FMGE 2025 — Biochemistry

Q: Which of the following is excreted in the urine of patients with pentosuria?

L-Xylulose. ***L-Xylulose***- Pentosuria is a benign, autosomal recessive disorder caused by a deficiency in the enzyme **L-xylulose reductase** (or xylitol dehydrogenase), which is part of the **glucuronic acid pathway (GAA)**.- This deficiency prevents the conversion of **L-xylulose** (a pentose intermediate) to xylitol, leading to the accumulation and subsequent excretion of L-xylulose in the urine.*D-Ribose*- D-Ribose is an **aldopentose** sugar crucial for forming the backbone of **RNA**, **ATP**, and various coenzymes (e.g., NAD, FAD).- Its metabolism is primarily handled by the **pentose phosphate pathway**; its excretion is not the hallmark of the enzyme deficiency in pentosuria.*D-Ribulose*- D-Ribulose is a **ketopentose** that plays a key role as an intermediate in the **pentose phosphate pathway** (PPP), specifically forming xylulose 5-phosphate.- Although it is a pentose, its accumulation and excretion are not characteristic findings of the defective **L-xylulose reductase** enzyme in pentosuria.*D-Lactose*- D-Lactose is a **disaccharide** composed of glucose and galactose, derived from milk, and is not a pentose sugar.- Lactosuria (lactose excretion) is typically related to high dietary intake or severe disorders affecting **lactose metabolism** or hepatic function, which is unrelated to the biochemical defect causing pentosuria. [Practice more Biochemistry PYQs on OnCourse]

Q: A patient with a long-standing history of diabetes presents with cataracts. Which of the following metabolic products is primarily responsible for cataract formation in this condition?

Sorbitol. ***Sorbitol*** - When blood glucose is elevated in diabetes, the enzyme **aldose reductase** converts excess glucose into **sorbitol** (a polyol) in tissues like the lens, which do not require insulin for glucose uptake. - Sorbitol is poorly permeable across cell membranes. Its accumulation creates a significant **osmotic gradient** within the lens fibers, causing water influx and subsequent lens swelling and opacification (cataract formation). *Mannitol* - **Mannitol** is a polyol often used as an osmotic diuretic in clinical settings to reduce cerebral edema or intraocular pressure. - Although chemically similar to sorbitol, mannitol accumulation is not the primary mechanism of **cataract formation** specifically linked to chronic hyperglycemia. *Galactitol* - **Galactitol** is NOT responsible for cataract formation in diabetes, but is specifically responsible for cataracts in individuals with **galactosemia** (inability to metabolize galactose). - It is formed from **galactose** via aldose reductase, making it the incorrect metabolite in a patient with diabetes-related cataracts. *Fructose* - **Fructose** is formed when sorbitol is further metabolized by the enzyme **sorbitol dehydrogenase**. - While present in the polyol pathway, **sorbitol** itself is the product whose high intracellular concentration and osmotic activity is the direct cause of the diabetic cataract. [Practice more Biochemistry PYQs on OnCourse]

Q: A patient presents with gum bleeding, petechiae, poor wound healing, and other related symptoms. Which of the following vitamin deficiencies is most likely responsible for this presentation?

Vitamin C. ***Vitamin C*** - Vitamin C (ascorbic acid) is essential for the hydroxylation of **proline** and **lysine** residues during collagen synthesis, crucial for maintaining the integrity of blood vessels and skin. - Deficiency results in **scurvy**, characterized by defective collagen, leading to fragile capillaries (manifesting as **gum bleeding** and **petechiae**) and impaired **wound healing**. *Vitamin A* - Deficiency is primarily associated with visual disturbances, most notably **night blindness** (**nyctalopia**), and **xerophthalmia** (dry eyes). - Its main roles involve vision, epithelial differentiation, and immune function, not the stability of subendothelial collagen required to prevent bleeding tendencies described here. *Vitamin B6* - Pyridoxine deficiency symptoms include **seborrheic dermatitis**, **stomatitis**, **cheilosis**, and neurological issues like **peripheral neuropathy** and seizures in infants. - While involved in numerous metabolic pathways, its deficiency is not responsible for the characteristic symptoms of capillary fragility (petechiae and bleeding). *Vitamin B3* - Niacin deficiency causes **pellagra**, classically identified by the "3 D's": **Dermatitis** (photosensitive rash), **Diarrhea**, and **Dementia**. - Although pellagra involves epithelial changes (dermatitis), it does not typically present with the severe vascular fragility, gum manifestations, and poor generalized wound healing seen in scurvy. [Practice more Biochemistry PYQs on OnCourse]

Q: A patient presents with arthritis, and arthroscopy reveals blackening of the joints. Which enzyme deficiency is most likely responsible for this condition?

Homogentisate oxidase. ***Homogentisate oxidase***- Deficiency of this enzyme causes **Alkaptonuria**, resulting in the accumulation of **homogentisic acid**, which oxidizes into dark polymeric pigment called **ochronotic pigment**.- This pigment deposits in cartilage and connective tissues (**Ochronosis**), leading to severe destructive arthritis, especially in large joints, and causing the characteristic **blackening of joint tissues** observed on arthroscopy.*Branched-chain alpha-ketoacid dehydrogenase*- Deficiency of this enzyme causes **Maple Syrup Urine Disease (MSUD)**, leading to the accumulation of **branched-chain amino acids** (leucine, isoleucine, valine).- MSUD is characterized by severe neurologic dysfunction and a distinctive maple syrup odor in the urine, not chronic arthritis or joint pigmentation.*Tyrosinase*- This enzyme is crucial for the synthesis of **melanin** from tyrosine.- Deficiency results in conditions like **Albinism**, characterized by hypopigmentation of the skin, hair, and eyes, which is distinct from ochronotic arthritis.*Fumarase*- Deficiency of this enzyme (Fumarate hydratase) impairs the **Krebs cycle** (TCA cycle).- Clinical features include severe intellectual disability, microcephaly, and metabolic acidosis, without the development of ochronosis or black joints. [Practice more Biochemistry PYQs on OnCourse]

Q: A patient with a history of strenuous exercise skipped a meal and later consumed alcohol at a party. Alcohol inhibits which of the following biochemical processes, potentially leading to hypoglycemia?

Gluconeogenesis. ***Gluconeogenesis*** - Alcohol metabolism by **alcohol dehydrogenase** and **aldehyde dehydrogenase** generates a massive influx of **NADH**, drastically increasing the hepatic NADH/NAD+ ratio. - This high NADH/NAD+ ratio shifts metabolic intermediates, inhibiting key enzymes (e.g., **lactate dehydrogenase** and **malate dehydrogenase**) required to convert precursors like lactate and amino acids into glucose, leading to failure of new glucose synthesis and subsequent hypoglycemia. *Glycogenolysis* - This process, the breakdown of stored **glycogen** into glucose, is not directly inhibited by the increased NADH ratio produced during alcohol metabolism. - In fact, the initial phase of alcohol-induced hypoglycemia relies on the depletion of pre-existing glycogen stores, which is accelerated by factors like strenuous exercise or fasting. *Hexose Monophosphate (HMP) Shunt* - The primary function of the HMP shunt is to produce **NADPH** (for reductive biosynthesis and antioxidant defense) and five-carbon sugars (**ribose-5-phosphate**) for nucleotide synthesis. - Inhibition of the HMP shunt alters cell redox status and nucleotide production but does not directly impair blood glucose maintenance or cause acute hypoglycemia. *Ketone Body Formation* - Alcohol metabolism actually tends to **inhibit** ketone body formation because the high NADH ratio inhibits **beta-oxidation** of fatty acids in the liver, which is required to produce the Acetyl-CoA necessary for ketogenesis. - While ketone formation is inhibited, this is a consequence of high NADH, and the hypoglycemia itself results from the inability to synthesize glucose via gluconeogenesis, not the absence of ketones. [Practice more Biochemistry PYQs on OnCourse]

21 Previous Year Questions with Answers & Explanations

Questions

Which of the following is excreted in the urine of patients with pentosuria?

A patient with a long-standing history of diabetes presents with cataracts. Which of the following metabolic products is primarily responsible for cataract formation in this condition?

A patient presents with gum bleeding, petechiae, poor wound healing, and other related symptoms. Which of the following vitamin deficiencies is most likely responsible for this presentation?

A patient presents with arthritis, and arthroscopy reveals blackening of the joints. Which enzyme deficiency is most likely responsible for this condition?

A patient with a history of strenuous exercise skipped a meal and later consumed alcohol at a party. Alcohol inhibits which of the following biochemical processes, potentially leading to hypoglycemia?

Which of the following accumulates in the mucopolysaccharidosis associated with Natowicz disease?

Which of the following enzymes is dependent on Vitamin C for its activity?

Which of the following enzymes is typically elevated in prostate cancer?

Which deficiency is most likely in a patient with delayed wound healing and alopecia?

Q10

A disease with mitochondrial inheritance is inherited from which family member?

FMGE 2025 - Biochemistry FMGE Practice Questions and MCQs

Question 1: Which of the following is excreted in the urine of patients with pentosuria?

A. L-Xylulose (Correct Answer)
B. D-Lactose
C. D-Ribulose
D. D-Ribose

Explanation: ***L-Xylulose***- Pentosuria is a benign, autosomal recessive disorder caused by a deficiency in the enzyme **L-xylulose reductase** (or xylitol dehydrogenase), which is part of the **glucuronic acid pathway (GAA)**.- This deficiency prevents the conversion of **L-xylulose** (a pentose intermediate) to xylitol, leading to the accumulation and subsequent excretion of L-xylulose in the urine.*D-Ribose*- D-Ribose is an **aldopentose** sugar crucial for forming the backbone of **RNA**, **ATP**, and various coenzymes (e.g., NAD, FAD).- Its metabolism is primarily handled by the **pentose phosphate pathway**; its excretion is not the hallmark of the enzyme deficiency in pentosuria.*D-Ribulose*- D-Ribulose is a **ketopentose** that plays a key role as an intermediate in the **pentose phosphate pathway** (PPP), specifically forming xylulose 5-phosphate.- Although it is a pentose, its accumulation and excretion are not characteristic findings of the defective **L-xylulose reductase** enzyme in pentosuria.*D-Lactose*- D-Lactose is a **disaccharide** composed of glucose and galactose, derived from milk, and is not a pentose sugar.- Lactosuria (lactose excretion) is typically related to high dietary intake or severe disorders affecting **lactose metabolism** or hepatic function, which is unrelated to the biochemical defect causing pentosuria.

Question 2: A patient with a long-standing history of diabetes presents with cataracts. Which of the following metabolic products is primarily responsible for cataract formation in this condition?

A. Galactitol
B. Mannitol
C. Sorbitol (Correct Answer)
D. Fructose

Explanation: ***Sorbitol*** - When blood glucose is elevated in diabetes, the enzyme **aldose reductase** converts excess glucose into **sorbitol** (a polyol) in tissues like the lens, which do not require insulin for glucose uptake. - Sorbitol is poorly permeable across cell membranes. Its accumulation creates a significant **osmotic gradient** within the lens fibers, causing water influx and subsequent lens swelling and opacification (cataract formation). *Mannitol* - **Mannitol** is a polyol often used as an osmotic diuretic in clinical settings to reduce cerebral edema or intraocular pressure. - Although chemically similar to sorbitol, mannitol accumulation is not the primary mechanism of **cataract formation** specifically linked to chronic hyperglycemia. *Galactitol* - **Galactitol** is NOT responsible for cataract formation in diabetes, but is specifically responsible for cataracts in individuals with **galactosemia** (inability to metabolize galactose). - It is formed from **galactose** via aldose reductase, making it the incorrect metabolite in a patient with diabetes-related cataracts. *Fructose* - **Fructose** is formed when sorbitol is further metabolized by the enzyme **sorbitol dehydrogenase**. - While present in the polyol pathway, **sorbitol** itself is the product whose high intracellular concentration and osmotic activity is the direct cause of the diabetic cataract.

Question 3: A patient presents with gum bleeding, petechiae, poor wound healing, and other related symptoms. Which of the following vitamin deficiencies is most likely responsible for this presentation?

A. Vitamin B3
B. Vitamin C (Correct Answer)
C. Vitamin B6
D. Vitamin A

Explanation: ***Vitamin C*** - Vitamin C (ascorbic acid) is essential for the hydroxylation of **proline** and **lysine** residues during collagen synthesis, crucial for maintaining the integrity of blood vessels and skin. - Deficiency results in **scurvy**, characterized by defective collagen, leading to fragile capillaries (manifesting as **gum bleeding** and **petechiae**) and impaired **wound healing**. *Vitamin A* - Deficiency is primarily associated with visual disturbances, most notably **night blindness** (**nyctalopia**), and **xerophthalmia** (dry eyes). - Its main roles involve vision, epithelial differentiation, and immune function, not the stability of subendothelial collagen required to prevent bleeding tendencies described here. *Vitamin B6* - Pyridoxine deficiency symptoms include **seborrheic dermatitis**, **stomatitis**, **cheilosis**, and neurological issues like **peripheral neuropathy** and seizures in infants. - While involved in numerous metabolic pathways, its deficiency is not responsible for the characteristic symptoms of capillary fragility (petechiae and bleeding). *Vitamin B3* - Niacin deficiency causes **pellagra**, classically identified by the "3 D's": **Dermatitis** (photosensitive rash), **Diarrhea**, and **Dementia**. - Although pellagra involves epithelial changes (dermatitis), it does not typically present with the severe vascular fragility, gum manifestations, and poor generalized wound healing seen in scurvy.

Question 4: A patient presents with arthritis, and arthroscopy reveals blackening of the joints. Which enzyme deficiency is most likely responsible for this condition?

A. Fumarase
B. Tyrosinase
C. Branched-chain alpha-ketoacid dehydrogenase
D. Homogentisate oxidase (Correct Answer)

Explanation: ***Homogentisate oxidase***- Deficiency of this enzyme causes **Alkaptonuria**, resulting in the accumulation of **homogentisic acid**, which oxidizes into dark polymeric pigment called **ochronotic pigment**.- This pigment deposits in cartilage and connective tissues (**Ochronosis**), leading to severe destructive arthritis, especially in large joints, and causing the characteristic **blackening of joint tissues** observed on arthroscopy.*Branched-chain alpha-ketoacid dehydrogenase*- Deficiency of this enzyme causes **Maple Syrup Urine Disease (MSUD)**, leading to the accumulation of **branched-chain amino acids** (leucine, isoleucine, valine).- MSUD is characterized by severe neurologic dysfunction and a distinctive maple syrup odor in the urine, not chronic arthritis or joint pigmentation.*Tyrosinase*- This enzyme is crucial for the synthesis of **melanin** from tyrosine.- Deficiency results in conditions like **Albinism**, characterized by hypopigmentation of the skin, hair, and eyes, which is distinct from ochronotic arthritis.*Fumarase*- Deficiency of this enzyme (Fumarate hydratase) impairs the **Krebs cycle** (TCA cycle).- Clinical features include severe intellectual disability, microcephaly, and metabolic acidosis, without the development of ochronosis or black joints.

Question 5: A patient with a history of strenuous exercise skipped a meal and later consumed alcohol at a party. Alcohol inhibits which of the following biochemical processes, potentially leading to hypoglycemia?

A. Glycogenolysis
B. Ketone Body Formation
C. Gluconeogenesis (Correct Answer)
D. Hexose Monophosphate (HMP) Shunt

Explanation: ***Gluconeogenesis*** - Alcohol metabolism by **alcohol dehydrogenase** and **aldehyde dehydrogenase** generates a massive influx of **NADH**, drastically increasing the hepatic NADH/NAD+ ratio. - This high NADH/NAD+ ratio shifts metabolic intermediates, inhibiting key enzymes (e.g., **lactate dehydrogenase** and **malate dehydrogenase**) required to convert precursors like lactate and amino acids into glucose, leading to failure of new glucose synthesis and subsequent hypoglycemia. *Glycogenolysis* - This process, the breakdown of stored **glycogen** into glucose, is not directly inhibited by the increased NADH ratio produced during alcohol metabolism. - In fact, the initial phase of alcohol-induced hypoglycemia relies on the depletion of pre-existing glycogen stores, which is accelerated by factors like strenuous exercise or fasting. *Hexose Monophosphate (HMP) Shunt* - The primary function of the HMP shunt is to produce **NADPH** (for reductive biosynthesis and antioxidant defense) and five-carbon sugars (**ribose-5-phosphate**) for nucleotide synthesis. - Inhibition of the HMP shunt alters cell redox status and nucleotide production but does not directly impair blood glucose maintenance or cause acute hypoglycemia. *Ketone Body Formation* - Alcohol metabolism actually tends to **inhibit** ketone body formation because the high NADH ratio inhibits **beta-oxidation** of fatty acids in the liver, which is required to produce the Acetyl-CoA necessary for ketogenesis. - While ketone formation is inhibited, this is a consequence of high NADH, and the hypoglycemia itself results from the inability to synthesize glucose via gluconeogenesis, not the absence of ketones.

Question 6: Which of the following accumulates in the mucopolysaccharidosis associated with Natowicz disease?

A. Dermatan sulfate
B. Hyaluronic acid (Correct Answer)
C. Heparan sulfate
D. Keratan sulfate

Explanation: ***Hyaluronic acid***- Natowicz disease is synonymous with **Mucopolysaccharidosis type IX (MPS IX)**, a highly rare lysosomal storage disorder.- This condition is caused by a deficiency in the enzyme **hyaluronidase (HYAL1)**, which results in the failure to degrade **hyaluronic acid**, leading to its massive accumulation.*Dermatan sulfate*- Accumulation of **dermatan sulfate** is the defining characteristic of MPS I (Hurler, Scheie), MPS II (Hunter), and MPS VI (Maroteaux-Lamy).- These disorders generally involve widespread visceral, skeletal, and neurological pathology, unlike the localized features of MPS IX.*Heparan sulfate*- **Heparan sulfate** accumulates primarily in the various subtypes of **Sanfilippo syndrome (MPS III)**, as well as MPS I and II.- MPS III is predominantly characterized by progressive **neurocognitive decline** with relatively mild somatic features compared to other MPS types.*Keratan sulfate*- Accumulation of **keratan sulfate** is the metabolic hallmark of **Morquio syndrome (MPS IV)**, a disorder primarily presenting with severe skeletal dysplasia.- MPS IV involves deficiencies in either *N*-acetylgalactosamine-6-sulfatase or $\beta$-galactosidase, not hyaluronidase.

Question 7: Which of the following enzymes is dependent on Vitamin C for its activity?

A. Lysyl oxidase
B. Prolyl hydroxylase (Correct Answer)
C. Lysyl dehydrogenase
D. Hydroxyprolyl kinase

Explanation: ***Prolyl hydroxylase***- **Prolyl hydroxylase** requires **Vitamin C** (ascorbic acid) to reduce the ferric iron (Fe3+) in its active site back to **ferrous iron (Fe2+),** thereby maintaining its catalytic function.- This enzyme hydroxylates **proline** residues, a critical post-translational modification necessary for the stabilization and proper triple-helical winding of **collagen**; deficiency results in **scurvy**. *Lysyl dehydrogenase*- This enzyme is involved in **lysine catabolism** via deamination and is generally not associated with the direct role of Vitamin C in collagen synthesis.- It is distinct from **lysyl hydroxylase**, which *is* a Vitamin C-dependent enzyme modifying lysine in collagen. *Lysyl oxidase*- **Lysyl oxidase** is responsible for forming covalent **cross-links** between collagen and elastin molecules, stabilizing the extracellular matrix structure.- This enzyme requires **copper** (Cu2+) as a cofactor for its activity and is not directly dependent on Vitamin C. *Hydroxyprolyl kinase*- This is not a standard physiological enzyme involved in the key metabolic pathways of **collagen synthesis** or degradation.- Kinase activity concerns **phosphorylation**, which is unrelated to the **hydroxylation** mechanism essential for Vitamin C dependence in connective tissue metabolism.

Question 8: Which of the following enzymes is typically elevated in prostate cancer?

A. Alpha-fetoprotein
B. Lactate dehydrogenase
C. Alkaline phosphatase
D. Acid phosphatase (Correct Answer)

Explanation: ***Acid phosphatase***- While largely replaced by **Prostate-Specific Antigen (PSA)** for screening, **Prostatic Acid Phosphatase (PAP)** remains a strong enzymatic marker for prostate cancer, particularly useful in monitoring metastatic disease.- Significant elevations are often indicative of **extra-capsular extension** or **bone metastases** in advanced disease.*Alkaline phosphatase*- While generalized **Alkaline phosphatase (ALP)** can be elevated in prostate cancer, this is primarily due to **osteoblastic bone metastases**, not the tumor cells directly.- ALP is a non-specific marker primarily associated with **liver** or **generalized bone disease**.*Lactate dehydrogenase*- **Lactate dehydrogenase (LDH)** is a non-specific indicator of generalized **tissue injury** or high **tumor burden** across various malignancies (e.g., lymphomas, melanoma, germ cell tumors).- Its elevation reflects high cellular turnover/necrosis but is not a primary diagnostic marker specific to prostate cancer.*Alpha-fetoprotein*- **Alpha-fetoprotein (AFP)** is a crucial tumor marker for **hepatocellular carcinoma (HCC)** and **nonseminomatous testicular germ cell tumors** (like yolk sac tumors).- It is not typically elevated in prostate cancer and should not be used in its diagnosis or monitoring.

Question 9: Which deficiency is most likely in a patient with delayed wound healing and alopecia?

A. Calcium
B. Zinc (Correct Answer)
C. Copper
D. Vitamin D

Explanation: ***Zinc*** - **Zinc** is vital for numerous enzymatic reactions involved in protein synthesis, immune function, and cell membrane stability, impairment of which severely delays **wound healing** and tissue repair. - **Alopecia** is a classic dermatologic finding in zinc deficiency, often accompanied by **acrodermatitis enteropathica** (perioral and acral cutaneous lesions). - The combination of delayed wound healing and alopecia is highly characteristic of zinc deficiency. *Copper* - Copper deficiency typically manifests with **microcytic anemia** (refractory to iron) and **neutropenia** due to its role in iron metabolism and hematopoiesis. - While severe copper deficiency can rarely cause hair abnormalities (often described as "kinky hair" or hypopigmentation), it does not characteristically cause the combination of delayed wound healing and alopecia. - Neurological manifestations (myelopathy, peripheral neuropathy) are more prominent in copper deficiency. *Calcium* - Calcium deficiency primarily affects **bone health** (osteoporosis, osteomalacia) and **neuromuscular function** (tetany, paresthesias, seizures). - It does not typically cause delayed wound healing or alopecia. *Vitamin D* - Vitamin D deficiency mainly causes **musculoskeletal problems** (rickets in children, osteomalacia in adults, bone pain, muscle weakness). - While it has roles in immune function, it is not classically associated with the specific combination of delayed wound healing and alopecia.

Question 10: A disease with mitochondrial inheritance is inherited from which family member?

A. Father
B. Mother (Correct Answer)
C. Both mother and father
D. Grandmother (paternal)

Explanation: ***Mother*** - Mitochondrial inheritance is characterized by **maternal transmission** because almost all mitochondria in the zygote are derived from the **oocyte** (mother's egg cell). - Therefore, an affected mother will pass the disease to all of her children (sons and daughters), irrespective of sex. *Grandmother (paternal)* - The paternal grandmother passes her mitochondria to the **father**, but the father cannot transmit them to his offspring. - Inheritance is strictly maternal, meaning the genetic input from the paternal line (including the paternal grandmother) is **irrelevant** for mitochondrial DNA. *Father* - The **sperm contributes negligible mitochondrial DNA** to the fertilized egg; hence, fathers cannot pass on mitochondrial diseases to their children. - Paternal mitochondria are typically **ubiquitinated and degraded** following fertilization. *Both mother and father* - Inheritance from both parents is characteristic of **nuclear DNA** (Mendelian) disorders, such as autosomal dominant or recessive patterns. - Mitochondrial inheritance is distinctively **uniparental** and does not involve DNA contribution from both parents.