A healthy adult is 34 hours into fasting. Liver glycogen is depleted. What now maintains blood glucose?
A. Muscle glycogen breakdown
B. Hepatic glycogenolysis
C. Hepatic gluconeogenesis
D. Intestinal glucose absorption

C. Hepatic gluconeogenesis

Gluconeogenesis is glucose synthesis primarily from:
A. Noncarbohydrate precursors
B. Stored liver glycogen
C. Dietary polysaccharides
D. Ketone bodies only

A. Noncarbohydrate precursors

In humans, gluconeogenesis occurs primarily in:
A. Skeletal muscle cytosol
B. Brain astrocytes mainly
C. Adipose tissue mainly
D. Liver hepatocytes mainly

D. Liver hepatocytes mainly

Which is a major gluconeogenic precursor?
A. Palmitate
B. Lactate
C. Cholesterol
D. Acetyl-CoA

B. Lactate

The amino acid highlighted as a key gluconeogenic precursor is:
A. Alanine
B. Leucine
C. Lysine
D. Isoleucine

A. Alanine

Relative to glycolysis, gluconeogenesis requires:
A. No unique reactions
B. Only one bypass step
C. Complete enzyme replacement
D. Three bypass reactions

D. Three bypass reactions

After stopping food intake, liver glycogen breakdown begins to support blood glucose after about:
A. 15 minutes
B. 2–3 hours
C. 12–18 hours
D. 3–5 days

B. 2–3 hours

During an overnight fast, blood glucose is maintained mainly by:
A. Glycolysis plus lipogenesis
B. Ketolysis plus proteolysis
C. Glycogenolysis plus gluconeogenesis
D. Glycogenesis plus lipolysis

C. Glycogenolysis plus gluconeogenesis

As glycogen stores fall, adipose triacylglycerol breakdown provides:
A. Fatty acids and glycerol
B. Glucose and lactate
C. Ketones and glucose
D. Pyruvate and alanine

A. Fatty acids and glycerol

During fasting, fatty acids primarily help by:
A. Converting directly to glucose
B. Providing alternative fuel
C. Becoming DHAP in liver
D. Becoming lactate for liver

B. Providing alternative fuel

After ~30 hours of fasting, the only source of blood glucose is:
A. Muscle glycogenolysis
B. Dietary absorption
C. Hepatic glycogenolysis
D. Hepatic gluconeogenesis

D. Hepatic gluconeogenesis

Under extreme starvation, an additional site of gluconeogenesis is the:
A. Pancreatic islets
B. Renal medulla
C. Renal cortex
D. Splenic red pulp

C. Renal cortex

In extreme starvation, glucose produced by the kidney is mainly used by the:
A. Cerebral cortex neurons
B. Renal medulla cells
C. Hepatic stellate cells
D. Skeletal myocytes

B. Renal medulla cells

Most gluconeogenic steps mirror glycolysis, but overall:
A. Carbon flow is unchanged
B. Carbon flow is cyclic
C. Carbon flow is forward
D. Carbon flow is reversed

D. Carbon flow is reversed

Glycerol carbons are gluconeogenic because they form:
A. Dihydroxyacetone phosphate
B. Acetyl-CoA carbons
C. Citrate cycle intermediate
D. Oxaloacetate intermediate

A. Dihydroxyacetone phosphate

A hepatocyte uses glycolytic intermediates to generate glycerol 3-phosphate. Its key role is:
A. Acetyl-CoA backbone
B. Lactate backbone
C. Triacylglycerol backbone
D. Ketone body backbone

C. Triacylglycerol backbone

Liver triacylglycerols are secreted into blood primarily in:
A. HDL
B. LDL
C. Chylomicrons
D. VLDL

D. VLDL

Measuring ketones in blood and urine can indicate:
A. Starvation severity or DKA
B. Hyperthyroidism severity
C. Chronic liver failure only
D. SIADH severity

A. Starvation severity or DKA

A comatose patient has “fruity” breath. In DKA, the odor is due to:
A. Lactate
B. Acetone
C. Ammonia
D. Ethanol

B. Acetone

The “acetone” breath odor is linked to breakdown of which ketone body?
A. β-hydroxybutyrate
B. Propionyl-CoA
C. Acetoacetate
D. Oxaloacetate

C. Acetoacetate

Deep, relatively rapid respirations in DKA are termed:
A. Kussmaul respirations
B. Cheyne–Stokes breathing
C. Biot respirations
D. Apneustic breathing

A. Kussmaul respirations

Kussmaul respirations occur primarily because:
A. Hypoglycemia stimulates pons
B. Hypoxemia stimulates carotids
C. Fever stimulates medulla
D. Acidosis stimulates respiratory center

D. Acidosis stimulates respiratory center

The key gas exhaled more during Kussmaul compensation is:
A. HCO3−
B. CO2
C. Ketones
D. NH4+

B. CO2

Which paired finding most supports DKA coma over hypoglycemic coma?
A. Sweating, tremor
B. Confusion, hunger
C. Acetone breath, Kussmaul
D. Pallor, diaphoresis

C. Acetone breath, Kussmaul

Severe hyperglycemia in DKA causes polyuria mainly via:
A. Osmotic diuresis
B. SIADH effect
C. Nephrotic syndrome
D. Primary polydipsia

A. Osmotic diuresis

Volume depletion from DKA is commonly worsened by:
A. Polyphagia
B. Night sweats
C. Hemoptysis
D. Vomiting

D. Vomiting

A patient with DKA is volume depleted. Which hemodynamic profile fits best?
A. Hypertension, bradycardia, edema
B. Hypertension, bounding pulses, edema
C. Dehydration, hypotension, tachycardia
D. Bradycardia, hypothermia, pallor

C. Dehydration, hypotension, tachycardia

Why can ethanol carbons not support gluconeogenesis?
A. Ethanol forms glucose directly
B. Produces only acetyl-CoA
C. Produces only oxaloacetate
D. Produces only DHAP

B. Produces only acetyl-CoA

In liver, lactate and alanine contribute to gluconeogenesis by forming:
A. Pyruvate
B. Citrate
C. Palmitate
D. Cholesterol

A. Pyruvate

Which triacylglycerol component contributes carbon to gluconeogenesis?
A. Fatty acids
B. Sterol esters
C. Glycerol
D. Ketone bodies

C. Glycerol

A patient on a plant-heavy diet oxidizes an odd-chain fatty acid. The three ω-end carbons produce:
A. Acetyl-CoA
B. Succinyl-CoA
C. Propionyl-CoA
D. Pyruvate

C. Propionyl-CoA

Odd-chain fatty acids are obtained mainly from:
A. Vegetables
B. Dairy fat
C. Red meat
D. Fish oils

A. Vegetables

Propionyl-CoA is converted first to:
A. Succinyl-CoA
B. Acetoacetyl-CoA
C. Malonyl-CoA
D. Methylmalonyl-CoA

D. Methylmalonyl-CoA

Methylmalonyl-CoA is rearranged to:
A. Oxaloacetate
B. Succinyl-CoA
C. Malate
D. Citrate

B. Succinyl-CoA

In odd-chain fatty acid oxidation, net glucose can be made only from:
A. ω-end three carbons
B. Even-chain carbons
C. Acetyl-CoA carbons
D. Middle-chain carbons

A. ω-end three carbons

Why can acetyl-CoA not generate pyruvate for gluconeogenesis?
A. Pyruvate kinase is irreversible
B. PEPCK is irreversible
C. PDH reaction is irreversible
D. LDH blocks pyruvate formation

C. PDH reaction is irreversible

Which TCA reactions release the two CO2 that prevent net glucose from acetyl-CoA?
A. Citrate synthase, fumarase
B. Isocitrate DH, α-KGDH
C. Malate DH, aconitase
D. Succinate DH, thiolase

B. Isocitrate DH, α-KGDH

There is no net glucose synthesis from acetyl-CoA because:
A. Acetyl-CoA cannot enter TCA
B. OAA is fully consumed
C. NADH is always limiting
D. Two CO2 lost per turn

D. Two CO2 lost per turn

A 19-carbon fatty acid is oxidized. How many carbons form propionyl-CoA?
A. One
B. Two
C. Three
D. Four

C. Three

In a 19-carbon fatty acid, the remaining 16 carbons primarily form:
A. Acetyl-CoA
B. Pyruvate
C. Lactate
D. Glucose

A. Acetyl-CoA

In glycolysis, phosphoenolpyruvate is converted to pyruvate by:
A. PEP carboxykinase
B. Pyruvate kinase
C. Pyruvate carboxylase
D. Lactate dehydrogenase

B. Pyruvate kinase

Pyruvate carboxylase converts pyruvate to:
A. Citrate
B. Lactate
C. Acetyl-CoA
D. Oxaloacetate

D. Oxaloacetate

The enzyme that releases CO2 from OAA while generating PEP is:
A. PEP carboxykinase
B. Pyruvate kinase
C. Hexokinase
D. Citrate synthase

A. PEP carboxykinase

Oxaloacetate does not readily cross the:
A. Nuclear membrane
B. Lysosomal membrane
C. Mitochondrial membrane
D. Plasma membrane

C. Mitochondrial membrane

Because OAA cannot cross easily, it is often converted to:
A. Citrate or succinate
B. Glucose or glycogen
C. Acetyl-CoA or ketones
D. Malate or aspartate

D. Malate or aspartate

Glycerol enters gluconeogenesis at the level of:
A. Glucose 6-phosphate
B. DHAP
C. Citrate
D. Acetyl-CoA

B. DHAP

During rapid hepatic ethanol oxidation, the redox state shifts so:
A. NAD+/NADH increases
B. NADPH/NADP+ increases
C. NADH/NAD+ increases
D. FADH2/FAD increases

C. NADH/NAD+ increases

Elevated NADH inhibits glycerol use for gluconeogenesis because conversion to DHAP requires:
A. NAD+
B. ATP
C. Biotin
D. FAD

A. NAD+

High NADH drives lactate dehydrogenase toward producing:
A. Pyruvate
B. Oxaloacetate
C. Acetyl-CoA
D. Lactate

D. Lactate

After heavy alcohol intake, pyruvate generated from alanine is preferentially converted to:
A. Acetyl-CoA
B. Lactate
C. Citrate
D. Glucose

B. Lactate

A fasting patient binges alcohol and becomes hypoglycemic. Which precursors are least usable for gluconeogenesis?
A. Lactate, alanine, glycerol
B. Fatty acids, ketones, glycerol
C. Lactate, acetyl-CoA, ketones
D. Alanine, cholesterol, acetate

A. Lactate, alanine, glycerol

With high NADH, OAA is preferentially converted to:
A. PEP
B. Citrate
C. Malate
D. Succinyl-CoA

C. Malate

With high NADH, DHAP is preferentially converted to:
A. Pyruvate
B. Glycerol 3-phosphate
C. Lactate
D. Oxaloacetate

B. Glycerol 3-phosphate

A malnourished patient drinks heavily and then develops confusion and diaphoresis. Most likely metabolic outcome:
A. Hypernatremia
B. Metabolic alkalosis
C. Hyperglycemia
D. Hypoglycemia

D. Hypoglycemia

Fructose 1,6-bisphosphatase produces:
A. Fructose 1-phosphate
B. Fructose 6-phosphate
C. Fructose 2,6-bisphosphate
D. Glucose 1-phosphate

B. Fructose 6-phosphate

Glucose 6-phosphatase directly generates:
A. Glycogen
B. Glucose 6-phosphate
C. Lactate
D. Free glucose

D. Free glucose

Glucose 6-phosphatase is located in the:
A. Endoplasmic reticulum membrane
B. Mitochondrial matrix
C. Cytosolic ribosome
D. Nuclear envelope

A. Endoplasmic reticulum membrane

Which condition does NOT stimulate gluconeogenesis?
A. Prolonged exercise
B. High-protein diet
C. High-carbohydrate meal
D. Physiologic stress

C. High-carbohydrate meal

Which conversion is a regulated gluconeogenic “bypass”?
A. Lactate to pyruvate
B. PEP to pyruvate
C. Pyruvate to PEP
D. Glucose to G6P

C. Pyruvate to PEP

Which conversion is a regulated gluconeogenic “bypass”?
A. F1,6BP to F6P
B. F6P to F1,6BP
C. DHAP to G3P
D. G1P to glycogen

A. F1,6BP to F6P

Which conversion is a regulated gluconeogenic “bypass”?
A. Glucose to G6P
B. G6P to glycogen
C. F6P to F1,6BP
D. G6P to glucose

D. G6P to glucose

Hepatocytes should funnel PEP toward glucose during fasting. Which enzyme-state set best fits?
A. PDH↑ PC↓ PEPCK↓ PK↑
B. PDH↓ PC↑ PEPCK↑ PK↓
C. PDH↑ PC↑ PEPCK↓ PK↓
D. PDH↓ PC↓ PEPCK↑ PK↑

B. PDH↓ PC↑ PEPCK↑ PK↓

During conditions favoring gluconeogenesis, pyruvate dehydrogenase is typically:
A. Inactive
B. Active
C. Induced
D. Cleaved

A. Inactive

A fasting liver increases gluconeogenic capacity by inducing which enzyme quantity?
A. Pyruvate kinase
B. Phosphofructokinase-1
C. Hexokinase
D. PEP carboxykinase

D. PEP carboxykinase

A patient receives high-dose prednisone for vasculitis. Which lab abnormality is most expected?
A. Low blood glucose
B. High blood glucose
C. Low serum ketones
D. High serum lactate

B. High blood glucose

A fasting liver activates fructose 1,6-bisphosphatase. Which pair inhibits it allosterically?
A. Citrate and ATP
B. Glucose and insulin
C. F2,6BP and AMP
D. Pyruvate and NADH

C. F2,6BP and AMP

During fasting, hepatic ATP/NADH used for gluconeogenesis comes mainly from:
A. β-oxidation
B. Glycolysis
C. Glycogenesis
D. PPP flux

A. β-oxidation

An infant with a fatty-acid oxidation defect develops fasting hypoglycemia. Best mechanistic link?
A. Low hepatic glycogen
B. Low renal glucose
C. High insulin levels
D. Low hepatic energy

D. Low hepatic energy

Thirty minutes after a high-carbohydrate meal, glucose rises most typically to:
A. 65–75 mg/dL
B. 80–100 mg/dL
C. 120–140 mg/dL
D. 160–180 mg/dL

C. 120–140 mg/dL

After a typical meal, blood glucose returns to fasting range by about:
A. 30 minutes
B. 2 hours
C. 6 hours
D. 12 hours

B. 2 hours

A patient with severe hyperglycemia becomes bounded without ketones. Hyperosmolar coma stems mainly from:
A. Cerebral edema
B. Cerebral hemorrhage
C. Hepatic encephalopathy
D. Brain dehydration

D. Brain dehydration

About 2 hours after a meal, as glucose nears 80–100 mg/dL, the liver activates:
A. Glycogenolysis
B. Ketogenesis
C. Lipogenesis
D. Glycolysis

A. Glycogenolysis

After 5–6 weeks of starvation, blood glucose is closest to:
A. 90 mg/dL
B. 65 mg/dL
C. 45 mg/dL
D. 120 mg/dL

B. 65 mg/dL

Glucagon signaling in liver most directly raises intracellular:
A. IP3
B. DAG
C. cAMP
D. cGMP

C. cAMP

Glucagon raises hepatic cAMP by activating:
A. Protein kinase C
B. Guanylate cyclase
C. Tyrosine kinase
D. Adenylate cyclase

D. Adenylate cyclase

By ~4 hours after a meal, hepatic glucose output relies on glycogenolysis plus:
A. Gluconeogenesis
B. Glycolysis
C. Lipogenesis
D. Ketolysis

A. Gluconeogenesis

Glucagon prevents PEP from becoming pyruvate mainly by inactivating:
A. PEP carboxykinase
B. Pyruvate carboxylase
C. Pyruvate kinase
D. Lactate dehydrogenase

C. Pyruvate kinase

With pyruvate kinase inactivated, PEP “runs backward” to form:
A. Glucose 1-phosphate
B. Fructose 1,6-bisP
C. Acetyl-CoA
D. Lactate

B. Fructose 1,6-bisP

Enzymes unique to gluconeogenesis are most active under:
A. Fasting conditions
B. Postprandial conditions
C. After carbohydrate loading
D. During insulin surges

A. Fasting conditions

In fasting liver, acetyl-CoA from fatty acids directly activates:
A. Hexokinase
B. Pyruvate kinase
C. PFK-1
D. Pyruvate carboxylase

D. Pyruvate carboxylase

Which set is induced during fasting gluconeogenesis?
A. PFK-1, PK, LDH
B. PEPCK, FBPase, G6Pase
C. HK, PDH, CS
D. GCK, GS, GP

B. PEPCK, FBPase, G6Pase

Fructose 1,6-bisphosphatase is favored in fasting because:
A. AMP falls sharply
B. Citrate is absent
C. F2,6BP is low
D. NADH is low

C. F2,6BP is low

A carbon source explicitly used for gluconeogenesis is:
A. Glycerol
B. Palmitate
C. Cholesterol
D. Acetoacetate

A. Glycerol

During prolonged fasting, fatty acids are oxidized by tissues primarily to:
A. Lactate and ATP
B. Ketones and CO2
C. Glucose and ATP
D. CO2 and H2O

D. CO2 and H2O

After several days without food, the brain decreases glucose use by increasing:
A. Amino acid oxidation
B. Fatty acid oxidation
C. Ketone body use
D. Glycerol uptake

C. Ketone body use

After ~3–5 days fasting, brain glucose need is roughly:
A. Twice normal
B. One-third normal
C. Unchanged
D. One-tenth normal

B. One-third normal

Chronic hyperglycemia narrows microvessels mainly via protein:
A. Dephosphorylation
B. Proteolysis
C. Ubiquitination
D. Cross-linking

D. Cross-linking

Microvascular narrowing from chronic hyperglycemia classically targets:
A. Retina, glomeruli, nerves
B. Lung, marrow, spleen
C. Liver, skin, pancreas
D. Heart, brain, muscle

A. Retina, glomeruli, nerves

Narrowed renal glomerular microvessels most directly produce diabetic:
A. Retinopathy
B. Nephropathy
C. Neuropathy
D. Cardiomyopathy

B. Nephropathy

Narrowed microvessels to peripheral/autonomic nerves most directly produce diabetic:
A. Nephropathy
B. Retinopathy
C. Neuropathy
D. Dermopathy

C. Neuropathy

Fasting glucose 80–100 mg/dL is approximately:
A. ~2 mM
B. ~5 mM
C. ~8 mM
D. ~12 mM

B. ~5 mM

Post-meal glucose 120–140 mg/dL is approximately:
A. ~2 mM
B. ~5 mM
C. ~12 mM
D. ~8 mM

D. ~8 mM

Hepatic fructose 2,6-bisP levels are regulated by:
A. Insulin and glucagon
B. Cortisol and insulin
C. Epinephrine and ADH
D. Growth hormone and T3

A. Insulin and glucagon

After ~3–5 days fasting, brain glucose need is about:
A. 120 g/day
B. 80 g/day
C. 40 g/day
D. 10 g/day

C. 40 g/day