Enzymes

Enzymes Indian Medical PG Question 1: Which of the following statements about alcoholic hepatitis is false?

• A. Gamma glutamyl transferase is raised
• B. Alkaline phosphatase is raised
• C. SGOT is raised > SGPT
• D. SGPT is raised > SGOT (Correct Answer)

Enzymes Explanation: ***SGPT is raised > SGOT*** - In **alcoholic hepatitis**, the ratio of **AST (SGOT)** to **ALT (SGPT)** is typically **2:1 or higher**, meaning SGOT is usually significantly higher than SGPT. - This is because alcohol depletes **pyridoxal phosphate**, a cofactor for ALT, leading to relatively lower ALT levels. *Gamma glutamyl transferase is raised* - **Gamma-glutamyl transferase (GGT)** is frequently elevated in **alcoholic liver disease**, including alcoholic hepatitis [1]. - It serves as a sensitive marker for **biliary tract injury** and **alcohol consumption** [1]. *SGOT is raised > SGPT* - This statement is **true** for alcoholic hepatitis, as the **AST (SGOT)** to **ALT (SGPT)** ratio is typically **2:1 or greater**. - The disproportionately high AST is a characteristic feature reflecting the **mitochondrial damage** caused by alcohol within hepatocytes [2]. *Alkaline phosphatase is raised* - **Alkaline phosphatase (ALP)** can be elevated in alcoholic hepatitis, although usually to a lesser extent than in obstructive jaundice [1]. - Its elevation often reflects superimposed **cholestasis** or **biliary inflammation** [1].

Enzymes Indian Medical PG Question 2: Which of the following is a defining characteristic of all serine proteases?

• A. Tight binding of pancreatic trypsin inhibitor is characteristic of all serine proteases.
• B. Cleavage of peptide bonds adjacent to serine residues.
• C. Presence of Ser-His-Asp catalytic triad at the active site. (Correct Answer)
• D. Autocatalytic activation of zymogen precursors.

Enzymes Explanation: ***Presence of Ser-His-Asp catalytic triad at the active site.*** - All **serine proteases** utilize a unique **catalytic triad** composed of **serine**, **histidine**, and **aspartate** residues in their active site to perform catalysis. - This specific arrangement of amino acids enables the serine residue to act as a **nucleophile**, facilitating the cleavage of peptide bonds. *Tight binding of pancreatic trypsin inhibitor is characteristic of all serine proteases.* - The **pancreatic trypsin inhibitor (BPTI)** specifically inhibits **trypsin**, a particular serine protease, but not all members of the serine protease family. - While it's an important regulatory mechanism for trypsin, it is not a universal characteristic that defines *all* serine proteases. *Cleavage of peptide bonds adjacent to serine residues.* - Serine proteases cleave peptide bonds, but the cleavage occurs adjacent to specific amino acid residues determined by the **specificity pocket** of each individual protease, not necessarily adjacent to serine residues. - For example, trypsin cleaves after **lysine** or **arginine**, while chymotrypsin cleaves after **aromatic residues**. *Autocatalytic activation of zymogen precursors is a common feature.* - Many serine proteases are synthesized as inactive **zymogens** and activated by **proteolytic cleavage**, which can sometimes be autocatalytic. - However, not all serine proteases are produced as zymogens, and their activation mechanisms can vary, making this a common feature but not a defining characteristic of *all* of them.

Enzymes Indian Medical PG Question 3: A patient presents 12 hours following a myocardial infarction. Which of the following enzymes will be elevated at this period?

• A. Lactate dehydrogenase
• B. Creatine phosphokinase (Correct Answer)
• C. Myoglobin
• D. Serum glutamate oxaloacetate transferase (SGOT)

Enzymes Explanation: ***Creatine phosphokinase*** - **Creatine phosphokinase (CK-MB)** levels begin to rise within **3-6 hours** after an MI, peak at **12-24 hours**, and return to baseline within **48-72 hours**. - At 12 hours post-MI, CK-MB would be significantly elevated and near its peak, making it the most reliable marker for diagnosis at this timepoint. *Lactate dehydrogenase* - **Lactate dehydrogenase (LDH)** levels rise much later, typically around **24-48 hours** after an MI, and peak at **3-6 days**. - At 12 hours post-MI, LDH elevation would be minimal or non-existent. *Myoglobin* - **Myoglobin** is one of the earliest markers to rise, appearing within **1-4 hours** post-MI and peaking around **6-7 hours**. - While elevated at 12 hours, it may already be declining, and it **lacks cardiac specificity** (also released from skeletal muscle injury), making it less reliable than CK-MB for MI diagnosis. *Serum glutamate oxaloacetate transferase (SGOT)* - **SGOT (AST)** levels start to rise around **6-12 hours** post-MI, peak at **18-36 hours**, and return to normal within **3-7 days**. - While it would be beginning to rise at 12 hours, **CK-MB** is more elevated and more specific for cardiac injury at this timepoint.

Enzymes Indian Medical PG Question 4: Identify the false statement regarding suicide inhibition

• A. The binding of the enzyme to the substrate analogue is irreversible
• B. The inhibitor forms a product with the enzyme and the product inhibits it
• C. The inhibitor can bind with any site resulting in suicidal inhibition (Correct Answer)
• D. They are enzyme specific and used in rational drug design

Enzymes Explanation: ***The inhibitor can bind with any site resulting in suicidal inhibition*** - Suicide inhibition, also known as **mechanism-based inhibition**, is highly specific and requires the inhibitor to bind to the **active site** of the enzyme. - The enzyme then catalyzes a transformation of the inhibitor into a **reactive intermediate** that irreversibly binds to the active site. *The binding of the enzyme to the substrate analogue is irreversible* - This statement is true; once the suicide inhibitor is metabolically activated by the enzyme, it forms a **covalent bond** with a residue in the active site. - This irreversible binding permanently inactivates the enzyme. *The inhibitor forms a product with the enzyme and the product inhibits it* - This statement is true; the enzyme's catalytic action converts the inhibitor (a substrate analogue) into a **highly reactive compound**. - This reactive product then binds covalently and irreversibly to the enzyme's **active site**, leading to its inactivation. *They are enzyme specific and used in rational drug design* - This statement is true; suicide inhibitors are designed to be highly specific for a particular enzyme, as they rely on that enzyme's catalytic mechanism for their activation. - Their specificity and irreversible action make them valuable tools in **drug discovery** and **rational drug design**, allowing for targeted inactivation of disease-related enzymes.

Enzymes Indian Medical PG Question 5: Which is not a component of Ranson's criteria for acute pancreatitis?

• A. Serum lipase (Correct Answer)
• B. Age
• C. Base deficit
• D. Blood glucose

Enzymes Explanation: ***Serum lipase*** - **Serum lipase** is not a component of Ranson's criteria. While it is a crucial diagnostic marker for acute pancreatitis, Ranson's criteria focus on other clinical and laboratory values for predicting severity. - The criteria were developed before widespread availability and use of lipase as a primary diagnostic marker for pancreatitis. *Age* - **Age** is a component of Ranson's criteria, specifically "Age > 55 years" for admission and initial assessment [1]. - Older age is associated with increased severity and mortality in acute pancreatitis due to decreased physiologic reserve [1]. *Base deficit* - **Base deficit** is a component of Ranson's criteria, specifically "Base deficit > 4 mEq/L" after 48 hours. - A significant base deficit indicates **metabolic acidosis**, which is a marker of severe systemic inflammation and organ dysfunction in acute pancreatitis. *Blood glucose* - **Blood glucose** is a component of Ranson's criteria, specifically "Blood glucose > 200 mg/dL (11.1 mmol/L)" for admission and initial assessment. - Elevated blood glucose can reflect the severity of pancreatic inflammation and insult to the **islet cells**, or systemic stress response.

Enzymes Indian Medical PG Question 6: Phosphofructokinase-1 occupies a key position in regulating glycolysis and is also subjected to feedback control. Which among the following are the allosteric activators of phosphofructokinase-1?

• A. 2,3-Bisphosphoglycerate (2,3-BPG)
• B. Fructose 2,6-bisphosphate (Correct Answer)
• C. Glucokinase
• D. Phosphoenolpyruvate (PEP)

Enzymes Explanation: ***Fructose 2,6-bisphosphate*** - **Fructose 2,6-bisphosphate** is a potent **allosteric activator** of **phosphofructokinase-1 (PFK-1)**, increasing its affinity for fructose 6-phosphate and overcoming ATP inhibition. - Its synthesis is regulated by **insulin** (stimulating) and **glucagon** (inhibiting), linking glucose availability to glycolytic flux. *2,3-Bisphosphoglycerate (2,3-BPG)* - **2,3-BPG** is an important regulator of **hemoglobin oxygen affinity** in red blood cells. - It is not an allosteric activator of **PFK-1**; its primary role is in oxygen delivery. *Glucokinase* - **Glucokinase** is an **enzyme** in glycolysis, specifically catalyzing the phosphorylation of glucose to glucose 6-phosphate in the liver and pancreatic beta cells. - It is not an allosteric activator of **PFK-1** but rather an upstream enzyme in the pathway. *Phosphoenolpyruvate (PEP)* - **PEP** is an intermediate in glycolysis, formed from 2-phosphoglycerate and converted to pyruvate by pyruvate kinase. - It acts as an **allosteric inhibitor** of phosphofructokinase-1, signaling high energy status and slowing down glycolysis.

Enzymes Indian Medical PG Question 7: Which of the following statements is true about first-order kinetics?

• A. The half-life increases with an increase in dose.
• B. The rate of elimination is proportional to the plasma concentration. (Correct Answer)
• C. A constant amount is eliminated in unit time.
• D. The elimination follows zero-order kinetics at therapeutic doses.

Enzymes Explanation: ***The rate of elimination is proportional to the plasma concentration.*** - In **first-order kinetics**, a **constant fraction** of the drug is eliminated per unit of time, meaning that the higher the plasma concentration, the faster the elimination rate. - This principle ensures that the drug concentration decreases exponentially over time, as the amount eliminated is always a percentage of the remaining drug. - The rate equation is: dC/dt = -kC, where the rate is directly proportional to concentration. *The half-life increases with an increase in dose.* - This statement is incorrect because, for **first-order kinetics**, the **half-life remains constant** regardless of the dose or the initial concentration of the drug. - The time it takes for the plasma concentration to halve is independent of the initial amount. *The elimination follows zero-order kinetics at therapeutic doses.* - This is incorrect. **First-order kinetics** is the most common pattern for drug elimination at **therapeutic doses**. - **Zero-order kinetics** occurs when elimination mechanisms become **saturated**, typically at very high doses (e.g., phenytoin, ethanol, aspirin at high doses). *A constant amount is eliminated in unit time.* - This describes **zero-order kinetics**, where the elimination process is saturated, and the body eliminates a fixed amount of drug per unit of time, regardless of the plasma concentration. - In **first-order kinetics**, a **constant *fraction*** (not amount) is eliminated per unit time.

Enzymes Indian Medical PG Question 8: Acetyl CoA carboxylase is stimulated by all except which of the following?

• A. Acyl CoA (Correct Answer)
• B. ATP
• C. Insulin
• D. Citrate

Enzymes Explanation: ***Acyl CoA*** - **Acyl CoA** (specifically long-chain fatty acyl CoAs) is an **inhibitor** of acetyl CoA carboxylase (ACC), signifying an abundance of fatty acids and a need to reduce further synthesis. - This feedback inhibition helps regulate **fatty acid synthesis**, ensuring that the pathway is downregulated when sufficient fatty acids are present. *Citrate* - **Citrate** is a potent **allosteric activator** of acetyl CoA carboxylase, indicating a high energy state and excess mitochondrial acetyl CoA, which can be channeled into fatty acid synthesis. - Its presence promotes the polymerization of ACC monomers into active polymers, enhancing enzyme activity. *ATP* - **ATP** is required as a substrate for the carboxylation reaction catalyzed by ACC, providing the energy for the formation of **malonyl CoA**. - High levels of ATP indirectly signal a state of energy abundance, which favors anabolic processes like fatty acid synthesis. *Insulin* - **Insulin** is a hormonal activator of acetyl CoA carboxylase, promoting its dephosphorylation via **protein phosphatase 2A**. - This dephosphorylation leads to increased enzyme activity, stimulating **fatty acid synthesis** in response to high blood glucose after a meal.

Enzymes Indian Medical PG Question 9: Which amino acid can be utilized in both gluconeogenesis and ketogenesis?

• A. Leucine
• B. Valine
• C. Arginine
• D. Tyrosine (Correct Answer)

Enzymes Explanation: ***Tyrosine (Correct Answer)*** - Tyrosine is **both glucogenic and ketogenic**, making it the correct answer. - It is **glucogenic** because its metabolism yields **fumarate**, which can enter the TCA cycle and contribute to **gluconeogenesis**. - It is also **ketogenic** because its degradation produces **acetoacetate**, a **ketone body**. *Leucine* - Leucine is a purely **ketogenic** amino acid, meaning its catabolism only produces **acetyl-CoA** and **acetoacetate**. - It cannot be converted into glucose precursors and therefore does not contribute to gluconeogenesis. *Valine* - Valine is a purely **glucogenic** amino acid, meaning its metabolism produces **succinyl-CoA**. - Succinyl-CoA can be converted into **oxaloacetate** and then to glucose via gluconeogenesis, but it does not produce ketone bodies. *Arginine* - Arginine is a purely **glucogenic** amino acid, serving as a precursor for **α-ketoglutarate** in the TCA cycle. - This pathway allows its carbon skeleton to be diverted into glucose production, but it does not yield ketone bodies.

Enzymes Indian Medical PG Question 10: In glycolysis, which of the following enzymes is not involved?

• A. Pyruvate dehydrogenase (Correct Answer)
• B. Phosphofructokinase
• C. Glucokinase
• D. Pyruvate kinase

Enzymes Explanation: ***Pyruvate dehydrogenase*** - **Pyruvate dehydrogenase** is a mitochondrial enzyme complex that converts **pyruvate** to **acetyl-CoA** in the link reaction, which occurs after glycolysis and prepares for the citric acid cycle. - It is not directly involved in the ten-step glycolytic pathway itself, which converts glucose to pyruvate. *Phosphofructokinase* - **Phosphofructokinase-1 (PFK-1)** is a key regulatory enzyme in glycolysis, catalyzing the phosphorylation of **fructose-6-phosphate** to **fructose-1,6-bisphosphate**. - This step is often considered the **rate-limiting step** of glycolysis. *Glucokinase* - **Glucokinase**, located primarily in the liver and pancreatic beta cells, phosphorylates glucose to **glucose-6-phosphate** in the first step of glycolysis. - It has a high **Km** (low affinity) for glucose, allowing it to respond to high glucose concentrations. *Pyruvate kinase* - **Pyruvate kinase** catalyzes the final step of glycolysis, transferring a phosphate group from **phosphoenolpyruvate (PEP)** to ADP to form **ATP** and **pyruvate**. - This is one of the **irreversible** steps in glycolysis and a point of regulation.

Enzymes Flashcard 1 of 10

Question: The catalytic efficiency of an enzyme is expressed as the ratio of _____

Answer: Kcat/Km.

Enzymes Flashcard 2 of 10

Question: Glycogen synthase belongs to the _____ group of enzymes.

Answer: transferase

Enzymes Flashcard 3 of 10

Question: Which enzymes catalyze the cleavage of C-C, C-O, C-N, and other covalent bonds by atom elimination, thereby generating double bonds?_____

Answer: Lyases

Enzymes Flashcard 4 of 10

Question: _____ is an obligate activator of pyruvate carboxylase

Answer: Acetyl-CoA

Enzymes Flashcard 5 of 10

Question: Isocitrate dehydrogenase is regulated via negative feedback by _____ and NADH

Answer: ATP

Enzymes Flashcard 6 of 10

Question: Elevated _____ is the most common abnormal liver function test (LFT) in pyogenic liver abscess.

Answer: serum alkaline phosphatase (ALP) level (enzyme)

Enzymes Flashcard 7 of 10

Question: Sigmoid-shaped graph which is a property of _____ enzymes

Answer: multimeric

Enzymes Flashcard 8 of 10

Question: lead inhibits _____ and _____ enzymes

Answer: ALA dehydratase

Extra Information: 

Enzymes Flashcard 9 of 10

Question: Dihydrofolate may be converted to _____ via the enzyme dihydrofolate reductase

Answer: tetrahydrofolate

Enzymes Flashcard 10 of 10

Question: Ethanol may be converted to _____ via the enzyme alcohol dehydrogenase

Answer: acetaldehyde