PHA 339 - Lecture #11 (Ketone Bodies)

Ketone bodies

Acetoacetate, β-hydroxybutyrate, and acetone

Location of ketogenesis

Liver mitochondria

Ketogenesis

Process of producing ketone bodies from acetyl-CoA

When ketogenesis occurs

Fasting, prolonged starvation, uncontrolled diabetes

Reason ketogenesis occurs

Excess acetyl-CoA from β-oxidation with low oxaloacetate availability

First step of ketogenesis

Condensation of two acetyl-CoA to form acetoacetyl-CoA

Rate-limiting enzyme of ketogenesis

HMG-CoA synthase

Intermediate of ketogenesis

HMG-CoA

Final products of ketogenesis

Acetoacetate and β-hydroxybutyrate

Acetone formation

Spontaneous decarboxylation of acetoacetate

Importance of ketone bodies

Alternative energy source for brain, muscle, and heart during fasting

Why liver cannot use ketone bodies

Lacks thiophorase (succinyl-CoA:acetoacetate CoA transferase)

Ketolysis

Conversion of ketone bodies back to acetyl-CoA in peripheral tissues

Location of ketolysis

Mitochondria of extrahepatic tissues

Importance of ketolysis

Provides energy during prolonged fasting

Diabetic ketoacidosis (DKA)

Excess ketone production causing metabolic acidosis

Cause of DKA

Uncontrolled type 1 diabetes with low insulin

Why DKA is dangerous

Severe metabolic acidosis, dehydration, electrolyte imbalance, possible coma

Kussmaul respirations

Deep, rapid breathing to compensate for metabolic acidosis

Fruity breath odor

Increased acetone in exhaled ai