CHAPTER LIST
,TABLE OF CONTENT
Chapter 1: Fuel Metabolism and Nutrition — Basic Principles
Chapter 2: Basic Aspects of Biochemistry — Organic Chemistry, Acid–
Base Chemistry, Amino Acids, Protein Structure and Function, and
Enzyme Kinetics
Chapter 3: Genome Maintenance (Replication), Gene Expression
(Transcription), Protein Synthesis (Translation), and Regulation of
Gene Expression
Chapter 4: Cell Biology, Signal Transduction, and the Molecular
Biology of Cancer
Chapter 5: Generation of ATP From Metabolic Fuels and Oxygen
Toxicity
Chapter 6: Carbohydrate Metabolism
Chapter 7: Lipid and Ethanol Metabolism
Chapter 8: Tissue Metabolism — Nitrogen-Containing Nutrient
Absorption and Digestion, and Pathologies of Nitrogen Metabolism
Chapter 9: Human Genetics — An Introduction
,Chapter 1
Fuel Metabolism & Nutrition — Basic Principles
1. A 24-year-old man eats a carbohydrate-rich meal. Which immediate
biochemical event in hepatocytes most directly reduces hepatic glucose output
during the fed state?
A. Activation of hormone-sensitive lipase (HSL)
B. Increased phosphorylation (activation) of phosphofructokinase-2 (PFK-2) to
raise fructose-2,6-bisphosphate
C. Increased cAMP levels activating protein kinase A (PKA)
D. Upregulation of PEP carboxykinase (PEPCK) expression
Answer: B
Rationale: In the fed state insulin:glucagon ratio is high. Insulin activates
phosphoprotein phosphatases which shift PFK-2/FBPase-2 toward the kinase
state, increasing fructose-2,6-bisphosphate (F2,6BP). F2,6BP is a potent
activator of PFK-1 (glycolysis) and inhibitor of fructose-1,6-bisphosphatase
(gluconeogenesis), thereby decreasing hepatic glucose output. Activation of HSL
(A) occurs in adipose during fasting; increased cAMP/PKA (C) occurs with
glucagon/epinephrine (fasting); upregulation of PEPCK (D) is a slower
transcriptional response in gluconeogenesis.
Key words: fed state, insulin, PFK-2, fructose-2,6-bisphosphate,
gluconeogenesis inhibition
2. Which tissue is the primary site for ketone body synthesis and why?
A. Skeletal muscle — due to abundant mitochondria and high fatty-acid
oxidation
B. Liver — because hepatocytes express HMG-CoA lyase and lack acetoacetate-
utilizing thiophorase (SCOT)
C. Adipose tissue — because adipocytes produce large amounts of acetyl-CoA
for export
D. Brain — because neurons can convert fatty acids to ketones during fasting
Answer: B
Rationale: Ketogenesis occurs predominantly in liver mitochondria because
hepatocytes have the enzymes for converting acetyl-CoA → HMG-CoA →
,acetoacetate/β-hydroxybutyrate (HMG-CoA lyase present) and lack succinyl-
CoA:acetoacetate CoA-transferase (SCOT/thiophorase) required to use ketones
— thus liver produces but cannot utilize ketones. Skeletal muscle (A) uses
ketones but is not the main producer. Adipose (C) releases fatty acids, but
lacks the enzymatic machinery for ketogenesis. Brain (D) cannot oxidize fatty
acids to ketones.
Key words: ketogenesis, liver, HMG-CoA lyase, SCOT, acetoacetate, β-
hydroxybutyrate
3. A patient with uncontrolled type 1 diabetes presents with hyperglycemia and
ketonemia. Mechanistically, which change most directly causes increased
hepatic ketone production?
A. Increased insulin → increased glucose uptake by adipose
B. Increased glucagon → increased hormone-sensitive lipase activity in adipose
C. Decreased lipolysis due to high insulin
D. Inhibition of hepatic fatty-acid transport into mitochondria
Answer: B
Rationale: In type 1 diabetes insulin deficiency causes a relative increase in
glucagon. Glucagon (and low insulin) increases HSL activity in adipose →
increased lipolysis → elevated plasma free fatty acids (FFAs) transported to the
liver. Hepatic β-oxidation of FFAs produces excess acetyl-CoA, overwhelming
TCA capacity and favoring ketogenesis. Increased insulin (A) would do the
opposite. Decreased lipolysis (C) is wrong. Inhibition of FA mitochondrial
transport (D) would decrease β-oxidation and ketogenesis.
Key words: type 1 diabetes, glucagon, HSL, lipolysis, free fatty acids,
ketogenesis
4. During a prolonged fast, which of the following correctly describes hepatic
glucose production sources over time?
A. Glycogenolysis predominates after several days; gluconeogenesis
predominant in first 12–24 hours
B. Glycogen stores maintain blood glucose for ~24 hours, then gluconeogenesis
predominates for prolonged fasting
C. Gluconeogenesis is negligible in early fasting because proteins cannot be
used for glucose synthesis
D. Ketones replace gluconeogenesis as the sole source of glucose after 48 hours
Answer: B
,Rationale: In fasting, hepatic glycogenolysis maintains blood glucose for about
12–24 hours (often up to ~24 hours). After glycogen is depleted,
gluconeogenesis (from lactate, glycerol, and amino acids) becomes the primary
source of blood glucose. Gluconeogenesis increases over prolonged fasting; it is
not negligible early (C). Ketones do not produce glucose—rather they spare
glucose use by peripheral tissues; they do not replace gluconeogenesis as a
glucose source (D).
Key words: fasting, glycogenolysis, gluconeogenesis, time course, glycogen
depletion
5. A 35-year-old obese patient has high fasting insulin and increased de novo
lipogenesis in the liver. Which of the following molecular signals best explains
insulin’s stimulation of lipogenesis?
A. Activation of AMP-activated protein kinase (AMPK) → phosphorylation
(activation) of acetyl-CoA carboxylase (ACC)
B. Sterol regulatory element-binding protein-1c (SREBP-1c) induction of
lipogenic enzymes
C. Glucagon receptor signaling increasing cAMP and PKA activity
D. Increased CPT-1 activity promoting fatty-acid oxidation
Answer: B
Rationale: Insulin stimulates lipogenesis in the liver by activating
transcription factors such as SREBP-1c and carbohydrate-response element
binding protein (ChREBP) that increase expression of lipogenic enzymes (e.g.,
ACC, fatty acid synthase). AMPK activation (A) inhibits ACC and lipogenesis
(opposite). Glucagon/PKA signaling (C) promotes catabolism. Increased CPT-1
(D) promotes FA oxidation, not lipogenesis.
Key words: insulin, lipogenesis, SREBP-1c, ACC, fatty acid synthase, de novo
lipogenesis
6. Which regulator ensures that glycolysis and gluconeogenesis are not highly
active simultaneously in the liver?
A. Reciprocal allosteric regulation of PFK-1 and F1,6BPase by fructose-2,6-
bisphosphate
B. Both pathways share the same irreversible enzymes so they cannot operate
together
C. Glucokinase directly inhibits PEP carboxykinase (PEPCK) activity
D. Hexokinase and glucokinase are allosteric inhibitors of pyruvate carboxylase
, Answer: A
Rationale: The key reciprocal regulator is fructose-2,6-bisphosphate (F2,6BP):
it activates PFK-1 (glycolysis) and inhibits fructose-1,6-bisphosphatase
(gluconeogenesis), preventing futile cycling. Although pathways share some
reversible enzymes, they also have different irreversible steps with unique
enzymes (B is false). Glucokinase (C) does not directly inhibit PEPCK.
Hexokinase/glucokinase are not allosteric inhibitors of pyruvate carboxylase
(D).
Key words: metabolic regulation, F2,6BP, PFK-1, F1,6BPase, futile cycling
7. A researcher measures the RQ (respiratory quotient) of a subject and obtains
a value close to 1.0. Which metabolic state and substrate use best explain that
RQ?
A. Starvation — predominant fatty-acid oxidation
B. Post-absorptive fasting — mixed substrate oxidation
C. Immediately postprandial after a carbohydrate meal — primarily
carbohydrate oxidation
D. Ketogenic diet — predominant ketone oxidation
Answer: C
Rationale: RQ = CO₂ produced / O₂ consumed. Pure carbohydrate oxidation
yields RQ ≈ 1.0; fat oxidation gives RQ ≈ 0.7; protein is ~0.8. An RQ close to 1.0
indicates predominant carbohydrate oxidation, which occurs postprandially
after a carbohydrate meal. Starvation or fatty-acid oxidation would lower RQ
(~0.7).
Key words: RQ, respiratory quotient, carbohydrate oxidation, postprandial
8. Which enzyme is rate limiting for fatty-acid entry into the mitochondrial
matrix for β-oxidation, and how is it regulated by malonyl-CoA?
A. Carnitine palmitoyltransferase-1 (CPT-1) — inhibited by malonyl-CoA
B. Acyl-CoA dehydrogenase — activated by malonyl-CoA
C. Carnitine acyltransferase II (CPT-2) — activated by malonyl-CoA
D. Hormone-sensitive lipase — inhibited by malonyl-CoA
Answer: A
Rationale: CPT-1 catalyzes transfer of long-chain acyl groups from CoA to
carnitine for transport into mitochondria and is the rate-limiting step for
,TABLE OF CONTENT
Chapter 1: Fuel Metabolism and Nutrition — Basic Principles
Chapter 2: Basic Aspects of Biochemistry — Organic Chemistry, Acid–
Base Chemistry, Amino Acids, Protein Structure and Function, and
Enzyme Kinetics
Chapter 3: Genome Maintenance (Replication), Gene Expression
(Transcription), Protein Synthesis (Translation), and Regulation of
Gene Expression
Chapter 4: Cell Biology, Signal Transduction, and the Molecular
Biology of Cancer
Chapter 5: Generation of ATP From Metabolic Fuels and Oxygen
Toxicity
Chapter 6: Carbohydrate Metabolism
Chapter 7: Lipid and Ethanol Metabolism
Chapter 8: Tissue Metabolism — Nitrogen-Containing Nutrient
Absorption and Digestion, and Pathologies of Nitrogen Metabolism
Chapter 9: Human Genetics — An Introduction
,Chapter 1
Fuel Metabolism & Nutrition — Basic Principles
1. A 24-year-old man eats a carbohydrate-rich meal. Which immediate
biochemical event in hepatocytes most directly reduces hepatic glucose output
during the fed state?
A. Activation of hormone-sensitive lipase (HSL)
B. Increased phosphorylation (activation) of phosphofructokinase-2 (PFK-2) to
raise fructose-2,6-bisphosphate
C. Increased cAMP levels activating protein kinase A (PKA)
D. Upregulation of PEP carboxykinase (PEPCK) expression
Answer: B
Rationale: In the fed state insulin:glucagon ratio is high. Insulin activates
phosphoprotein phosphatases which shift PFK-2/FBPase-2 toward the kinase
state, increasing fructose-2,6-bisphosphate (F2,6BP). F2,6BP is a potent
activator of PFK-1 (glycolysis) and inhibitor of fructose-1,6-bisphosphatase
(gluconeogenesis), thereby decreasing hepatic glucose output. Activation of HSL
(A) occurs in adipose during fasting; increased cAMP/PKA (C) occurs with
glucagon/epinephrine (fasting); upregulation of PEPCK (D) is a slower
transcriptional response in gluconeogenesis.
Key words: fed state, insulin, PFK-2, fructose-2,6-bisphosphate,
gluconeogenesis inhibition
2. Which tissue is the primary site for ketone body synthesis and why?
A. Skeletal muscle — due to abundant mitochondria and high fatty-acid
oxidation
B. Liver — because hepatocytes express HMG-CoA lyase and lack acetoacetate-
utilizing thiophorase (SCOT)
C. Adipose tissue — because adipocytes produce large amounts of acetyl-CoA
for export
D. Brain — because neurons can convert fatty acids to ketones during fasting
Answer: B
Rationale: Ketogenesis occurs predominantly in liver mitochondria because
hepatocytes have the enzymes for converting acetyl-CoA → HMG-CoA →
,acetoacetate/β-hydroxybutyrate (HMG-CoA lyase present) and lack succinyl-
CoA:acetoacetate CoA-transferase (SCOT/thiophorase) required to use ketones
— thus liver produces but cannot utilize ketones. Skeletal muscle (A) uses
ketones but is not the main producer. Adipose (C) releases fatty acids, but
lacks the enzymatic machinery for ketogenesis. Brain (D) cannot oxidize fatty
acids to ketones.
Key words: ketogenesis, liver, HMG-CoA lyase, SCOT, acetoacetate, β-
hydroxybutyrate
3. A patient with uncontrolled type 1 diabetes presents with hyperglycemia and
ketonemia. Mechanistically, which change most directly causes increased
hepatic ketone production?
A. Increased insulin → increased glucose uptake by adipose
B. Increased glucagon → increased hormone-sensitive lipase activity in adipose
C. Decreased lipolysis due to high insulin
D. Inhibition of hepatic fatty-acid transport into mitochondria
Answer: B
Rationale: In type 1 diabetes insulin deficiency causes a relative increase in
glucagon. Glucagon (and low insulin) increases HSL activity in adipose →
increased lipolysis → elevated plasma free fatty acids (FFAs) transported to the
liver. Hepatic β-oxidation of FFAs produces excess acetyl-CoA, overwhelming
TCA capacity and favoring ketogenesis. Increased insulin (A) would do the
opposite. Decreased lipolysis (C) is wrong. Inhibition of FA mitochondrial
transport (D) would decrease β-oxidation and ketogenesis.
Key words: type 1 diabetes, glucagon, HSL, lipolysis, free fatty acids,
ketogenesis
4. During a prolonged fast, which of the following correctly describes hepatic
glucose production sources over time?
A. Glycogenolysis predominates after several days; gluconeogenesis
predominant in first 12–24 hours
B. Glycogen stores maintain blood glucose for ~24 hours, then gluconeogenesis
predominates for prolonged fasting
C. Gluconeogenesis is negligible in early fasting because proteins cannot be
used for glucose synthesis
D. Ketones replace gluconeogenesis as the sole source of glucose after 48 hours
Answer: B
,Rationale: In fasting, hepatic glycogenolysis maintains blood glucose for about
12–24 hours (often up to ~24 hours). After glycogen is depleted,
gluconeogenesis (from lactate, glycerol, and amino acids) becomes the primary
source of blood glucose. Gluconeogenesis increases over prolonged fasting; it is
not negligible early (C). Ketones do not produce glucose—rather they spare
glucose use by peripheral tissues; they do not replace gluconeogenesis as a
glucose source (D).
Key words: fasting, glycogenolysis, gluconeogenesis, time course, glycogen
depletion
5. A 35-year-old obese patient has high fasting insulin and increased de novo
lipogenesis in the liver. Which of the following molecular signals best explains
insulin’s stimulation of lipogenesis?
A. Activation of AMP-activated protein kinase (AMPK) → phosphorylation
(activation) of acetyl-CoA carboxylase (ACC)
B. Sterol regulatory element-binding protein-1c (SREBP-1c) induction of
lipogenic enzymes
C. Glucagon receptor signaling increasing cAMP and PKA activity
D. Increased CPT-1 activity promoting fatty-acid oxidation
Answer: B
Rationale: Insulin stimulates lipogenesis in the liver by activating
transcription factors such as SREBP-1c and carbohydrate-response element
binding protein (ChREBP) that increase expression of lipogenic enzymes (e.g.,
ACC, fatty acid synthase). AMPK activation (A) inhibits ACC and lipogenesis
(opposite). Glucagon/PKA signaling (C) promotes catabolism. Increased CPT-1
(D) promotes FA oxidation, not lipogenesis.
Key words: insulin, lipogenesis, SREBP-1c, ACC, fatty acid synthase, de novo
lipogenesis
6. Which regulator ensures that glycolysis and gluconeogenesis are not highly
active simultaneously in the liver?
A. Reciprocal allosteric regulation of PFK-1 and F1,6BPase by fructose-2,6-
bisphosphate
B. Both pathways share the same irreversible enzymes so they cannot operate
together
C. Glucokinase directly inhibits PEP carboxykinase (PEPCK) activity
D. Hexokinase and glucokinase are allosteric inhibitors of pyruvate carboxylase
, Answer: A
Rationale: The key reciprocal regulator is fructose-2,6-bisphosphate (F2,6BP):
it activates PFK-1 (glycolysis) and inhibits fructose-1,6-bisphosphatase
(gluconeogenesis), preventing futile cycling. Although pathways share some
reversible enzymes, they also have different irreversible steps with unique
enzymes (B is false). Glucokinase (C) does not directly inhibit PEPCK.
Hexokinase/glucokinase are not allosteric inhibitors of pyruvate carboxylase
(D).
Key words: metabolic regulation, F2,6BP, PFK-1, F1,6BPase, futile cycling
7. A researcher measures the RQ (respiratory quotient) of a subject and obtains
a value close to 1.0. Which metabolic state and substrate use best explain that
RQ?
A. Starvation — predominant fatty-acid oxidation
B. Post-absorptive fasting — mixed substrate oxidation
C. Immediately postprandial after a carbohydrate meal — primarily
carbohydrate oxidation
D. Ketogenic diet — predominant ketone oxidation
Answer: C
Rationale: RQ = CO₂ produced / O₂ consumed. Pure carbohydrate oxidation
yields RQ ≈ 1.0; fat oxidation gives RQ ≈ 0.7; protein is ~0.8. An RQ close to 1.0
indicates predominant carbohydrate oxidation, which occurs postprandially
after a carbohydrate meal. Starvation or fatty-acid oxidation would lower RQ
(~0.7).
Key words: RQ, respiratory quotient, carbohydrate oxidation, postprandial
8. Which enzyme is rate limiting for fatty-acid entry into the mitochondrial
matrix for β-oxidation, and how is it regulated by malonyl-CoA?
A. Carnitine palmitoyltransferase-1 (CPT-1) — inhibited by malonyl-CoA
B. Acyl-CoA dehydrogenase — activated by malonyl-CoA
C. Carnitine acyltransferase II (CPT-2) — activated by malonyl-CoA
D. Hormone-sensitive lipase — inhibited by malonyl-CoA
Answer: A
Rationale: CPT-1 catalyzes transfer of long-chain acyl groups from CoA to
carnitine for transport into mitochondria and is the rate-limiting step for
