Tissue-Specific

4 min read Updated Apr 18, 2026

Tissues have specialized metabolic roles and fuel preferences. Knowing the characteristic fuel and function of each tissue helps you navigate MCAT passages.

Liver

The metabolic factory for the whole body.
Performs glycogenolysis, gluconeogenesis, ketogenesis, urea cycle, cholesterol and bile acid synthesis, lipoprotein assembly (VLDL), drug metabolism.
Fuel sources: amino acids, fatty acids, glucose, lactate, ethanol.
Unique enzymes: glucose-6-phosphatase (glucose export), HMG-CoA lyase (ketogenesis), PEPCK (gluconeogenesis), urea cycle enzymes.
Does NOT use ketone bodies as fuel (lacks thiophorase).

Skeletal Muscle

At rest: fatty acid oxidation.
During exercise: glycogen breakdown and glycolysis (often anaerobic → lactate during sprinting).
During starvation: adapts to use ketones; protein breakdown provides amino acids to liver for gluconeogenesis (glucose-alanine cycle).
Lacks glucose-6-phosphatase: muscle glycogen stays in muscle, does not contribute to blood glucose.
Lacks glucagon receptors: mobilizes via epinephrine.

Brain

Glucose is the primary fuel. ~120 g glucose/day under normal conditions.
Cannot use fatty acids (blood-brain barrier excludes them effectively).
In prolonged starvation: adapts to use ketone bodies for up to 75% of energy.
Tightly requires blood glucose - hypoglycemia causes rapid dysfunction.

Adipose Tissue

Stores triglycerides in fat droplets.
Fed state (insulin): lipoprotein lipase (LPL) at capillaries hydrolyzes circulating triglycerides; fatty acids enter adipocytes and re-esterified into triglyceride.
Fasting state (glucagon/epinephrine): hormone-sensitive lipase (HSL) breaks down stored triglycerides; fatty acids released to blood, bound to albumin, delivered to other tissues.
Glycerol released from adipose goes to liver for gluconeogenesis.

Heart

Cardiac muscle is highly aerobic (many mitochondria).
Preferred fuel: fatty acids (most of the time).
Also uses ketones well (always), lactate, and glucose.
Very flexible - can switch fuels based on availability.

Red Blood Cells

Lack mitochondria and nuclei.
Use glucose ONLY, via glycolysis.
Produce lactate continuously (sent to liver for Cori cycle).
Cannot use fatty acids, ketones, or amino acids for fuel.

Why do red blood cells rely entirely on glucose via glycolysis?

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RBCs lack mitochondria. They cannot use the TCA cycle, oxidative phosphorylation, or beta-oxidation. They also lack a nucleus and cannot synthesize new proteins. Their only ATP source is cytoplasmic glycolysis, converting glucose to lactate to regenerate NAD+. This produces ongoing lactate output that the liver recycles via the Cori cycle.

Why cannot muscle glycogen contribute directly to blood glucose?

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Muscle lacks glucose-6-phosphatase, the enzyme that removes phosphate from glucose-6-phosphate so free glucose can leave the cell. Muscle glycogen breakdown produces G6P that can only feed glycolysis locally. Only liver (and kidney cortex) have glucose-6-phosphatase and can release glucose to blood.

What fuel does the heart prefer under most conditions?

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Fatty acids. Cardiac muscle has abundant mitochondria and heavily depends on beta-oxidation. The heart also readily uses ketone bodies (always) and lactate (especially during rest). It is a metabolic generalist - can switch fuel sources based on availability. In ischemia, it switches to anaerobic glycolysis, building up lactate.