FMGE 2025 - Biochemistry Practice Questions

Q: Which of the following amino acids primarily acts as a buffer in blood due to its ability to accept and donate protons at physiological pH?

Histidine. ***Histidine***- The side chain of **histidine**, the **imidazole group**, has a pKa of approximately 6.0, which is close to the physiological pH of **7.4**, making it an effective buffer.- This property is especially vital for the **buffering capacity of hemoglobin** in red blood cells, contributing significantly to pH homeostasis (Bohr effect).*Arginine*- Arginine possesses a **guanidinium group** in its side chain with a very high pKa (~12.5).- This high pKa means its side chain is almost always positively charged and protonated at physiological pH, rendering it ineffective as a physiological **acid-base buffer**.*Tryptophan*- Tryptophan has a large, non-polar **indole ring** side chain, which is chemically inert and lacks an ionizable group within the physiological pH range.- Since it cannot accept or donate protons near pH 7.4, it does not contribute to the **buffering system** of the blood.*Tyrosine*- Tyrosine contains a **phenolic hydroxyl group** with a pKa of approximately 10.5.- Because its pKa is significantly higher than physiological pH, it is largely neutral and incapable of mediating proton exchange effectively in the **blood plasma**.

Q: During starvation, which of the following hormones is primarily produced to maintain blood glucose levels?

Glucagon. ***Glucagon*** - Glucagon is the **primary counter-regulatory hormone** secreted by the pancreatic **alpha cells** in response to hypoglycemia during starvation. - It acts mainly on the liver to stimulate rapid glucose release through **glycogenolysis** and sustain long-term glucose production via **gluconeogenesis**. - Glucagon levels rise significantly within hours of fasting and remain elevated throughout prolonged starvation. *Insulin* - Insulin is an **anabolic hormone** secreted in response to high blood glucose (hyperglycemia) to promote storage and glucose uptake, thus lowering blood glucose levels. - During starvation, insulin secretion is characteristically **suppressed** to minimize glucose uptake by peripheral tissues and conserve it for the brain. *Cortisol* - Cortisol is a **glucocorticoid stress hormone** that does increase during prolonged starvation and contributes to gluconeogenesis and protein catabolism. - However, **glucagon is the primary and most rapid responder** to falling blood glucose levels, making it the correct answer to this question. *Somatostatin* - Somatostatin is a **paracrine inhibitor** secreted by pancreatic delta cells that locally suppresses the release of both insulin and glucagon. - While it modulates islet function, it is not the primary hormone responsible for mobilizing stored fuels and **raising blood glucose** during periods of fasting.

Q: The development of cataracts in patients with Diabetes Mellitus is primarily due to the accumulation of which of the following substances in the lens?

Sorbitol. ***Correct Option: Sorbitol*** - In the setting of chronic **hyperglycemia**, excess glucose is converted into **sorbitol** by the enzyme **aldose reductase** via the polyol pathway. - Sorbitol is poorly transported out of the lens cells and its accumulation creates an internal **osmotic gradient**, drawing water into the lens, which leads to cell swelling, lens fiber disruption, and eventual **cataract** formation. - This is the **primary mechanism** of diabetic cataract development. *Incorrect Option: Galactitol* - **Galactitol** (also known as dulcitol) is the specific sugar alcohol that accumulates when there is deficiency of **galactokinase** or **galactose-1-phosphate uridyltransferase**. - Its accumulation is characteristic of **galactosemia**, where high galactose levels lead to its formation via aldose reductase, causing congenital cataracts in that condition, not diabetic cataracts. *Incorrect Option: Fructose* - While **fructose** is produced from sorbitol by sorbitol dehydrogenase in the polyol pathway, it is readily metabolized and does not accumulate in lens tissue. - Fructose itself does not cause osmotic damage or cataract formation in diabetes. *Incorrect Option: Mannitol* - **Mannitol** is a hexahydric sugar alcohol primarily used pharmacologically as an osmotic diuretic for conditions like **cerebral edema**. - It is not an endogenous product of glucose metabolism in the lens and is not associated with diabetic cataract formation.

Q: A patient presents with multiple colonic polyps and has been diagnosed with colorectal carcinoma. There is a strong family history of Hereditary Non-Polyposis Colorectal Cancer (HNPCC). Which DNA repair mechanism is most likely defective in this condition?

Mismatch repair. ***Mismatch repair***- **HNPCC (Lynch syndrome)** is caused by inherited germline mutations in genes (e.g., *MLH1*, *MSH2*) that are responsible for the **mismatch repair (MMR)** pathway. - The failure of MMR leads to the accumulation of errors, specifically in repetitive DNA sequences, resulting in **microsatellite instability** which drives carcinogenesis.*Nucleotide excision repair*- This mechanism repairs bulky helix-distorting lesions in DNA, most commonly **pyrimidine dimers** caused by UV radiation. - A classic disease associated with defective **NER** is **Xeroderma Pigmentosum**, which presents with extreme sun sensitivity and a high risk of skin cancers.*Base excision repair*- This pathway primarily corrects small, non-helix distorting damage, such as oxidized or alkylated bases, utilizing enzymes like **DNA glycosylases**.- While fundamental for DNA maintenance, primary defects in BER are not the underlying cause of pathogenesis in **Lynch syndrome**.*Double-strand break repair*- This mechanism repairs severe damage where the entire DNA helix is broken, typically via **Homologous Recombination (HR)** or **Non-Homologous End Joining (NHEJ)**. - Defects in HR are often linked to hereditary breast and ovarian cancers (e.g., *BRCA1*/ *BRCA2* mutations) and are distinct from the pathogenesis of **HNPCC**.

Q: What is the primary protein that binds to thyroxine?

Thyroxine-binding globulin. ***Thyroxine-binding globulin*** - **TBG** is a single chain glycoprotein that is the primary transporter, binding approximately 70-80% of circulating **T4** (thyroxine) and a smaller proportion of T3. - It serves as a high-affinity reservoir, maintaining hormonal homeostasis and contributing to the long **half-life** of T4. *Follistatin* - **Follistatin** binds and inhibits the activity of **activin** and is primarily involved in regulating the release of **FSH** (follicle-stimulating hormone) from the pituitary. - It has no functional role in the systemic transport or binding of thyroid hormones. *Transthyretin* - **Transthyretin** (or prealbumin) is the second most abundant carrier, binding about 10-15% of circulating T4, and is the principal carrier of **retinol** (Vitamin A). - Although it transports T4, its binding affinity and capacity are significantly lower than those of **TBG**, thus it is not the primary binder. *Transferrin* - **Transferrin** is the main plasma protein responsible for transporting **ferric iron (Fe3+)** throughout the body. - Its binding specificity is strictly for iron and does not involve the transport of **thyroxine**.

Q: Which vitamin deficiency can lead to lactic acidosis?

Thiamine. ***Thiamine*** - **Thiamine (Vitamin B1)** is a crucial cofactor for the enzyme **pyruvate dehydrogenase (PDH)**, which converts **pyruvate** to **acetyl-CoA** to enter the Krebs cycle. - When thiamine is deficient, pyruvate cannot be processed efficiently, leading to its accumulation and subsequent shunting into **lactate** via **lactate dehydrogenase**, thus causing **lactic acidosis**, characteristic of **beriberi**. *Riboflavin* - Riboflavin (Vitamin B2) is a precursor for the coenzymes **FAD** and **FMN**, essential for redox reactions, but its deficiency symptoms mainly involve the oral cavity and skin. - Deficiency leads to **angular cheilitis**, **glossitis**, and **corneal vascularization**, and is not the direct cause of severe lactic acidosis. *Niacin* - Niacin (Vitamin B3) is a precursor for **NAD+** and **NADP+**, vital for many metabolic reactions. - Deficiency causes **pellagra**, characterized by the 3 D's: **Dermatitis**, **Diarrhea**, and **Dementia**, not primarily lactic acidosis. *Biotin* - Biotin (Vitamin B7) acts as a coenzyme for **carboxylase enzymes** (e.g., pyruvate carboxylase, acetyl-CoA carboxylase), which are necessary for gluconeogenesis and fatty acid synthesis. - While **pyruvate carboxylase** uses biotin, thiamine deficiency specifically impairs the key step of converting pyruvate to acetyl-CoA (via PDH complex), making it the primary cause of vitamin-deficiency-related lactic acidosis.

Q: Which of the following enzymes is responsible for the immortality of cancer cells?

Telomerase. ***Telomerase*** **Telomerase** is a **ribonucleoprotein enzyme** that adds repetitive DNA sequences (TTAGGG) to the ends of chromosomes (**telomeres**), counteracting the natural shortening that occurs during cell division. The activation of **telomerase** is characteristic of most cancer cells, granting them the ability to divide indefinitely, fulfilling the hallmark of **unlimited replicative potential** (immortality). *Topoisomerase* This enzyme is crucial for relieving the **torsional strain** (supercoiling) in the DNA helix that arises ahead of the replication fork or during transcription. Its primary role is managing DNA structure and integrity, not determining cellular lifespan or **immortality** through **telomere** maintenance. *Helicase* **Helicases** are motor proteins that use energy from ATP hydrolysis to **unwind nucleic acid duplexes** (like the DNA double helix) in fundamental processes such as DNA replication, repair, and transcription. While essential for replication, it does not prevent the gradual loss of terminal DNA sequences (**telomeres**) required for cancer cell immortality. *RNA polymerase* This enzyme is responsible for **transcription**, the process of synthesizing an **RNA molecule** from a DNA template. Its function is focused on gene expression (protein synthesis) and is not directly involved in maintaining the length of **telomeres** or conferring replicative immortality upon cells.

Q: Which of the following acts as a major intracellular antioxidant and helps in detoxifying reactive oxygen species?

Glutathione. ***Glutathione (Correct Answer)*** - **It is the most abundant non-enzymatic intracellular antioxidant**, found in high concentrations in nearly all cells. - It detoxifies **reactive oxygen species (ROS)**, particularly **hydrogen peroxide** and lipid hydroperoxides, through the **glutathione redox cycle**. - As a **tripeptide molecule** (not an enzyme), it directly acts as the major intracellular antioxidant. *Catalase (Incorrect)* - This is an **enzyme** responsible for the rapid decomposition of two molecules of **hydrogen peroxide (H₂O₂)** into water and oxygen. - While crucial for detoxification in peroxisomes, it is an enzyme, not the primary non-enzymatic antioxidant molecule like glutathione. *Superoxide dismutase (Incorrect)* - This is a **metalloenzyme** that catalyzes the dismutation of the highly reactive **superoxide radical (O₂⁻·)** into less reactive **hydrogen peroxide (H₂O₂)**. - It initiates the antioxidant defense but does not complete the neutralization of H₂O₂, which is handled by catalase or **glutathione peroxidase**. *Peroxidase (Incorrect)* - This is a general class of **enzymes** (e.g., **glutathione peroxidase**) that primarily use substrates like glutathione to reduce **hydrogen peroxide** or lipid peroxides to water or harmless alcohols. - It is an enzyme that works *with* antioxidants like glutathione, rather than being the major intracellular antioxidant molecule itself.

Q: A 6-month-old infant is brought to the emergency department with lethargy, vomiting, and poor feeding. The episode occurred after prolonged fasting. Laboratory results reveal hypoglycemia, low ketone levels (hypoketosis), and mild hepatomegaly. These findings suggest a defect in fat metabolism. Which of the following is the most likely underlying disorder?

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. ***Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency*** - This disorder is the most common defect of **fatty acid oxidation** and is characterized by the inability to break down medium-chain fatty acids during fasting, leading to severe **hypoglycemia**. - The hallmark finding is **hypoketosis** (low ketones), as the inability to generate acetyl-CoA from fatty acid breakdown means the substrate required for **ketogenesis** is unavailable. *Hers disease* - This is **Glycogen Storage Disease type VI**, involving a deficiency in **liver glycogen phosphorylase**, leading to impaired glycogenolysis and fasting hypoglycemia. - However, GSD type VI does not impair **beta-oxidation**; hence, patients usually maintain the ability to produce adequate **ketone bodies** during periods of fasting. *Hereditary fructose intolerance* - This disorder is a defect of **aldolase B** and causes symptoms (vomiting, lethargy, hypoglycemia) only after the introduction of **dietary fructose** or sucrose. - The acute symptoms are due to **phosphate trapping** and subsequent inhibition of gluconeogenesis, which is dependent on dietary exposure rather than prolonged fasting alone. *Glycogen storage disease type I (Von Gierke disease)* - This condition, caused by a deficiency of **glucose-6-phosphatase**, leads to profound fasting hypoglycemia, significant hepatomegaly, and **lactic acidosis**. - Unlike MCAD deficiency, Von Gierke disease primarily causes defects in glucose release but generally maintains or even increases **ketone body production** (hyperketosis) because fat breakdown is often accelerated.

Question 1

Which of the following amino acids primarily acts as a buffer in blood due to its ability to accept and donate protons at physiological pH?

Accepted Answer

Histidine

Answer

Arginine

Answer

Tryptophan

Answer

Tyrosine

Question 2

During starvation, which of the following hormones is primarily produced to maintain blood glucose levels?

Accepted Answer

Glucagon

Answer

Insulin

Answer

Cortisol

Answer

Somatostatin

Question 3

The development of cataracts in patients with Diabetes Mellitus is primarily due to the accumulation of which of the following substances in the lens?

Accepted Answer

Sorbitol

Answer

Galactitol

Answer

Fructose

Answer

Mannitol

Question 4

A patient presents with multiple colonic polyps and has been diagnosed with colorectal carcinoma. There is a strong family history of Hereditary Non-Polyposis Colorectal Cancer (HNPCC). Which DNA repair mechanism is most likely defective in this condition?

Accepted Answer

Mismatch repair

Answer

Double-strand break repair

Answer

Nucleotide excision repair

Answer

Base excision repair

Question 5

What is the primary protein that binds to thyroxine?

Accepted Answer

Thyroxine-binding globulin

Answer

Follistatin

Answer

Transthyretin

Answer

Transferrin

Question 6

A breastfed infant presents with lethargy, hepatomegaly, and cataracts. Which of the following enzyme deficiencies is most likely responsible for this presentation?

Accepted Answer

Galactose-1-phosphate uridyltransferase (GALPUT)

Answer

Galactokinase

Answer

Aldolase B

Answer

Fructokinase

Question 7

Which vitamin deficiency can lead to lactic acidosis?

Accepted Answer

Thiamine

Answer

Riboflavin

Answer

Niacin

Answer

Biotin

Question 8

Which of the following enzymes is responsible for the immortality of cancer cells?

Accepted Answer

Telomerase

Answer

RNA polymerase

Answer

Helicase

Answer

Topoisomerase

Question 9

Which of the following acts as a major intracellular antioxidant and helps in detoxifying reactive oxygen species?

Accepted Answer

Glutathione

Answer

Superoxide dismutase

Answer

Peroxidase

Answer

Catalase

Question 10

A 6-month-old infant is brought to the emergency department with lethargy, vomiting, and poor feeding. The episode occurred after prolonged fasting. Laboratory results reveal hypoglycemia, low ketone levels (hypoketosis), and mild hepatomegaly. These findings suggest a defect in fat metabolism. Which of the following is the most likely underlying disorder?

Accepted Answer

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency

Answer

Glycogen storage disease type I (Von Gierke disease)

Answer

Hers disease

Answer

Hereditary fructose intolerance

FMGE 2025 — Biochemistry