Lecture 18: Fuels

Describe the catabolism of fatty acids, focusing on beta-oxidation and energy yield

Beta-oxidation is the main pathway for fatty acid (long hydrocarbon chains with an even number of carbon atoms) catabolism.

During beta-oxidation, he fatty acid chain is divided into two-carbon units forming acetyl-CoA, which enters the Krebs cycle.

Energy yield:

• Fatty acids yield about 3 times more ATP than glucose

• Oxidation requires 5 times more oxygen compared to glucose → occurs only under aerobic conditions

Excess acetyl-CoA (esp. during fasting/starvation) leads to ketone body formation in the liver.

Why can the body not store excess amino acids?

• No storage form for amino acids (unlike glycogen or triglycerides)

• Excess dietary amino acids are sent to the liver for deamination

What is the process of deamination and the fate of nitrogen-containing compounds?

• Deamination: removal of the amino group (–NH₂) from the amino acid

• The amino acid group becomes ammonia (NH₃) → converted to urea → excreted via urine

• The remaining carbon skeleton becomes keto acid

What is the metabolic fates of the resulting carbon skeletons?

• Glucogenic amino acids → converted to pyruvate or TCA intermediates → glucose synthesis (gluconeogenesis)

• Ketogenic amino acids → converted to acetyl-CoA or ketone bodies

• Occurs during fasting/starvation to maintain glucose for brain and red blood cells

Compare and contrast ATP production mechanisms under aerobic and anaerobic conditions

Condition	Pathway	ATP Yield	Substrates Used
Aerobic	Glycolysis → TCA → ETC	~32–34 ATP/glucose	Glucose, fatty acids, amino acids
Anaerobic	Glycolysis + fermentation	2 ATP/glucose	Glucose only (→ lactic acid)

• Fatty acids cannot be used anaerobically (require mitochondria and O₂)

• Amino acids (glucogenic) may support anaerobic glycolysis indirectly via pyruvate

Compare substrate utilisation in skeletal muscle, cardiac muscle, brain, and red blood cells

Tissue	Preferred Substrate	Notes
Skeletal Muscle	Fatty acids at rest, glucose during activity	Uses ketone bodies during starvation.
Cardiac Muscle	Fatty acids (even during fed state)	Very energy-demanding; prefers FA due to high ATP yield.
Brain	Glucose (always prioritized)	Can switch to ketone bodies during starvation; cannot use FA directly.
Red Blood Cells	Glucose only	No mitochondria; rely on anaerobic glycolysis.

Explain how tissue-specific preferences for metabolic substrates change during fed, fasting, and starvation states

State	Fuel Availability	Tissue Utilization Trends
Fed (0–4 h)	High glucose	Liver stores glucose as glycogen; brain and RBCs use glucose; muscle may use glucose or FA
Fasting (4–30 h)	Low glucose, glycogen mobilization	Liver breaks glycogen; brain still uses glucose; muscles shift to FA; AA → glucose in liver
Starvation (>30 h)	Very low glucose, high FA and ketones	Brain uses ketones, RBCs use glucose; muscles/kidneys use FA; proteins catabolized (muscle loss)

• Glucose prioritisation: always for brain and red blood cells first

• Ketone bodies: produced in liver from excess acetyl-CoA (from fatty acid oxidation)

• Muscle wastage in starvation: amino acids from muscle are used for gluconeogenesis