Biochem 44 Flashcards


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1

Loss of which liver-resident immune cell most directly explains impaired early antitumor defense?
A. Kupffer macrophages
B. Pit NK cells
C. Ito stellate cells
D. Cholangiocytes

B. Pit NK cells

2

A new anticonvulsant is primarily metabolized by cytochrome P450. Where are these enzymes classically located?
A. Smooth ER
B. Rough ER
C. Cytosol
D. Mitochondrial matrix

A. Smooth ER

3

After taking a lipophilic drug, the first metabolic step exposes a hydroxyl group to enable later conjugation. Which detoxification phase is this?
A. Phase II
B. Biliary secretion
C. Renal filtration
D. Phase I

D. Phase I

4

A xenobiotic is made more water-soluble by addition of glycine, sulfate, or glucuronic acid. Which detoxification phase best fits?
A. Phase I
B. Beta oxidation
C. Phase II
D. Urea synthesis

C. Phase II

5

A patient on a statin drinks grapefruit juice daily and develops myalgias with elevated CK and transaminases. What mechanism best explains toxicity?
A. CYP2E1 inhibition
B. Decreased gut absorption
C. Increased renal clearance
D. CYP3A4 inhibition

D. CYP3A4 inhibition

6

During cytochrome P450 detoxification, which reactive intermediate classically forms and can contribute to tissue injury?
A. Carbocation
B. Free radical
C. Nitrate
D. Disaccharide

B. Free radical

7

A plastics factory worker exposed to vinyl chloride forms chloroethylene oxide via a Phase I reaction. Which enzyme most directly catalyzes this activation?
A. CYP2E1
B. CYP3A4
C. CYP1A2
D. CYP2C9

A. CYP2E1

8

Vinyl chloride can be converted to chloroacetaldehyde, then safely eliminated after conjugation with which molecule?
A. Sulfate
B. Glycine
C. Reduced glutathione
D. Glucuronic acid

C. Reduced glutathione

9

Chloroethylene oxide contributes to carcinogenesis by forming adducts with which DNA base?
A. Cytosine
B. Guanine
C. Adenine
D. Thymine

B. Guanine

10

Long-term vinyl chloride exposure is most classically associated with which hepatic malignancy?
A. Hepatoblastoma
B. Cholangiocarcinoma
C. Hepatocellular carcinoma
D. Hepatic angiosarcoma

D. Hepatic angiosarcoma

11

A patient eats mold-contaminated stored peanuts and later develops hepatocellular carcinoma risk from aflatoxin exposure. Which organism produced the toxin?
A. Aspergillus flavus
B. Candida albicans
C. Histoplasma capsulatum
D. Penicillium chrysogenum

A. Aspergillus flavus

12

Aflatoxin B1 promotes hepatocarcinogenesis most directly through a G→T mutation in which gene?
A. RB1
B. APC
C. p53
D. BRCA1

C. p53

13

Bioactivation of aflatoxin B1 to its 8,9-epoxide form is most directly mediated by which enzyme?
A. CYP2E1
B. CYP3A4
C. CYP2A1
D. CYP1A2

C. CYP2A1

14

The 8,9-epoxide of aflatoxin B1 forms covalent DNA adducts predominantly with which base?
A. Thymine
B. Guanine
C. Cytosine
D. Adenine

B. Guanine

15

In addition to DNA damage, aflatoxin B1 epoxide can bind proteins by reacting with which amino acid residue?
A. Serine
B. Histidine
C. Cysteine
D. Lysine

D. Lysine

16

A patient takes therapeutic-dose acetaminophen. Its reactive metabolite is rendered safe for urinary excretion primarily by conjugation with:
A. Glutathione
B. Sulfate
C. Glycine
D. Glucuronic acid

A. Glutathione

17

After a massive acetaminophen ingestion, which pathways are overwhelmed, increasing formation of the toxic metabolite?
A. Ketogenesis and lipolysis
B. Urea cycle enzymes
C. Bile salt transport
D. Sulfation and glucuronidation

D. Sulfation and glucuronidation

18

A patient with acetaminophen overdose develops hepatocyte necrosis due to an unstable metabolite. Which metabolite is responsible?
A. Acetyl-CoA
B. Acetylaldehyde
C. NAPQI
D. Urobilinogen

C. NAPQI

19

The enzyme that produces NAPQI and is inducible by alcohol is:
A. CYP2E1
B. CYP2A1
C. CYP3A4
D. UGT1A1

A. CYP2E1

20

A chronic alcohol user develops severe acetaminophen toxicity after a dose that was previously tolerated. The best explanation is:
A. Lower portal blood flow
B. More CYP2E1 activity
C. Less NAPQI formation
D. Faster renal clearance

B. More CYP2E1 activity

21

A patient has high dietary cholesterol intake with efficient intestinal absorption. What hepatic compensation is most expected?
A. Increases cholesterol synthesis
B. Decreases cholesterol export
C. Decreases cholesterol synthesis
D. Increases ketone production

C. Decreases hepatic synthesis

22

A patient with liver failure develops hyperammonemia. Which organ is primarily responsible for synthesizing urea under normal conditions?
A. Kidney cortex
B. Skeletal muscle
C. Small intestine
D. Liver

D. Liver

23

Most nitrogen destined for hepatic urea synthesis arrives primarily carried on which molecules?
A. Lactate and pyruvate
B. Glutamine and alanine
C. Leucine and lysine
D. Serine and proline

B. Glutamine and alanine

24

Most protein entering the GI tract is metabolized by bacteria, releasing which species that enters the portal vein?
A. Ammonium ion
B. Urea
C. Nitrate
D. CO2

A. Ammonium ion

25

What mechanism most directly explains hepatic encephalopathy here?
A. Bilirubin blocks synapses
B. Hypoglycemia causes seizures
C. Systemic ammonium reaches brain
D. Lactate causes brain acidosis

C. Systemic ammonium reaches brain

26

In hepatic ethanol metabolism, the principal cytochrome P450 enzyme oxidizing ethanol to acetylaldehyde is:
A. CYP1A2
B. CYP2C9
C. CYP3A4
D. CYP2E1

D. CYP2E1

27

The term “microsomal enzymes” most directly refers to:
A. Smooth ER P450s
B. Mitochondrial oxidases
C. Lysosomal hydrolases
D. Cytosolic kinases

A. Smooth ER P450s

28

Sialic acid found on serum proteins is also known as:
A. N-acetylmuramic acid
B. N-acetylneuraminic acid
C. N-acetylglucosamine
D. N-acetylgalactosamine

B. N-acetylneuraminic acid

29

Sialic acid (NANA) made by the liver is best characterized as which surface feature of serum proteins?
A. N-linked oligosaccharide
B. Lipid anchor
C. Phosphorylated tag
D. O-linked sugar

D. O-linked sugar

30

If statins are taken regularly with grapefruit juice, statin levels may rise approximately:
A. 2-fold
B. 5-fold
C. 15-fold
D. 50-fold

C. 15-fold

31

The key functional outcome of Phase II reactions is best summarized as:
A. Adds negative charged group
B. Removes reactive oxygen species
C. Cleaves peptide bonds
D. Generates acetyl-CoA

A. Adds negative charged group

32

A patient with impaired liver innate immunity is unusually susceptible to hepatic viral invasion. Which cell type normally provides liver-specific NK defense?
A. Kupffer macrophages
B. Pit NK cells
C. Ito stellate cells
D. Endothelial cells

B. Pit NK cells

33

A patient with reduced hepatic clearance has prolonged half-life of an “aged” serum glycoprotein. Which change normally flags serum proteins for removal and degradation?
A. Added fucose residues
B. Loss of NANA residues
C. Added phosphate residues
D. Increased disulfide bonding

B. Loss of NANA residues

34

A transfusion service develops a test for oxidative stress tolerance in RBCs. Which pathway’s major function best supports this defense by generating NADPH and 5-carbon sugars?
A. Glycolysis
B. TCA cycle
C. Beta oxidation
D. Pentose phosphate pathway

D. Pentose phosphate pathway

35

NADPH is most critical for maintaining activity of which enzyme?
A. Glutathione reductase
B. Glutathione peroxidase
C. Superoxide dismutase
D. Catalase

A. Glutathione reductase

36

In severe oxidative stress, oxidized glutathione accumulates. Which reaction is directly catalyzed by glutathione reductase?
A. GSH → GSSG
B. NADP+ → NADPH
C. GSSG → GSH
D. H2O2 → H2O

C. GSSG → GSH

37

A patient has markedly decreased glutathione reductase activity. Loss of which protection is most direct?
A. Ketone body utilization
B. Free radical injury defense
C. Bile acid conjugation
D. Urea cycle function

B. Free radical injury defense

38

Which pathway is required in all cells for ribose generation, especially rapidly dividing cells?
A. Pentose phosphate pathway
B. Cori cycle
C. Malate-aspartate shuttle
D. Carnitine shuttle

A. Pentose phosphate pathway

39

After a high-carbohydrate meal, hepatic glucose uptake increases sharply. This dependence on high portal glucose is best explained by which shared property?
A. Low Km for both proteins
B. Insulin-independent nuclear transport
C. Constitutive mitochondrial localization
D. High Km for both proteins

D. High Km for both proteins

40

A fasting hepatocyte shows reduced cytosolic glucokinase activity. In the absence of glucose, glucokinase is partially sequestered where and bound to what?
A. Cytosol; insulin receptor
B. Smooth ER; PPARα
C. Nucleus; GK regulatory protein
D. Mitochondria; CPT1

C. Nucleus; GK regulatory protein

41

A patient receives a drug that increases hepatic fructose-2,6-bisphosphate. What is the net effect on glycolysis rate?
A. Decreases markedly
B. Increases
C. No change
D. Cycles with feeding

B. Increases

42

A 48-hour fast shifts the liver’s primary fuel source. Which substrate is the major fuel for the liver during fasting?
A. Long-chain fatty acids
B. Short-chain fatty acids
C. Glucose from portal vein
D. Branched-chain amino acids

A. Long-chain fatty acids

43

A newborn has accumulation of very-long-chain fatty acids (C20–C26). These fatty acids are first activated to CoA derivatives by an enzyme located in the:
A. Mitochondrial matrix
B. Cytosolic ribosomes
C. Rough ER lumen
D. Peroxisomal membrane

D. Peroxisomal membrane

44

During fasting, hepatic gene transcription increases for fatty acid uptake and oxidation proteins. Which receptor directly regulates these genes?
A. SREBP-1c
B. LXR
C. PPAR
D. FXR

C. PPAR

45

A patient with high circulating free fatty acids shows increased transcription of fatty-acid metabolism proteins. Fatty acids act as endogenous ligands for which liver-dominant isoform?
A. PPARα
B. PPARγ
C. PPARδ
D. PPARβ

A. PPARα

46

A patient ingests benzoate-containing food preservatives. Benzoate (and salicylic acid) resemble medium-chain fatty acids and are activated to acyl-CoA derivatives by which enzyme?
A. Very-long-chain acyl-CoA synthetase
B. Medium-chain fatty acyl-CoA enzyme
C. LCAT
D. Glucokinase

B. Medium-chain fatty acyl-CoA enzyme

47

After activation, benzoate and salicylic acid are targeted for urinary excretion by conjugation with:
A. Glucuronic acid
B. Sulfate
C. Glutathione
D. Glycine

D. Glycine

48

A cirrhotic patient has elevated plasma triglycerides without major dietary change. The most direct mechanism is decreased activity of:
A. LCAT and ACAT
B. ApoA-I and CETP
C. LPL and hepatic TG lipase
D. LDL receptor and PCSK9

C. LPL and hepatic TG lipase

49

A patient with hepatocellular disease has reduced cholesterol ester formation. Decreased activity of which enzyme best explains this?
A. lecithin-cholesterol acyltransferase
B. LDL receptor and PCSK9
C. Very-long-chain acyl-CoA synthetase
D. CETP

A. lecithin-cholesterol acyltransferase

50

A toxicologist notes that multiple organs serve excretory roles with broad detoxifying mechanisms. Besides liver, which organs fit this description?
A. Lung and spleen
B. Kidney and gut
C. Brain and skin
D. Bone marrow and thymus

B. Kidney and gut

51

Approximately 75% of the liver’s blood supply normally arrives via the:
A. Hepatic artery
B. Splenic artery
C. Celiac trunk
D. Portal vein

D. Portal vein

52

Which organ’s venous blood is not a typical contributor to portal venous inflow?
A. Stomach
B. Pancreas
C. Kidney
D. Spleen

C. Kidney

53

A pathologist describes “expandable vascular channels” running through hepatic lobules. Which structure is being described?
A. Sinusoids
B. Central veins
C. Bile canaliculi
D. Portal triads

A. Sinusoids

54

Drug molecules in plasma rapidly access hepatocytes across a “leaky” barrier in hepatic lobules. Which cells line this leaky channel?
A. Hepatocytes
B. Endothelial cells
C. Stellate cells
D. Cholangiocytes

B. Endothelial cells

55

A patient with obstructive cholestasis has impaired exocrine output from the liver. What is the primary exocrine secretion?
A. Albumin
B. Urea
C. Complement proteins
D. Bile

D. Bile

56

During biliary drainage, lumina of bile ducts fuse and ultimately form the:
A. Cystic duct
B. Hepatic duct
C. Common bile duct
D. Pancreatic duct

C. Common bile duct

57

A surgeon notes a fibrous covering enveloping the entire liver surface and sending septa inward (Glisson's capsule). This covering is primarily:
A. Connective tissue capsule
B. Simple squamous epithelium
C. Smooth muscle sheath
D. Elastic cartilage plate

A. Connective tissue capsule

58

A histology slide shows the dominant cell type by volume within liver parenchyma. Which cell type composes most liver volume?
A. Kupffer cells
B. Hepatocytes
C. Cholangiocytes
D. Endothelial cells

B. Hepatocytes

59

Despite normally low turnover, which feature best explains why hepatocytes can restore liver mass?
A. Constitutive mitosis at baseline
B. Stem-cell-only regeneration
C. Stimulated growth after damage
D. Permanent post-mitotic state

C. Stimulated growth after damage

60

A patient with bacteremia has rapid clearance of microbes from portal blood. Which liver-resident cell type provides endocytotic and phagocytic capacity?
A. Stellate cells
B. Pit cells
C. Cholangiocytes
D. Kupffer cells

D. Kupffer cells

61

A lab intentionally removes terminal residues from serum glycoproteins and observes accelerated clearance from blood. Which residue’s loss triggers this clearance signal?
A. Mannose
B. Sialic acid
C. Glucose
D. Ribose

B. Sialic acid

62

A patient with low NADPH cannot maintain reduced glutathione stores. Which enzyme activity is most directly compromised by NADPH deficiency?
A. LCAT
B. MMFAE
C. Glucokinase
D. Glutathione reductase

D. Glutathione reductase

63

A lipid profile suggests selective impairment in handling very-long-chain fatty acids. Which chain length most specifically matches the peroxisome-activated group?
A. C20–C26
B. C6–C10
C. C12–C18
D. C2–C4

A. C20–C26

64

A patient takes aspirin chronically; hepatic handling of salicylic acid involves glycine conjugation. Which glycine conjugate corresponds to benzoate specifically?
A. Salicylurate
B. Glucuronate
C. Hippurate
D. Sulfate ester

C. Hippurate

65

A patient with hepatocellular disease has a lipid abnormality most directly predicted by reduced LPL and hepatic TG lipase. Which abnormality is expected?
A. Low triglycerides
B. Elevated triglycerides
C. Low LDL particles
D. Elevated cholesterol esters

B. Elevated triglycerides

66

A fed-state signal increases hepatic fructose-2,6-bisphosphate. Which pathway’s rate rises as a direct consequence?
A. Glycolysis
B. Glycogenolysis
C. Gluconeogenesis
D. Ketogenesis

A. Glycolysis

67

After a high-carb meal, glucose enters hepatocytes efficiently because hepatic uptake is tuned for high portal glucose. Which transporter best fits this “high Km” role?
A. GLUT1
B. GLUT4
C. GLUT2
D. SGLT1

C. GLUT2

68

The remaining ~25% of the liver’s blood supply is delivered by the:
A. Inferior vena cava
B. Splenic vein
C. Hepatic artery
D. Portal vein

C. Hepatic artery

69

A patient with hereditary spherocytosis has increased RBC turnover. Which liver cell type directly removes damaged erythrocytes from circulation?
A. Kupffer cells
B. Stellate cells
C. Pit cells
D. Cholangiocytes

A. Kupffer cells

70

A biopsy shows lipid-filled perisinusoidal cells with vitamin A droplets. What is the alternate name for these cells?
A. Kupffer cells
B. Ito cells
C. Pit cells
D. Endothelial cells

B. Ito cells

71

The primary hepatic storage site for vitamin A is:
A. Hepatocytes
B. Kupffer cells
C. Stellate cells
D. Bile duct cells

C. Stellate cells

72

A cirrhotic patient has progressive portal hypertension and fibrosis. Which cell type is most responsible for increased extracellular matrix synthesis in cirrhosis?
A. Hepatocytes
B. Kupffer cells
C. Pit cells
D. Stellate cells

D. Stellate cells

73

In cirrhosis, stellate cell activation most directly increases synthesis of:
A. Urea cycle enzymes
B. Extracellular matrix material
C. Bile salts
D. Albumin

B. Extracellular matrix material

74

Which cell type normally regulates sinusoidal contractility and connective tissue turnover?
A. Stellate cells
B. Kupffer cells
C. Pit cells
D. Cholangiocytes

A. Stellate cells

75

A patient with metastatic cancer shows early hepatic tumor surveillance failure. “Liver-associated lymphocytes” that mediate this defense are:
A. CD4 T cells
B. Natural killer cells
C. Plasma cells
D. Neutrophils

B. Natural killer cells

76

Hepatic “pit cells” are best classified as which immune effector type?
A. Natural killer cells
B. Dendritic cells
C. Macrophages
D. Eosinophils

A. Natural killer cells

77

A toxic compound absorbed from the gut is cleared by the liver and targeted for excretion primarily into:
A. Sweat or saliva
B. Urine or bile
C. CSF or tears
D. Lymph or sputum

B. Urine or bile

78

A clinician explains why the liver sees gut-derived toxins early after ingestion. Which concept best captures this “first access” physiology?
A. Lymphatic drainage
B. Enterohepatic circulation
C. Renal portal system
D. Coronary circulation

B. Enterohepatic circulation

79

The liver’s first access to portal blood most directly supports synthesis of which protein class?
A. Keratins
B. Myosins
C. Coagulation proteins
D. Collagens

C. Coagulation proteins

80

After a meal, the liver rapidly processes incoming substrates for nucleotide synthesis. Which products are specifically listed functions supported by first access?
A. Heme, purines, pyrimidines
B. Glycogen, lactate, ketones
C. Cholesterol, bile acids, urea
D. Creatine, carnitine, heme

A. Heme, purines, pyrimidines

81

Gut bacteria generate NH4+ that can reach the liver via portal blood. This is best categorized as a:
A. Vitamin cofactor
B. Metabolic product
C. Essential nutrient
D. Structural lipid

B. Metabolic product

82

Hepatic sinusoids allow efficient exchange with hepatocytes. Which structural feature is notably absent between endothelium and hepatocytes?
A. Tight junctions
B. Basement membrane
C. Glycocalyx
D. Fenestrations

B. Basement membrane

83

Slow portal blood flow and “leaky” endothelium most directly enhance:
A. Exchange between blood and hepatocytes
B. Myelin formation
C. Lymphocyte thymic selection
D. Bone marrow release

A. Exchange between blood and hepatocytes

84

A patient is fasting and uses amino acids for energy. Which statement best reflects hepatic metabolic flexibility?
A. Converts all amino acids to ketones
B. Converts amino acids to multiple fuels
C. Converts amino acids only to glucose
D. Cannot use aromatic amino acids

B. Converts amino acids to multiple fuels

85

The liver can convert amino acids found in proteins into:
A. Glucose, fatty acids, ketones
B. Lactate, urea, bilirubin
C. Cholesterol, bile salts, glycogen
D. Creatine, carnitine, citrate

A. Glucose, fatty acids, ketones

86

______ is created when VLDL loses triglycerides through the action of lipoprotein lipase.

IDL

87

A patient with hypertriglyceridemia has increased hepatic export of TAG. Which lipoprotein secretion delivers excess calories to adipose for TAG storage?
A. Chylomicrons
B. LDL
C. HDL
D. VLDL

D. VLDL

88

Hepatic VLDL also provides which lipid components to peripheral tissues for membrane needs?
A. Ceramides and bile acids
B. Phospholipids and cholesterol
C. Steroids and ketones
D. Glycogen and glucose

B. Phospholipids and cholesterol

89

A nuclear medicine study uses a ligand to assess receptor-mediated uptake by hepatocytes. Which receptor is used diagnostically for this purpose?
A. LDL receptor
B. Asialoglycoprotein receptor
C. Insulin receptor
D. Transferrin receptor

B. Asialoglycoprotein receptor

90

The asialoglycoprotein receptor is also known as the:
A. Hepatic binding protein
B. Kupffer receptor
C. Canalicular pump
D. Sinusoid ligand trap

A. Hepatic binding protein

91

A toxicology question defines xenobiotics. Which property best matches xenobiotics?
A. Provide caloric nutrient value
B. Stored as hepatic glycogen
C. No nutrient value
D. Required vitamin precursors

C. No nutrient value

92

The principal site for xenobiotic degradation in the body is the:
A. Kidney cortex
B. Liver
C. Skeletal muscle
D. Brain

B. Liver

93

Many xenobiotics require Phase I processing because they are:
A. Hydrophilic
B. Lipophilic
C. Polyionic
D. Protein-bound only

B. Lipophilic

94

Phase I reactions most characteristically:
A. Add negatively charged groups
B. Introduce hydroxyl reactive sites
C. Form disulfide bonds
D. Remove oxygen atoms

B. Introduce hydroxyl reactive sites

95

Conjugation reactions most characteristically add a:
A. Positively charged group
B. Negatively charged group
C. Hydrophobic ring
D. Phosphate-free radical

B. Negatively charged group

96

Which pairing best matches a Phase II conjugation group listed?
A. Glycine, sulfate, glucuronic acid
B. ATP, NADH, FADH2
C. Palmitate, stearate, oleate
D. Glucose, fructose, ribose

A. Glycine, sulfate, glucuronic acid

97

A patient has elevated steroid hormone levels due to impaired hepatic clearance. Which Phase II process is specifically used to clear steroid hormones?
A. Sulfation
B. Ureagenesis
C. Deamination
D. Ketogenesis

A. Sulfation

98

A smoker’s carcinogen contains a stable aromatic ring that humans cannot readily recycle into useful components. Which compound fits this example?
A. Benzopyrene
B. Lactate
C. Glycine
D. Citrate

A. Benzopyrene

99

Nicotine contains ring structures that are difficult to degrade. These are best described as:
A. Heterocyclic rings
B. Linear ketones
C. Saturated fatty acids
D. Simple aldehydes

A. Heterocyclic rings

100

Cytochrome P450–dependent monooxygenases are determinants in degradation of both exogenous and endogenous substances. Which is listed as an endogenous substrate class?
A. Steroids
B. Cellulose
C. Hemoglobin
D. Glycogen

A. Steroids

101

The major role of cytochrome P450 enzymes is to:
A. Reduce substrates, remove oxygen
B. Oxidize substrates, add oxygen
C. Polymerize sugars, store glycogen
D. Conjugate glycine, excrete urine

B. Oxidize substrates, add oxygen

102

A pharmacologist notes an isoform comprising ~30–40% of hepatic CYP450 and ~70% of gut-wall enterocyte CYP enzymes. Which isoform is this?
A. CYP2E1
B. CYP1A2
C. CYP3A4
D. CYP2A1

C. CYP3A4

103

A patient taking simvastatin begins a new diet including grapefruit juice daily. Which statement best explains the interaction?
A. Grapefruit induces CYP3A4
B. Grapefruit inhibits CYP3A4
C. Grapefruit inhibits CYP2E1
D. Grapefruit blocks LDL receptors

B. Grapefruit inhibits CYP3A4

104

Statin degradation most directly depends on which enzyme isoform?
A. CYP2C9
B. CYP3A4
C. CYP2D6
D. CYP1A2

B. CYP3A4

105

A patient has reduced drug metabolism specifically in gut-wall enterocytes. Which hepatic/gut CYP isoform dominates enterocytes?
A. CYP3A4
B. CYP2E1
C. CYP2A1
D. CYP2C19

A. CYP3A4

106

A patient has impaired microsomal oxidation capacity because the flavin reductase subunit can’t donate electrons. Which cofactor is required?
A. NADPH
B. NADH
C. ATP
D. FADH2

A. NADPH

107

A 52-year-old man begins a highly lipophilic medication that accumulates within hepatocyte membranes. Shortly after, his physician notes altered metabolism of several drugs processed by hepatic monooxygenases. Which structural feature of these enzymes best explains their susceptibility to modulation by membrane-partitioning drugs?

A. Integral membrane localization within smooth ER lipid bilayer
B. Free cytosolic diffusion with soluble catalytic domains
C. Nuclear chromatin binding regulating gene transcription
D. Secretion into plasma for systemic xenobiotic metabolism

A. Integral membrane localization within smooth ER lipid bilayer

108

A chronic medication accelerates its own metabolism over time. Which shared CYP feature best explains this?
A. Inducible by own substrate
B. Always constitutively expressed
C. Irreversibly inhibited by substrate
D. Active only during fasting

A. Inducible by own substrate

109

During CYP-dependent oxidation, transient reactive intermediates increase cellular injury risk. What intermediate is classically generated?
A. Disaccharide intermediate
B. Acyl-CoA intermediate
C. Nucleotide intermediate
D. Free radical intermediate

D. Free radical intermediate

110

A factory worker is exposed to vinyl chloride daily. The compound is used primarily to make:
A. Steroid hormones
B. Plastics
C. Bile acids
D. Heme intermediates

B. Plastics

111

Years later, that worker develops a rare hepatic malignancy classically linked to vinyl chloride exposure. Which tumor fits best?
A. Hepatoblastoma
B. Cholangiocarcinoma
C. Hepatic angiosarcoma
D. Hepatocellular carcinoma

C. Hepatic angiosarcoma

112

Which statement best fits?
A. CYP can bioactivate toxins
B. CYP always detoxifies toxins
C. CYP only acts in kidney
D. CYP only conjugates xenobiotics

A. CYP can bioactivate toxins

113

The CYP isoform listed as making aflatoxin B1 more toxic is:
A. CYP2E1
B. CYP1A2
C. CYP3A4
D. CYP2A1

D. CYP2A1

114

A patient taking therapeutic acetaminophen clears most of it safely via renal excretion after Phase II processing. Which pathways are listed?
A. Oxidation and reduction
B. Hydrolysis and methylation
C. Glucuronidation or sulfation
D. Deamination and transamination

C. Glucuronidation or sulfation

115

Why can acetaminophen become toxic at high doses?
A. Bile secretion stops
B. Conjugation pathways become saturated
C. Gut absorption increases
D. Renal filtration ceases

B. Conjugation pathways become saturated

116

After overdose, a CYP enzyme generates the key toxic intermediate responsible for hepatocyte injury. Which metabolite is it?
A. Biliverdin
B. Acetyl-CoA
C. Urobilinogen
D. N-acetyl-p-benzoquinoneimine

D. N-acetyl-p-benzoquinoneimine

117

NAPQI causes hepatotoxicity most directly by damaging:
A. Cellular proteins
B. Ribosomal RNA
C. Membrane cholesterol
D. DNA thymine bases

A. Cellular proteins

118

In therapeutic dosing, NAPQI is rendered safe primarily by conjugation with:
A. Sulfate
B. Glutathione
C. Glycine
D. Glucuronic acid

B. Glutathione

119

A chronic alcohol user develops severe acetaminophen toxicity at a lower dose. Best explanation?
A. Faster glucuronidation
B. Less CYP activity
C. More NAPQI shunting
D. More renal clearance

C. More NAPQI shunting

120

Chronic alcohol use increases acetaminophen toxicity risk by increasing levels of:
A. CYP2E1
B. CYP2A1
C. CYP3A4
D. UGT1A1

A. CYP2E1

121

A patient with acetaminophen poisoning receives an antidote that restores glutathione availability. Which treatment is listed?
A. Fomepizole
B. N-acetylcysteine
C. Deferoxamine
D. Atropine

B. N-acetylcysteine

122

N-acetylcysteine helps most directly by:
A. Inhibiting CYP active sites
B. Neutralizing NAPQI directly
C. Increasing glutathione stores
D. Increasing renal excretion

C. Increasing glutathione stores

123

During an overnight fast, blood glucose is maintained primarily by:
A. Gluconeogenesis
B. Glycolysis
C. Lipogenesis
D. Glycogenolysis

D. Glycogenolysis

124

If gluconeogenesis is required, how much ATP is needed to make one glucose from two pyruvate?
A. 6 ATP
B. 2 ATP
C. 4 ATP
D. 8 ATP

A. 6 ATP

125

During fasting gluconeogenesis, the energy to meet this ATP requirement is obtained mainly from:
A. Pentose phosphate pathway
B. Glycolysis
C. Fatty acid oxidation
D. Protein synthesis

C. Fatty acid oxidation

126

Compared with most organs, the liver has a much greater demand for:
A. NADH
B. FADH2
C. ATP
D. NADPH

D. NADPH

127

The only organ that can produce ketone bodies is the:
A. Liver
B. Brain
C. Heart
D. Kidney

A. Liver

128

Despite producing ketone bodies, the liver is listed as being unable to:
A. Export ketones
B. Synthesize ketones
C. Sense circulating ketones
D. Use ketones for energy

D. Use ketones for energy

129

Hypoproteinemia causes edema primarily because of:
A. Increased plasma oncotic pressure
B. Decreased lymph formation
C. Low plasma oncotic pressure
D. Reduced capillary permeability

C. Low plasma oncotic pressure

130

Hepatic NADPH is used for biosynthesis of:
A. Urea and creatinine
B. Heme and globin
C. DNA and RNA
D. Fatty acids, cholesterol, bile salts

D. Fatty acids, cholesterol, bile salts

131

Cirrhosis causes portal hypertension that increases back pressure into esophageal veins, promoting:
A. Splenic infarction
B. Esophageal varices
C. Renal vein thrombosis
D. Pulmonary edema

B. Esophageal varices

132

In cirrhosis, reduced coagulation protein synthesis and impaired vitamin K–dependent reactions most directly produce:
A. Prolonged prothrombin time
B. Shortened prothrombin time
C. Prolonged bleeding time
D. Shortened aPTT

A. Prolonged prothrombin time

133

When hepatocellular function is compromised, urea-cycle capacity is inadequate and peripheral ammonium contributes to:
A. Wernicke encephalopathy
B. Parkinson disease
C. Hepatic encephalopathy
D. Guillain-Barré syndrome

C. Hepatic encephalopathy

134

The most abundant plasma protein produced by the liver is:
A. Fibrinogen
B. Albumin
C. Transferrin
D. Ceruloplasmin

B. Albumin

135

Most sugars secreted by the liver onto proteins are:
A. O-linked glycans
B. N-linked glycans
C. Lipid anchors
D. Phosphate tags

A. O-linked glycans

136

O-linked carbohydrate attachment occurs via the –OH of:
A. Lysine or arginine
B. Aspartate or glutamate
C. Glycine or proline
D. Serine or threonine

D. Serine or threonine

137

A particularly important O-linked sugar made by the liver is:
A. Ribose
B. Mannose
C. N-acetylneuraminic acid
D. Galactose

C. N-acetylneuraminic acid

138

NANA is synthesized from:
A. Fructose-6-P + PEP
B. Glucose-6-P + citrate
C. Pyruvate + ribose-5-P
D. Acetyl-CoA + OAA

A. Fructose-6-P + PEP

139

As serum proteins age, loss of NANA residues signals:
A. Increased half-life
B. Nuclear sequestration
C. Bile conjugation
D. Clearance and degradation

D. Clearance and degradation

140

Major functions of the pentose phosphate pathway include generation of:
A. NADH and acetyl-CoA
B. NADPH and pentoses
C. ATP and lactate
D. FADH2 and succinate

B. NADPH and pentoses

141

The liver consumes approximately what fraction of the body’s total oxygen?
A. About 5%
B. About 10%
C. About 20%
D. About 35%

C. About 20%

142

After a binge, which organ is the major site of ethanol oxidation?
A. Kidney
B. Liver
C. Brain
D. Skeletal muscle

B. Liver

143

Hepatic ethanol oxidation yields principally acetate, then which product?
A. Lactate
B. Pyruvate
C. Acetaldehyde
D. Acetyl-CoA

D. Acetyl-CoA

144

Hepatic glucose use rate is partly determined by activity of which enzyme?
A. Hexokinase
B. PFK-1
C. Glucokinase
D. Glycogen phosphorylase

C. Glucokinase

145

The glucokinase regulatory protein is located primarily in the:
A. Nucleus
B. Cytosol
C. Mitochondria
D. Smooth ER

A. Nucleus

146

In liver, glucokinase activity is regulated by binding to:
A. Insulin receptor
B. Glucokinase regulatory protein
C. PFK-2
D. GLUT4 transporter

B. Glucokinase regulatory protein

147

During fasting, the major lipids oxidized as hepatic fuels are:
A. Long-chain fatty acids
B. Ketone bodies
C. Medium-chain fatty acids
D. Short-chain fatty acids

A. Long-chain fatty acids

148

Palmitic, stearic, and oleic acids are major lipids ingested mainly from:
A. Fruits
B. Grains
C. Meat or dairy
D. Leafy vegetables

C. Meat or dairy

149

Fatty acids in infants usually enter via maternal milk as:
A. Free fatty acids
B. Phospholipids
C. Cholesteryl esters
D. Medium-chain triacylglycerols

D. Medium-chain triacylglycerols

150

MCT supplements help malabsorption patients mainly because they provide:
A. Easily absorbed calories
B. Increased bile salt production
C. Increased lymphatic transport
D. Enhanced pancreatic lipase activity

A. Easily absorbed calories

151

A child with steatorrhea from low pancreatic enzymes needs calories. Best supplement?
A. MCTs
B. Long-chain triglycerides
C. Fish oil capsules
D. Cholesterol esters

A. MCTs

152

A patient with cholestasis and low intraluminal bile salts needs calories. Best fat source?
A. Long-chain triglycerides
B. MCT supplements
C. Plant sterols
D. Omega-3 phospholipids

B. MCT supplements

153

A stone obstructs the common bile duct causing fat malabsorption. Best calorie fat?
A. MCT supplements
B. Long-chain triglycerides
C. Cholesterol esters
D. Wax esters

A. MCT supplements

154

Compared with other tissues, peroxisomes are present in greatest numbers in:
A. Liver
B. Heart
C. Brain
D. Skeletal muscle

A. Liver

155

Oxidation of very-long-chain fatty acids (e.g., C24:0) occurs primarily in:
A. Mitochondria
B. Smooth ER
C. Peroxisomes
D. Cytosol

C. Peroxisomes

156

Peroxisomes detoxify which reactive molecule using catalase?
A. Superoxide
B. Nitric oxide
C. Peroxynitrite
D. Hydrogen peroxide

D. Hydrogen peroxide

157

Cleavage of the cholesterol side chain for bile salt synthesis occurs in:
A. Lysosomes
B. Mitochondria
C. Peroxisomes
D. Golgi apparatus

C. Peroxisomes

158

A step in ether lipid biosynthesis occurs in the:
A. Rough ER
B. Peroxisome
C. Cytosol
D. Nucleus

B. Peroxisome

159

Several steps of arachidonic acid metabolism occur in:
A. Mitochondria
B. Golgi
C. Peroxisomes
D. Ribosomes

C. Peroxisomes

160

The key peroxisomal enzyme that detoxifies hydrogen peroxide is:
A. Catalase
B. Myeloperoxidase
C. Xanthine oxidase
D. Glutathione reductase

A. Catalase

161

A neonate has a cerebrohepatorenal (Zellgewer) syndrome due to absence of which organelle?
A. Lysosomes
B. Mitochondria
C. Smooth ER
D. Peroxisomes

D. Peroxisomes

162

In Zellweger syndrome, which fatty acids accumulate in brain tissue?
A. C8 to C12
B. C26 to C38
C. C14 to C18
D. C2 to C4

B. C26 to C38

163

In Zellweger syndrome, there is defective oxidation of very-long-chain fatty acids used for:
A. ATP synthesis
B. Myelin formation
C. Steroid receptors
D. Glycogen storage

B. Myelin formation

164

PPARs were named because agonists can induce hepatic:
A. Glycogen depletion
B. Ketone breakdown
C. Bile flow
D. Peroxisome proliferation

D. Peroxisome proliferation

165

Which PPAR isoform is the major form in liver?
A. PPAR-α
B. PPAR-γ
C. PPAR-δ/β
D. PPAR-ε

A. PPAR-α

166

A patient with hypertriglyceridemia starts clofibrate. This drug class binds:
A. LXR
B. FXR
C. SREBP-1c
D. PPARs

D. PPARs

167

Fibrates are typically prescribed for patients with:
A. Low HDL
B. Elevated triglycerides
C. Elevated LDL only
D. Isolated hyperuricemia

B. Elevated triglycerides

168

Fibrate therapy lowers triglycerides primarily by increasing:
A. Cholesterol esterification
B. ApoB-48 synthesis
C. Triglyceride oxidation
D. De novo lipogenesis

C. Triglyceride oxidation

169

Suppressing apoCIII levels lowers plasma triglycerides by allowing more:
A. IDL endocytosis
B. HDL secretion
C. VLDL assembly
D. Chylomicron formation

A. IDL endocytosis

170

The glycine conjugate of salicylate is called:
A. Hippurate
B. Glycocholate
C. Salicylurate
D. Urobilinogen

C. Salicylurate

171

A child develops vomiting and progressive CNS dysfunction after a viral illness. Diagnosis?
A. Wilson disease
B. Reye syndrome
C. Acute pancreatitis
D. Crigler–Najjar syndrome

B. Reye syndrome

172

Reye syndrome is classically associated with children using which drug during viral illness?
A. Ibuprofen
B. Acetaminophen
C. Aspirin
D. Diphenhydramine

C. Aspirin

173

Autopsy in fatal Reye syndrome most characteristically shows:
A. Swollen disrupted mitochondria
B. Portal vein thrombosis
C. Bridging collagen septa
D. Iron-laden hepatocytes

A. Swollen disrupted mitochondria

174

Reye syndrome autopsy also shows fatty vacuolization in:
A. Heart and spleen
B. Brain and pancreas
C. Liver and renal tubules
D. Lung and marrow

C. Liver and renal tubules

175

A cirrhotic patient has elevated circulating nonesterified fatty acids. Which marker is high?
A. LDL cholesterol
B. ApoA-I
C. LCAT activity
D. NEFA

D. NEFA

176

Hepatocyte injury releases which enzymes, elevating them in plasma?
A. ALP and GGT
B. ALT and AST
C. CK and troponin
D. Amylase and lipase

B. ALT and AST

177

In liver disease, jaundice most directly reflects impaired:
A. Heme synthesis
B. Bilirubin glucuronidation
C. Bile acid reuptake
D. Albumin degradation

B. Bilirubin glucuronidation

178

A major change that occurs when fibrosis is initiated is that the normally “sparse” or “leaky” basement membrane between the endothelial cell and the hepatocyte is replaced with a high-density membrane containing
A. Laminin
B. Elastin
C. Keratin
D. Fibrillar collagen

D. Fibrillar collagen

179

Peroxisome Proliferator-Activated Receptors (PPARs) are a family of nuclear receptor proteins that function as ______ ______ regulating gene expression related to lipid metabolism, glucose homeostasis, and cell differentiation.

transcription factors

180

PPARα: Highly expressed in the liver, heart, and muscle, it regulates ______ ______ oxidation.

fatty acid