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 Flashcard 1 of 5

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

Answer: Kcat/Km.

Enzymes Flashcard 2 of 5

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

Answer: transferase

Enzymes Flashcard 3 of 5

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 5

Question: _____ is an obligate activator of pyruvate carboxylase

Answer: Acetyl-CoA

Enzymes Flashcard 5 of 5

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

Answer: ATP