Biochem Final pt. 5 B-oxidation, ketone bodies, more tca / atp

Purpose of β-oxidation

Breaks down fatty acids into acetyl-CoA, NADH, and FADH₂ for energy production

Location of β-oxidation

Mitochondrial matrix

Activation of fatty acids

Fatty acid + CoA → fatty acyl-CoA (uses 2 ATP equivalents)

Transport of fatty acids into mitochondria

Carnitine shuttle (via carnitine acyltransferase I and II)

First step of β-oxidation

Oxidation by acyl-CoA dehydrogenase → forms a double bond → generates FADH₂

Second step of β-oxidation

Hydration by enoyl-CoA hydratase → adds water across double bond

Third step of β-oxidation

Oxidation by hydroxyacyl-CoA dehydrogenase → forms a ketone → generates NADH

Fourth step of β-oxidation

Thiolysis by thiolase → cleaves 2-carbon acetyl-CoA

Products per cycle of β-oxidation

1 FADH₂, 1 NADH, 1 Acetyl-CoA

Energy yield from palmitate (16C)

7 cycles → 8 acetyl-CoA, 7 NADH, 7 FADH₂

Special handling of monounsaturated fatty acids

Requires enoyl-CoA isomerase to fix cis-double bonds

Special handling of polyunsaturated fatty acids

Requires enoyl-CoA isomerase + 2,4-dienoyl-CoA reductase (uses NADPH)

Odd-chain fatty acids

final product is propionyl-CoA → converted to succinyl-CoA (requires Vitamin B₁₂)

Why odd-chain β-oxidation is unique

Only way fatty acid oxidation can contribute carbons directly to gluconeogenesis (via succinyl-CoA)

Definition of ketogenesis

Formation of ketone bodies from excess acetyl-CoA in liver mitochondria

When ketogenesis occurs

Fasting, starvation, prolonged exercise, low-carb diets, untreated Type 1 diabetes

Major ketone bodies

Acetoacetate, β-hydroxybutyrate, Acetone (minor, exhaled)

Purpose of ketone bodies

Provide an alternative energy source to glucose, especially for brain, heart, skeletal muscle

Conversion of ketone bodies back to energy

Acetoacetate and β-hydroxybutyrate converted back to acetyl-CoA → enter TCA cycle

Why ketones are useful

Water-soluble, easily transported in blood, spare glucose

Clinical problem: Ketoacidosis

Excessive ketone production → blood becomes acidic → can occur in uncontrolled diabetes or starvation

Link between β-oxidation, TCA, and ketogenesis

High β-oxidation → high acetyl-CoA; if oxaloacetate is low, acetyl-CoA diverted to ketone production

Energy comparison

Fatty acid oxidation yields more ATP per carbon than glucose oxidation

Regulation of fatty acid oxidation

Inhibited by malonyl-CoA (prevents β-oxidation during active fatty acid synthesis)