatch repair
- C. Nucleotide excision repair (Correct Answer)
- D. Non-homologous end joining (NHEJ)
Explanation: ***Nucleotide excision repair*** - This mechanism is responsible for repairing large, bulky DNA lesions, most notably **pyrimidine dimers** caused by **UV radiation** (sunlight). - A defect in NER is the underlying cause of **Xeroderma Pigmentosum**, which presents with severe photosensitivity, hyperpigmentation, and a significantly increased risk of **skin cancer** (melanoma and non-melanoma). *Base excision repair* - Primarily repairs **small, non-helix-distorting lesions** caused by spontaneous factors (like deamination) or oxidative damage, such as single base modifications. - Defective BER is implicated in hereditary cancers like MUTYH-associated polyposis (MAP), which is not associated with **UV-induced skin pathology**. *Non-homologous end joining (NHEJ)* - Responsible for repairing **double-strand breaks (DSBs)** in DNA, usually in the G0/G1 phase of the cell cycle. - While critical for genome stability, defects in NHEJ lead to severe immunodeficiency (due to impaired V(D)J recombination) and are not the primary cause of susceptibility to **solar-induced skin cancer**. *Mismatch repair* - Corrects errors (mismatched bases) incorporated during **DNA replication** that escape proofreading. - Defective MMR leads to a high frequency of microsatellite instability, characteristic of conditions like **Hereditary Non-polyposis Colorectal Cancer (HNPCC)** or Lynch syndrome, but not the primary cause of photosensitivity and UV-related skin cancer.
Question 8: Which of the following is a mitochondrial inheritance disorder?
- A. Achondroplasia
- B. Cystic fibrosis
- C. Williams syndrome
- D. Kearns-Sayre syndrome (Correct Answer)
Explanation: ***Kearns-Sayre syndrome*** - It is a classic example of a **mitochondrial encephalomyopathy** resulting from large-scale deletions or duplications of mitochondrial DNA (**mtDNA**). - It is characterized clinically by the triad of **chronic progressive external ophthalmoplegia (CPEO)**, **retinitis pigmentosa**, and onset before age 20. - Follows **maternal inheritance** pattern typical of mitochondrial disorders. *Williams syndrome* - Williams syndrome is a disorder caused by a **microdeletion** of several genes on chromosome 7 (7q11.23). - It is inherited in an **autosomal dominant** fashion, though most cases arise spontaneously. *Achondroplasia* - This is the most common form of genetic dwarfism caused by a mutation in the **FGFR3 gene** (Fibroblast Growth Factor Receptor 3). - It exhibits an **autosomal dominant** inheritance pattern. *Cystic fibrosis* - Cystic fibrosis is caused by mutations in the **CFTR gene** (Cystic Fibrosis Transmembrane conductance Regulator) on chromosome 7. - It is transmitted via an **autosomal recessive** inheritance pattern.
Question 9: A child presents with developmental delay and coarse facial features. Enzyme assay reveals a deficiency of α-L-iduronidase. Which of the following substances is most likely to accumulate in this condition?
- A. Only Dermatan sulfate
- B. Heparan sulfate + Chondroitin sulfate
- C. Dermatan sulfate + Chondroitin sulfate
- D. Dermatan sulfate + Heparan sulfate (Correct Answer)
Explanation: ***Dermatan sulfate + Heparan sulfate*** - The presenting features of developmental delay and **coarse facial features** point towards a Mucopolysaccharidosis (MPS). - A deficiency of **α-L-iduronidase** is diagnostic of **MPS Type I (Hurler syndrome)**, which leads to the accumulation of **Dermatan sulfate** and **Heparan sulfate**. *Dermatan sulfate + Chondroitin sulfate* - While **Dermatan sulfate** accumulates in MPS I, **Chondroitin sulfate** accumulation is characteristic of **MPS IV (Morquio syndrome)**, which has different clinical features (skeletal dysplasia, normal intelligence). - This combination does not correctly represent the primary storage products of **MPS I**. *Only Dermatan sulfate* - Both **MPS I (Hurler syndrome)** and **MPS II (Hunter syndrome)** result in accumulation of **both Dermatan sulfate AND Heparan sulfate**, not dermatan sulfate alone. - Listing dermatan sulfate alone is incomplete and does not accurately reflect the biochemical defect in **α-L-iduronidase deficiency**. *Heparan sulfate + Chondroitin sulfate* - **Heparan sulfate** does accumulate in MPS I, but the co-accumulation is with **Dermatan sulfate**, not Chondroitin sulfate. - **Chondroitin sulfate** accumulation is characteristic of **MPS IV (Morquio syndrome)**, which involves different enzyme deficiencies.