FMGE 2023 — Biochemistry
15 Previous Year Questions with Answers & Explanations
In the liver, the Apo-B gene is completely translated to ApoB-100; in the intestine, it is translated to ApoB-48. Which of the following mechanism explains this?
Hemoglobin with iron in ferric form is
Which of the following immunoglobulins shows the highest concentration in serum?
Which among the following helps in the maturation of collagen?
Which of the following cell pathways occurs exclusively in cell cytoplasm?
Nitric oxide is synthesized from which of the following amino acids?
Identify the type of inhibition shown in the graph.
Which source and cell produce testosterone?
A 68-year-old female patient has had a diabetic cataract for 3 months. Accumulation of which of the following substances is responsible for this?
Which of the following correctly represents the effect of the mutation causing sickle cell anemia?
FMGE 2023 - Biochemistry FMGE Practice Questions and MCQs
Question 1: In the liver, the Apo-B gene is completely translated to ApoB-100; in the intestine, it is translated to ApoB-48. Which of the following mechanism explains this?
- A. RNA editing (Correct Answer)
- B. Gene splicing
- C. Alternative polyadenylation
- D. Gene rearrangements
Explanation: ***RNA editing (Correct Answer)*** - This post-transcription modification involves a specific **cytidine deaminase** enzyme (APOBEC-1) found primarily in the intestine. - This enzyme converts a **CAA codon** (coding for Glutamine) into a **UAA stop codon** within the *ApoB* mRNA, truncating the protein from ApoB-100 to **ApoB-48**. *Gene splicing* - Gene splicing, including **alternative splicing**, involves differential removal of **introns** and joining of **exons** to create various mRNA transcripts from a single gene. - However, gene splicing does not involve the direct **nucleotide change** (C to U) necessary to create the premature stop codon responsible for shortening ApoB. *Alternative polyadenylation* - This process selects different cleavage sites towards the 3' end of the mRNA, influencing the length of the **3' untranslated region** and mRNA stability. - While it affects mRNA processing, it does not involve a **base conversion** that fundamentally alters the coding sequence by introducing a stop codon. *Gene rearrangements* - Gene rearrangements involve physical changes to the **genomic DNA** sequence itself (e.g., V(D)J recombination in immunoglobulins) and are typically irreversible. - The distinction between ApoB-100 and ApoB-48 is purely a **post-transcriptional** event changing the mRNA, not an alteration of the ApoB gene structure.
Question 2: Hemoglobin with iron in ferric form is
- A. Methemoglobin (Correct Answer)
- B. HbA
- C. Fetal hemoglobin
- D. HbS
Explanation: ***Methemoglobin***- **Methemoglobin** is characterized by the presence of iron in the **ferric state ($\text{Fe}^{3+}$)** in the heme group, which **cannot reversibly bind oxygen**, unlike the ferrous form. - This oxidized form of hemoglobin cannot function as an **oxygen carrier** and its accumulation leads to clinical conditions like **methemoglobinemia**. *HbA*- **HbA** (Adult hemoglobin) is the predominant form of hemoglobin in adults, and its iron must be in the **ferrous state ($\text{Fe}^{2+}$)** to bind and transport oxygen effectively.- The conversion of $\text{Fe}^{2+}$ to $\text{Fe}^{3+}$ in normal HbA is constantly prevented by the **methemoglobin reductase system** (especially **NADH-cytochrome $b_5$ reductase**). *Fetal hemoglobin*- **Fetal hemoglobin (HbF)**, like HbA, uses iron in the **ferrous state ($\text{Fe}^{2+}$)** for reversible oxygen binding, reflecting its normal physiological function in the fetus. - HbF's unique feature is its structure ($\text{alpha}_2\text{gamma}_2$) which confers a **higher affinity for oxygen** by binding **2,3-BPG** less avidly than HbA, but this does not involve ferric iron. *HbS*- **HbS** (Sickle hemoglobin) is defective due to a mutation in the **beta-globin chain** (E6V), but the iron in its heme group remains in the **functional ferrous state ($\text{Fe}^{2+}$)**.- The abnormality in HbS relates to its **polymerization** upon deoxygenation, causing red blood cell sickling, not an oxidation state change of the heme iron.
Question 3: Which of the following immunoglobulins shows the highest concentration in serum?
- A. IgG (Correct Answer)
- B. IgM
- C. IgA
- D. IgE
Explanation: ***IgG*** - **IgG** accounts for approximately **75-80%** of the total immunoglobulins in human serum, making it the highest in concentration.- Its high levels reflect its crucial roles in providing **long-term humoral immunity**, neutralizing toxins, and being the only class able to cross the **placenta** to confer passive immunity to the fetus.*IgM* - **IgM** is present at much lower concentrations (about 5-10%); it is primarily known for being the first antibody produced during a **primary immune response**. - Although it is the largest immunoglobulin (a pentamer) and effective at complement activation, its total serum concentration is substantially less than IgG.*IgA* - **IgA** constitutes about 10-15% of serum immunoglobulins, ranking second to IgG in concentration. - While abundant in serum, its primary functional significance lies in its dimeric form (**Secretory IgA**) found in mucosal secretions, protecting epithelial surfaces.*IgE* - **IgE** is the immunoglobulin present at the lowest serum concentration (trace amounts). - It is mainly bound to **mast cells** and **basophils** and is responsible for mediating immediate **Type I hypersensitivity** reactions (allergies).
Question 4: Which among the following helps in the maturation of collagen?
- A. Proline
- B. Copper and zinc
- C. Ascorbic acid (Correct Answer)
- D. Phenylalanine
Explanation: ***Ascorbic acid***- Ascorbic acid (Vitamin C) is an essential cofactor for **prolyl hydroxylase** and **lysyl hydroxylase** enzymes, which hydroxylate proline and lysine residues in procollagen.- This **hydroxylation** is critical for stabilizing the collagen triple helix structure, a necessary step for proper collagen maturation and secretion.*Proline*- **Proline** (along with glycine and lysine) is a major amino acid component of the **collagen triple helix structure**.- While essential for collagen synthesis, proline itself is a substrate, not the **cofactor** required for the crucial hydroxylation steps necessary for maturation stabilization.*Copper and zinc*- **Copper** is a required cofactor for **lysyl oxidase**, the enzyme responsible for creating *covalent cross-links* between collagen molecules, which is a late-stage event for tensile strength.- Although cross-linking is part of the overall maturation process (extracellular), **ascorbic acid's** role in the intracellular hydroxylation of procollagen is a more fundamental step in maturation.*Phenylalanine*- **Phenylalanine** is an essential aromatic amino acid primarily used in protein synthesis and as a precursor for **tyrosine**.- It plays no direct role as a **cofactor** or required structural component in the specialized post-translational modification and subsequent maturation of collagen.
Question 5: Which of the following cell pathways occurs exclusively in cell cytoplasm?
- A. TCA cycle
- B. Glycolysis (Correct Answer)
- C. Urea cycle
- D. Beta oxidation
Explanation: ***Glycolysis***- Glycolysis is the metabolic pathway converting **glucose** to **pyruvate** and occurs entirely within the **cytoplasm** (cytosol) [1].- This pathway is crucial for producing ATP both in the presence (aerobic) and absence (anaerobic) of oxygen [3].*Beta oxidation*- **Beta oxidation**, the breakdown of fatty acids, occurs primarily within the **mitochondrial matrix**.- Long-chain fatty acid activation occurs in the cytosol, but the subsequent oxidative steps are confined to the **mitochondria**.*TCA cycle*- The **TCA cycle** (Krebs cycle) is located exclusively within the **mitochondrial matrix** in eukaryotic cells.- It is responsible for the complete oxidation of acetyl-CoA, producing electron carriers like **NADH** and **FADH2**.*Urea cycle*- The **urea cycle** occurs across **two distinct cellular compartments**: reactions take place in both the **mitochondrial matrix** and the **cytosol** [2].- Specifically, the synthesis of **carbamoyl phosphate** and citrulline occurs in the mitochondria [2].
Question 6: Nitric oxide is synthesized from which of the following amino acids?
- A. Tryptophan
- B. Lysine
- C. Arginine (Correct Answer)
- D. Tyrosine
Explanation: ***Arginine*** - **L-arginine** is the sole biological precursor for nitric oxide (NO), a crucial signaling molecule involved in vasodilation, neurotransmission, and immune response. - The synthesis is catalyzed by the family of enzymes known as **nitric oxide synthases (NOS)**, which convert L-arginine into NO and **L-citrulline**. *Tryptophan* - Tryptophan is an essential amino acid that serves primarily as the precursor for the synthesis of the neurotransmitter **serotonin** and the hormone **melatonin**. - It is metabolized via the **kynurenine pathway** and is not utilized in the reaction catalyzed by NOS. *Lysine* - Lysine is an essential amino acid important for protein synthesis, and it is a precursor for **carnitine**, which is vital for fatty acid metabolism. - It is a basic amino acid and is not the substrate required by nitric oxide synthase for NO generation. *Tyrosine* - Tyrosine is the precursor amino acid necessary for the synthesis of **catecholamines** (dopamine, norepinephrine, epinephrine) and the **thyroid hormones**. - Though part of various metabolic pathways, it is not involved in the direct enzymatic conversion that yields nitric oxide.
Question 7: Identify the type of inhibition shown in the graph.
- A. Competitive inhibition
- B. Allosteric Inhibition
- C. Uncompetitive inhibition
- D. Noncompetitive inhibition (Correct Answer)
Explanation: ***Noncompetitive inhibition***- This inhibition type is characterized by a decrease in **$V_{max}$** but no change in the **$K_m$** value, meaning the inhibitor reduces the enzyme's efficiency but not its affinity for the substrate.- The inhibitor typically binds reversibly to an **allosteric site** (not the active site), affecting the enzyme's catalytic functionality whether the substrate is bound or not.*Competitive inhibition*- Competitive inhibition is characterized by an **increased $K_m$** (decreased apparent affinity) while the **$V_{max}$** remains unchanged.- The inhibitor binds directly to the **active site**, competing with the substrate, and the effect can be overcome by increasing substrate concentration.*Allosteric Inhibition*- Allosteric inhibition is a general mechanism where a molecule binds to a site other than the active site (**allosteric site**), changing the enzyme's conformation and activity.- While noncompetitive and uncompetitive inhibitions are types of allosteric regulation, "noncompetitive inhibition" is the specific and most accurate term for the observed kinetic behavior (decreased $V_{max}$, constant $K_m$).*Uncompetitive inhibition*- This type involves the inhibitor binding only to the **enzyme-substrate complex (ES)**, resulting in a proportional decrease in both **$V_{max}$** and **$K_m$**.- On a Lineweaver-Burk plot, this is shown by parallel lines, highly distinguishing it from noncompetitive inhibition where the lines intersect on the X-axis.
Question 8: Which source and cell produce testosterone?
- A. Dihydrotestosterone and Leydig cells
- B. FSH and Leydig cells
- C. Cholesterol and Leydig cells (Correct Answer)
- D. Cholesterol and Sertoli cells
Explanation: ***Cholesterol and Leydig cells***- **Testosterone** is a steroid hormone, and like all steroid hormones (glucocorticoids, mineralocorticoids, estrogen), it is derived from the precursor molecule, **cholesterol**.- The primary source of testosterone production in the male testes is the **Leydig cells** (interstitial cells), stimulated by **Luteinizing Hormone (LH)**.*Cholesterol and Sertoli cells*- While **cholesterol** is the accurate precursor (source), **Sertoli cells** are mainly responsible for supporting **spermatogenesis** and producing **androgen-binding protein (ABP)** and **inhibin**.- Sertoli cells regulate the testicular microenvironment and are primarily stimulated by **FSH**, not for testosterone synthesis.*Dihydrotestosterone and Leydig cells*- **Dihydrotestosterone (DHT)** is a potent *metabolite* formed from testosterone via the enzyme **5-alpha reductase**, not the precursor for testosterone synthesis itself.- Although **Leydig cells** are the site of testosterone production, the initial source must be **cholesterol**, making DHT incorrect.*FSH and Leydig cells*- **FSH** (Follicle-Stimulating Hormone) primarily targets the **Sertoli cells** to promote sperm development and inhibin production.- The pituitary hormone that stimulates **Leydig cells** to synthesize testosterone from cholesterol is **Luteinizing Hormone (LH)**.
Question 9: A 68-year-old female patient has had a diabetic cataract for 3 months. Accumulation of which of the following substances is responsible for this?
- A. Fructose
- B. Lactose + Glucose
- C. Sorbitol + Fructose (Correct Answer)
- D. Glucose
Explanation: ***Sorbitol + Fructose*** This option correctly identifies the products of the **polyol pathway**, which is significantly activated in lens fibers during **hyperglycemia**. **Sorbitol** is the key substance that accumulates due to high **aldose reductase** activity and low sorbitol dehydrogenase activity, leading to an **osmotic gradient** and water accumulation, causing lens swelling and opacification (cataract). *Glucose* Although high blood **glucose** initiates the process by serving as the substrate for aldose reductase, glucose itself is not the primary substance responsible for the osmotic damage in the lens. In normal lens metabolism, glucose is primarily metabolized via **glycolysis**; only when levels are excessive is the polyol pathway significantly utilized. *Fructose* Fructose is the breakdown product of **sorbitol** (catalyzed by sorbitol dehydrogenase), but its concentration is typically much lower than sorbitol in the lens. **Sorbitol** accumulation is the primary driver of the powerful osmotic effect that leads to water influx into the lens fiber cells and subsequent cataract formation. *Lactose + Glucose* Accumulation of **lactose** is not associated with diabetic cataract; this combination is irrelevant to the pathogenesis of hyperglycemia-induced lens damage. **Galactosemic cataract**, a different type of osmotic cataract, is caused by the accumulation of **galactitol** (a polyol derived from galactose, not glucose).
Question 10: Which of the following correctly represents the effect of the mutation causing sickle cell anemia?
- A. Glutamate by valine at the 5th position
- B. Valine by glutamate at the 5th position
- C. Valine by glutamate at the 6th position
- D. Glutamate by valine at the 6th position (Correct Answer)
Explanation: ***Glutamate by valine at the 6th position***- This mutation involves a single nucleotide substitution (A to T) in the $\beta$-globin gene, resulting in the replacement of hydrophilic **glutamate** with hydrophobic **valine** at the sixth position.- This change (E6V) creates a sticky patch on the **hemoglobin S (HbS)** molecule, leading to polymerization and sickling of red blood cells under conditions of low oxygen tension.*Valine by glutamate at the 6th position*- This represents the reverse substitution: replacing **valine** with **glutamate** at the 6th position.- This reversal of the substitution direction would describe the change from **HbS** back to the normal $\beta$-globin chain structure (**HbA**), not the cause of sickle cell anemia.*Glutamate by valine at the 5th position*- Although the amino acid substitution (**Glutamate** replaced by **Valine**) is correct, the position specified is inaccurate.- The critical substitution causing **sickle cell disease** is precisely at the **6th position** of the $\beta$-globin chain, not the 5th.*Valine by glutamate at the 5th position*- This option fails on two counts: the substitution direction is reversed (Valine $\rightarrow$ Glutamate), and the position of the mutation (**5th**) is incorrect.- The pathogenesis of sickle cell anemia depends on the replacement of the charged hydrophilic amino acid (**glutamate**) with the uncharged hydrophobic amino acid (**valine**) at position 6.