INI-CET 2025 Practice Questions

Q: What is the pH of the zwitterion as shown in the titration curve of glycine?

6. ***Correct Option: 6*** - The pH of the zwitterion corresponds to the **isoelectric point (pI)**, the pH at which the amino acid has a net charge of zero. According to the curve, this occurs at pH 5.97, which is approximately 6. - The pI is calculated as the average of the two pKa values: **pI = (pKa1 + pKa2) / 2 = (2.34 + 9.60) / 2 = 5.97**. *Incorrect Option: 4.4* - At a pH of 4.4, which is between pKa1 and pI, the glycine molecule would have a net **positive charge** as the concentration of the cationic form ([NH3+-CH2-COOH]) would still be significant. - This value does not represent any specific inflection or equivalence point on the titration curve for glycine. *Incorrect Option: 2* - A pH of approximately 2 is near the **pKa1 (2.34)** of the carboxyl group, which is the point where the concentration of the fully protonated form equals the concentration of the zwitterion. - At this pH, the molecule has a net **positive charge**, as the amino group is fully protonated and the carboxyl group is only half-deprotonated. *Incorrect Option: 9* - A pH of approximately 9 is near the **pKa2 (9.60)** of the amino group, representing the buffering region for this group. - At this pH, the molecule has a net **negative charge**, as there is a significant amount of the fully deprotonated form ([NH2-CH2-COO-]) present.

Q: The PRIMARY mechanism of toxicity of which substance is NOT through Cytochrome C oxidase inhibition?

Carbon monoxide (CO). ***Carbon monoxide (CO)*** - **Primary mechanism of toxicity** is through binding to hemoglobin forming **carboxyhemoglobin**, preventing oxygen transport - While CO can bind to **cytochrome oxidase**, its **dominant clinical effect** occurs at the oxygen delivery level, not cellular respiration *Hydrogen sulfide (H₂S)* - **Direct inhibitor** of cytochrome C oxidase by binding to the **heme iron center** - Functions similarly to cyanide, causing **histotoxic hypoxia** by blocking cellular oxygen utilization *Nitric oxide (NO)* - **Potent reversible inhibitor** of cytochrome C oxidase competing with oxygen at the active site - Physiological regulator of **cellular respiration** and important in hypoxia signaling pathways *Cyanide (CN⁻)* - **Classic inhibitor** of cytochrome C oxidase, binding with high affinity to the **oxidized cytochrome a₃** - Causes rapid **metabolic failure** by completely blocking the electron transport chain at Complex IV

Q: A 90 kg obese man is taking a carbohydrate-rich diet. Which of the following enzymes/intermediates will be elevated in him? 1. Malonyl CoA 2. Acetyl CoA Carboxylase 3. PDH 4. Citrate Lyase

$1,2,3,4$. ***Correct Answer: 1,2,3,4 (All of them)*** In an obese person consuming a carbohydrate-rich diet, **high insulin levels** drive maximum flux through **lipogenesis (fatty acid synthesis)**. This results in elevation of ALL enzymes and intermediates in the pathway: - **PDH (Pyruvate Dehydrogenase)**: Activated by insulin to convert pyruvate → Acetyl CoA in mitochondria - **Citrate Lyase**: Elevated to cleave citrate → cytosolic Acetyl CoA (substrate for fatty acid synthesis) - **Acetyl CoA Carboxylase (ACC)**: The **rate-limiting enzyme** of fatty acid synthesis, activated by insulin (dephosphorylation) and citrate - **Malonyl CoA**: The **first committed intermediate** in fatty acid synthesis, product of ACC action on Acetyl CoA All four components work sequentially in the pathway from glucose → fatty acids, and all are upregulated in this metabolic state. *Incorrect Option: 1,2,3* This incorrectly excludes **Citrate Lyase**, which is essential for providing cytosolic Acetyl CoA from mitochondrial citrate. Without elevated Citrate Lyase activity, fatty acid synthesis cannot proceed efficiently despite high carbohydrate intake. *Incorrect Option: 2,3,4* This incorrectly excludes **Malonyl CoA**, the direct product of Acetyl CoA Carboxylase and the committed intermediate for fatty acid synthesis. When ACC is highly active (as it would be with high insulin), Malonyl CoA concentration must be elevated. *Incorrect Option: 1,3,4* This incorrectly excludes **Acetyl CoA Carboxylase (ACC)**, the **rate-limiting enzyme** of the entire fatty acid synthesis pathway. In a high carbohydrate/high insulin state, ACC is maximally activated by dephosphorylation and allosteric activation by citrate, making this a critical error.

Q: Match the following blotting techniques with the type of biomolecule they detect: Blotting Technique Detects A. Southern blot 1. RNA B. Northern blot 2. Lipids C. Western blot 3. DNA D. Eastern blot 4. Protein

A-3, B-1, C-4, D-2. ***A-3, B-1, C-4, D-2*** - **Southern blot** is named after Edwin Southern and is the foundational technique used to detect specific **DNA** sequences. - **Northern blot** detects specific **RNA** sequences, while **Western blot** targets specific **Proteins** using antibodies. ***A-1, B-3, C-2, D-4*** - This option incorrectly matches Southern blot (A) with RNA (1) and Northern blot (B) with DNA (3). - The standard nomenclature links Southern with **DNA** and Northern with **RNA** due to their evolutionary development from the original technique. ***A-4, B-2, C-1, D-3*** - This option incorrectly assigns Southern blot (A) to Protein (4) and Northern blot (B) to Lipids (2). - Western blot (C) detects **Protein**, not RNA (1), as suggested here. ***A-2, B-4, C-3, D-1*** - This option incorrectly matches Southern blot (A) with Lipids (2) and Western blot (C) with DNA (3). - **Eastern blot** (D) is a technique designed to detect **post-translational modifications** (like lipids and carbohydrates) on proteins, making the D-2 match plausible, but the other matches are incorrect (i.e., **Southern blot** detects DNA).

Q: Alleles of a gene pool belong to a:

Population. ***Population (Correct)*** - A **gene pool** is the total collection of all alleles and genes within a **population** of a specific species capable of interbreeding - The concept is fundamental to **population genetics** and evolution, measuring overall genetic diversity available to the group - Includes genetic information from **all reproductive members** of the population in a geographical area *Individual (Incorrect)* - An individual possesses only a small subset of alleles from the gene pool (typically two alleles per gene locus) - Represents the **genotype** of a single organism, not the collective genetic diversity - The gene pool requires pooling genetic information from **multiple individuals** *Family (Incorrect)* - A family represents a limited subgroup within a population (related by kinship) - Does not encompass the entire **genetic variability** of the species' local reproductive unit - Too narrow a concept compared to the population-level gene pool *Cell (Incorrect)* - A cell contains the **genome** or **genotype** of an individual organism - The **gene pool** is a population-level concept extending beyond a single cell's genetic material - Represents the smallest unit of genetic information, not the collective diversity

Q: Which gene would you test if the patient has a family history of breast and ovarian cancer?

BRCA1/2. ***BRCA1/2*** - Mutations in **BRCA1** and **BRCA2** genes are responsible for the majority of hereditary breast and ovarian cancer syndromes (*Hereditary Breast and Ovarian Cancer syndrome*). [1] - Testing these genes is the standard procedure when a patient presents with a strong family history of both breast and ovarian cancers, as they are **tumor suppressor genes** involved in DNA repair. [1] ***P53*** - Mutations in the **TP53** gene are associated with **Li-Fraumeni syndrome**, which increases the risk for a wide spectrum of cancers, including breast cancer, sarcomas, brain tumors, and adrenocortical carcinoma. - While breast cancer is a component, Li-Fraumeni is less specifically linked to the combined presentation of breast and ovarian cancer compared to BRCA mutations. ***PTEN*** - Mutations in the **PTEN** gene cause **Cowden syndrome**, characterized by multiple hamartomas and an increased risk of breast, thyroid, and endometrial cancers. - Ovarian cancer is a less prominent feature of Cowden syndrome, making it a secondary consideration after BRCA testing. ***CDH1*** - Mutations in the **CDH1** gene (which encodes **E-cadherin**) are primarily associated with **Hereditary Diffuse Gastric Cancer (HDGC)**. - These mutations also confer an increased risk for **lobular breast cancer**, but they are not the primary drivers for a syndrome involving both significant breast and ovarian cancer risk.

Q: Multiple lytic lesions on skull are seen in which thyroid carcinoma?

Follicular carcinoma. ***Follicular carcinoma*** - Follicular thyroid carcinoma (FTC) classically spreads hematogenously to distant sites, most commonly the **bone (skull, spine, pelvis)** and lungs. - Bone metastases, especially in the skull, are typically **lytic** and may present as solitary or multiple lesions with a characteristic **"cannonball" appearance** on imaging if involving the lungs. ***Papillary carcinoma thyroid*** - Papillary thyroid carcinoma (PTC) predominantly spreads locally via **lymphatics** to regional neck lymph nodes, rarely causing distant metastases early in the disease course. - Distant metastases, when they occur, are usually to the lungs (small micronodules) and are less common as lytic skull lesions compared to FTC. ***Hurthle cell carcinoma*** - Hurthle cell carcinoma (a variant of follicular carcinoma) also has a high propensity for **hematogenous spread** to bone and lung. - While it can cause lytic bone lesions, it is best classified under the broader category of follicular carcinoma for its metastatic pattern, but FTC is the most common association for lytic skull lesions among the choices. ***Thyroid lymphoma*** - Thyroid lymphoma is rare and usually presents as a **rapidly enlarging thyroid mass** in an older patient, often associated with a background of Hashimoto's thyroiditis. - It typically causes diffuse thyroid involvement and local invasion into the neck structures; distant metastases, especially lytic skull lesions, are highly **uncommon**.

Q: Caspase-1 mediated cell death with inflammation is known as

Pyroptosis. ***Pyroptosis*** - This form of programmed cell death is characterized by the formation of an **inflammasome** complex [2], activating **Caspase-1** [1]. - Caspase-1 activation leads to the cleavage of pro-IL-1$\beta$ and pro-IL-18 into their active forms, resulting in a highly **inflammatory** process and cell lysis [1]. *Necroptosis* - This programmed, but non-apoptotic, cell death is mediated by the **RIPK1/RIPK3/MLKL** signaling pathway, involving receptor-interacting protein kinases [1]. - It is morphologically similar to necrosis but can be pharmacologically inhibited; it is **Caspase-independent** [3]. *Ferroptosis* - Ferroptosis is a form of regulated necrosis driven by **iron-dependent lipid peroxidation**. - It is characterized by the accumulation of reactive oxygen species and is typically **Caspase-independent**. *Necrosis* - Necrosis is an uncontrolled, **non-programmed** form of cell death resulting from acute cellular injury or pathology (e.g., ischemia). - It involves cell swelling, rupture of the plasma membrane, and leakage of cellular contents, leading to massive local inflammation, but is **not directly mediated by Caspase-1**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Cellular Responses to Stress and Toxic Insults: Adaptation, Injury, and Death, p. 71. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, p. 196. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Cellular Responses to Stress and Toxic Insults: Adaptation, Injury, and Death, pp. 69-71.

Q: Least common finding in diabetic kidney is

Armanni-Ebstein. ***Armanni-Ebstein*** - **Armanni-Ebstein lesion** (also known as Armanni-Ebstein change) refers to severe **glycogen accumulation** in the tubular epithelial cells, typically the proximal tubules. - This finding is relatively rare and seen mainly in cases of **poorly controlled acute diabetes mellitus** or acute hyperglycemia, making it the least common routine finding compared to the other structural changes. ***Podocyte loss*** - **Podocyte injury (podocytopathy)** and subsequent loss are a central and early feature in the pathogenesis of diabetic nephropathy, leading to **proteinuria**. - Progressive effacement, detachment, and eventual depletion of these highly specialized cells are constant findings in established **diabetic kidney disease (DKD)**. ***Mesangial widening*** - **Mesangial expansion/widening** is considered the earliest and most specific histological change in **diabetic nephropathy**. - This pathology progresses, leading eventually to **diffuse or nodular glomerulosclerosis** (**Kimmelstiel-Wilson lesions**), making it a universal finding in established DKD. ***GBM thickening*** - **Glomerular basement membrane (GBM) thickening** occurs very early in **diabetic nephropathy**, often preceding clinical proteinuria [1]. - It is a consistent and measurable structural abnormality caused by increased synthesis and altered composition of **extracellular matrix** components in the GBM [1], [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1119-1121. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Kidney, pp. 907-908.

Q: Which of the following tissues will not be able to take up glucose in insulin resistance/insulin absence/diabetes mellitus?

Skeletal muscle. ### **Explanation** The uptake of glucose into cells is mediated by **Glucose Transporters (GLUT)**. The fundamental concept here is the distinction between **Insulin-Dependent** and **Insulin-Independent** glucose uptake. **1. Why Skeletal Muscle is Correct:** * **Skeletal muscle** (and adipose tissue) primarily utilizes **GLUT-4**, which is the only **insulin-dependent** glucose transporter. * In the absence of insulin or in states of insulin resistance, GLUT-4 remains sequestered in intracellular vesicles and cannot translocate to the cell membrane. Consequently, these tissues cannot take up glucose effectively, leading to post-prandial hyperglycemia. **2. Why the Other Options are Incorrect:** * **Kidney (Option A):** Uses **GLUT-2** (basolateral membrane) and **SGLT-1/2** (apical membrane) for glucose reabsorption. These are insulin-independent. * **Brain (Option C):** Relies on **GLUT-1** and **GLUT-3**. The brain requires a continuous supply of glucose regardless of insulin levels to maintain metabolic function. * **Red Blood Cells (Option D):** Utilize **GLUT-1** for constitutive glucose uptake, which does not require insulin. --- ### **High-Yield Clinical Pearls for INI-CET** * **GLUT-4 Locations:** Remember the "Big Three": **Skeletal muscle**, **Cardiac muscle**, and **Adipose tissue**. * **Exercise Exception:** During exercise, skeletal muscle can take up glucose **independently of insulin** because muscle contraction triggers GLUT-4 translocation via the **AMPK pathway**. This is why exercise is a key management strategy for Type 2 Diabetes. * **GLUT-2:** Found in the **Liver, Pancreatic beta cells, and Small Intestine**. It acts as a "glucose sensor" due to its high $K_m$ (low affinity). * **SGLT:** These are **Secondary Active Transporters** (Sodium-Glucose Linked Transporters) found in the kidneys and small intestine, not to be confused with the facilitated diffusion of GLUTs.

Question 1

What is the pH of the zwitterion as shown in the titration curve of glycine?

Accepted Answer

6

Answer

2

Answer

9

Answer

4.4

Question 2

The PRIMARY mechanism of toxicity of which substance is NOT through Cytochrome C oxidase inhibition?

Accepted Answer

Carbon monoxide (CO)

Answer

Nitric oxide (NO)

Answer

Cyanide (CN)

Answer

Oligomycin

Question 3

A 90 kg obese man is taking a carbohydrate-rich diet. Which of the following enzymes/intermediates will be elevated in him? 1. Malonyl CoA 2. Acetyl CoA Carboxylase 3. PDH 4. Citrate Lyase

Accepted Answer

$1,2,3,4$

Answer

$1,2,3$

Answer

$1,3,4$

Answer

$2,3,4$

Question 4

Match the following blotting techniques with the type of biomolecule they detect: Blotting Technique Detects A. Southern blot 1. RNA B. Northern blot 2. Lipids C. Western blot 3. DNA D. Eastern blot 4. Protein

Accepted Answer

A-3, B-1, C-4, D-2

Answer

A-4, B-2, C-1, D-3

Answer

A-2, B-4, C-3, D-1

Answer

A-1, B-3, C-2, D-4

Question 5

Alleles of a gene pool belong to a:

Accepted Answer

Population

Answer

Cell

Answer

Individual

Answer

Family

Question 6

Which gene would you test if the patient has a family history of breast and ovarian cancer?

Accepted Answer

BRCA1/2

Answer

P53

Answer

CDH1

Answer

PTEN

Question 7

Multiple lytic lesions on skull are seen in which thyroid carcinoma?

Accepted Answer

Follicular carcinoma

Answer

Thyroid lymphoma

Answer

Papillary carcinoma thyroid

Answer

Hurthle cell carcinoma

Question 8

Caspase-1 mediated cell death with inflammation is known as

Accepted Answer

Pyroptosis

Answer

Necroptosis

Answer

Necrosis

Answer

Ferroptosis

Question 9

Least common finding in diabetic kidney is

Accepted Answer

Armanni-Ebstein

Answer

Podocyte loss

Answer

GBM thickening

Answer

Mesangial widening

Question 10

Which of the following tissues will not be able to take up glucose in insulin resistance/insulin absence/diabetes mellitus?

Accepted Answer

Skeletal muscle

Answer

Kidney

Answer

Brain

Answer

Red blood cells

INI-CET 2025

Biochemistry

Community Medicine

Internal Medicine

Pathology

Physiology