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Biochem 44

front 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

back 1

B. Pit NK cells

front 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

back 2

A. Smooth ER

front 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

back 3

D. Phase I

front 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

back 4

C. Phase II

front 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

back 5

D. CYP3A4 inhibition

front 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

back 6

B. Free radical

front 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

back 7

A. CYP2E1

front 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

back 8

C. Reduced glutathione

front 9

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

back 9

B. Guanine

front 10

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

back 10

D. Hepatic angiosarcoma

front 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

back 11

A. Aspergillus flavus

front 12

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

back 12

C. p53

front 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

back 13

C. CYP2A1

front 14

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

back 14

B. Guanine

front 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

back 15

D. Lysine

front 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

back 16

A. Glutathione

front 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

back 17

D. Sulfation and glucuronidation

front 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

back 18

C. NAPQI

front 19

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

back 19

A. CYP2E1

front 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

back 20

B. More CYP2E1 activity

front 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

back 21

C. Decreases hepatic synthesis

front 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

back 22

D. Liver

front 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

back 23

B. Glutamine and alanine

front 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

back 24

A. Ammonium ion

front 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

back 25

C. Systemic ammonium reaches brain

front 26

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

back 26

D. CYP2E1

front 27

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

back 27

A. Smooth ER P450s

front 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

back 28

B. N-acetylneuraminic acid

front 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

back 29

D. O-linked sugar

front 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

back 30

C. 15-fold

front 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

back 31

A. Adds negative charged group

front 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

back 32

B. Pit NK cells

front 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

back 33

B. Loss of NANA residues

front 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

back 34

D. Pentose phosphate pathway

front 35

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

back 35

A. Glutathione reductase

front 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

back 36

C. GSSG → GSH

front 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

back 37

B. Free radical injury defense

front 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

back 38

A. Pentose phosphate pathway

front 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

back 39

D. High Km for both proteins

front 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

back 40

C. Nucleus; GK regulatory protein

front 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

back 41

B. Increases

front 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

back 42

A. Long-chain fatty acids

front 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

back 43

D. Peroxisomal membrane

front 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

back 44

C. PPAR

front 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

back 45

A. PPARα

front 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

back 46

B. Medium-chain fatty acyl-CoA enzyme

front 47

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

back 47

D. Glycine

front 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

back 48

C. LPL and hepatic TG lipase

front 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

back 49

A. lecithin-cholesterol acyltransferase

front 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

back 50

B. Kidney and gut

front 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

back 51

D. Portal vein

front 52

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

back 52

C. Kidney

front 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

back 53

A. Sinusoids

front 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

back 54

B. Endothelial cells

front 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

back 55

D. Bile

front 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

back 56

C. Common bile duct

front 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

back 57

A. Connective tissue capsule

front 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

back 58

B. Hepatocytes

front 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

back 59

C. Stimulated growth after damage

front 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

back 60

D. Kupffer cells

front 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

back 61

B. Sialic acid

front 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

back 62

D. Glutathione reductase

front 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

back 63

A. C20–C26

front 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

back 64

C. Hippurate

front 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

back 65

B. Elevated triglycerides

front 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

back 66

A. Glycolysis

front 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

back 67

C. GLUT2

front 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

back 68

C. Hepatic artery

front 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

back 69

A. Kupffer cells

front 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

back 70

B. Ito cells

front 71

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

back 71

C. Stellate cells

front 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

back 72

D. Stellate cells

front 73

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

back 73

B. Extracellular matrix material

front 74

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

back 74

A. Stellate cells

front 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

back 75

B. Natural killer cells

front 76

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

back 76

A. Natural killer cells

front 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

back 77

B. Urine or bile

front 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

back 78

B. Enterohepatic circulation

front 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

back 79

C. Coagulation proteins

front 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

back 80

A. Heme, purines, pyrimidines

front 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

back 81

B. Metabolic product

front 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

back 82

B. Basement membrane

front 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

back 83

A. Exchange between blood and hepatocytes

front 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

back 84

B. Converts amino acids to multiple fuels

front 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

back 85

A. Glucose, fatty acids, ketones

front 86

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

back 86

IDL

front 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

back 87

D. VLDL

front 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

back 88

B. Phospholipids and cholesterol

front 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

back 89

B. Asialoglycoprotein receptor

front 90

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

back 90

A. Hepatic binding protein

front 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

back 91

C. No nutrient value

front 92

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

back 92

B. Liver

front 93

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

back 93

B. Lipophilic

front 94

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

back 94

B. Introduce hydroxyl reactive sites

front 95

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

back 95

B. Negatively charged group

front 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

back 96

A. Glycine, sulfate, glucuronic acid

front 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

back 97

A. Sulfation

front 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

back 98

A. Benzopyrene

front 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

back 99

A. Heterocyclic rings

front 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

back 100

A. Steroids

front 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

back 101

B. Oxidize substrates, add oxygen

front 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

back 102

C. CYP3A4

front 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

back 103

B. Grapefruit inhibits CYP3A4

front 104

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

back 104

B. CYP3A4

front 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

back 105

A. CYP3A4

front 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

back 106

A. NADPH

front 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

back 107

A. Integral membrane localization within smooth ER lipid bilayer

front 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

back 108

A. Inducible by own substrate

front 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

back 109

D. Free radical intermediate

front 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

back 110

B. Plastics

front 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

back 111

C. Hepatic angiosarcoma

front 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

back 112

A. CYP can bioactivate toxins

front 113

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

back 113

D. CYP2A1

front 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

back 114

C. Glucuronidation or sulfation

front 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

back 115

B. Conjugation pathways become saturated

front 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

back 116

D. N-acetyl-p-benzoquinoneimine

front 117

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

back 117

A. Cellular proteins

front 118

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

back 118

B. Glutathione

front 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

back 119

C. More NAPQI shunting

front 120

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

back 120

A. CYP2E1

front 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

back 121

B. N-acetylcysteine

front 122

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

back 122

C. Increasing glutathione stores

front 123

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

back 123

D. Glycogenolysis

front 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

back 124

A. 6 ATP

front 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

back 125

C. Fatty acid oxidation

front 126

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

back 126

D. NADPH

front 127

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

back 127

A. Liver

front 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

back 128

D. Use ketones for energy

front 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

back 129

C. Low plasma oncotic pressure

front 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

back 130

D. Fatty acids, cholesterol, bile salts

front 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

back 131

B. Esophageal varices

front 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

back 132

A. Prolonged prothrombin time

front 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

back 133

C. Hepatic encephalopathy

front 134

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

back 134

B. Albumin

front 135

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

back 135

A. O-linked glycans

front 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

back 136

D. Serine or threonine

front 137

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

back 137

C. N-acetylneuraminic acid

front 138

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

back 138

A. Fructose-6-P + PEP

front 139

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

back 139

D. Clearance and degradation

front 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

back 140

B. NADPH and pentoses

front 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%

back 141

C. About 20%

front 142

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

back 142

B. Liver

front 143

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

back 143

D. Acetyl-CoA

front 144

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

back 144

C. Glucokinase

front 145

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

back 145

A. Nucleus

front 146

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

back 146

B. Glucokinase regulatory protein

front 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

back 147

A. Long-chain fatty acids

front 148

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

back 148

C. Meat or dairy

front 149

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

back 149

D. Medium-chain triacylglycerols

front 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

back 150

A. Easily absorbed calories

front 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

back 151

A. MCTs

front 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

back 152

B. MCT supplements

front 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

back 153

A. MCT supplements

front 154

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

back 154

A. Liver

front 155

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

back 155

C. Peroxisomes

front 156

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

back 156

D. Hydrogen peroxide

front 157

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

back 157

C. Peroxisomes

front 158

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

back 158

B. Peroxisome

front 159

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

back 159

C. Peroxisomes

front 160

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

back 160

A. Catalase

front 161

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

back 161

D. Peroxisomes

front 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

back 162

B. C26 to C38

front 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

back 163

B. Myelin formation

front 164

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

back 164

D. Peroxisome proliferation

front 165

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

back 165

A. PPAR-α

front 166

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

back 166

D. PPARs

front 167

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

back 167

B. Elevated triglycerides

front 168

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

back 168

C. Triglyceride oxidation

front 169

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

back 169

A. IDL endocytosis

front 170

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

back 170

C. Salicylurate

front 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

back 171

B. Reye syndrome

front 172

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

back 172

C. Aspirin

front 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

back 173

A. Swollen disrupted mitochondria

front 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

back 174

C. Liver and renal tubules

front 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

back 175

D. NEFA

front 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

back 176

B. ALT and AST

front 177

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

back 177

B. Bilirubin glucuronidation

front 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

back 178

D. Fibrillar collagen

front 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.

back 179

transcription factors

front 180

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

back 180

fatty acid