B.Pharm. Bachelor of Pharmacy Bachelor of Pharmacy (B.Pharm.) Biochemistry 5 — Questions and Answers
Question 1: Which amino acid is the primary precursor for gluconeogenesis released from skeletal muscle during fasting?
- Leucine
- Lysine
- Alanine (Correct answer)
- Phenylalanine
Correct answer: Alanine
Alanine carries amino groups from muscle to the liver via the glucose-alanine cycle and serves as a key gluconeogenic precursor during fasting.
Question 2: What is the function of signal peptides on newly synthesized proteins destined for the endoplasmic reticulum?
- They target the protein for proteasomal degradation
- They direct the ribosome-protein complex to the ER membrane for co-translational insertion (Correct answer)
- They activate mRNA translation in the cytosol
- They label the protein for glycosylation in the Golgi
Correct answer: They direct the ribosome-protein complex to the ER membrane for co-translational insertion
Signal peptides (N-terminal hydrophobic sequences) are recognized by the signal recognition particle (SRP), which docks the ribosome on the ER membrane.
Question 3: Glucagon stimulates glycogen breakdown in the liver primarily by activating which cascade?
- Adenylyl cyclase → cAMP → PKA → phosphorylase kinase → glycogen phosphorylase (Correct answer)
- PI3K → Akt → mTOR → glycogen synthase inhibition
- PLC → IP3 → Ca2+ → calmodulin → phosphodiesterase
- JAK → STAT → glycogenolysis gene transcription
Correct answer: Adenylyl cyclase → cAMP → PKA → phosphorylase kinase → glycogen phosphorylase
Glucagon binds its GPCR, activating adenylyl cyclase to raise cAMP, which activates PKA; PKA phosphorylates and activates glycogen phosphorylase via phosphorylase kinase.
Question 4: Which of the following statements about enzyme active sites is correct?
- They are composed exclusively of hydrophobic amino acid residues
- They are rigid and do not change shape upon substrate binding
- They are complementary in shape and charge to the transition state of the reaction (Correct answer)
- They bind the product more tightly than the substrate to enhance catalysis
Correct answer: They are complementary in shape and charge to the transition state of the reaction
Enzymes are best complementary to the transition state (not the substrate or product), which lowers the activation energy and stabilizes the highest-energy intermediate.
Question 5: Biotin-dependent carboxylase reactions share which mechanistic feature?
- They transfer an acetyl group using CoA
- They use ATP to fix CO2 onto a biotin-enzyme intermediate before transferring it to substrate (Correct answer)
- They reduce a carbonyl using NADPH
- They phosphorylate a hydroxyl group using GTP
Correct answer: They use ATP to fix CO2 onto a biotin-enzyme intermediate before transferring it to substrate
Biotin carboxylases use ATP to carboxylate the biotin cofactor, forming carboxybiotin, which then transfers the carboxyl group to the acceptor substrate.
Question 6: Which Km-related characteristic distinguishes hexokinase (brain/muscle) from glucokinase (liver/pancreatic β-cells)?
- Hexokinase has a high Km for glucose; glucokinase has a low Km
- Hexokinase has a low Km and is saturated at normal blood glucose; glucokinase has a high Km and acts as a glucose sensor (Correct answer)
- Both enzymes have identical Km values but differ in Vmax
- Glucokinase is inhibited by glucose-6-phosphate; hexokinase is not
Correct answer: Hexokinase has a low Km and is saturated at normal blood glucose; glucokinase has a high Km and acts as a glucose sensor
Hexokinase's low Km (~0.1 mM) keeps it saturated at normal glucose, while glucokinase's high Km (~10 mM) lets it respond proportionally to rising postprandial glucose, acting as a glucose sensor.
Question 7: During the citric acid cycle, which step directly produces GTP (or ATP) by substrate-level phosphorylation?
- Isocitrate → α-ketoglutarate
- Succinyl-CoA → succinate (Correct answer)
- Succinate → fumarate
- Malate → oxaloacetate
Correct answer: Succinyl-CoA → succinate
Succinyl-CoA synthetase converts succinyl-CoA to succinate with concomitant phosphorylation of GDP to GTP (equivalent to ATP) via substrate-level phosphorylation.
B.Pharm. Bachelor of Pharmacy Bachelor of Pharmacy (B.Pharm.) Biochemistry 5
Which amino acid is the primary precursor for gluconeogenesis released from skeletal muscle during fasting?