Ketone Bodies

What are ketone bodies?

Molecules that serve as alternative energy source to brain, heart and skeletal muscles when there is low glucose availability

What is the biosynthesis of ketone bodies called?

Ketogenesis

Where does ketogenesis occur?

Mitochondria of hepatocytes (liver cells)

What is the main concept of ketogenesis?

Liver mitochondria converts acetyl-CoA derived from FA oxidation into KB

What are the 3 primary ketone bodies?

• Acetoacetate

• B-hydroxybutyrate

• Acetone

Acetoacetate

• Characteristic

• Can be converted to

Characteristic: Primary ketone formed in liver

Can be converted to:

• B-hydroxybutyrate for transport

• Acetone, byproduct expelled through breath or urine

B-hydroxybutyrate

• Characteristic

• Formed from

• Provides

Characteristic: Most abundant KB in circulation

Formed from: Reduction of acetoacetate

Provides: Energy upon oxidation back to acetoacetate

Acetone

• What kind of byproduct

• Characteristic

• Excreted via

Kind of byproduct: Non-metabolizable

Characteristic: Volatile and gives fruity smell

Excreted via: Breath or urine

What are the 2 regulation processes of KB production?

• Ketogenesis

• Ketolysis

Ketogenesis

• What

• Stimulated during

• What are the 4 steps

What: The process where the liver produces KB

Stimulated during: Conditions where glucose is insufficient such as

• Prolonged fasting

• Low carbohydrate diets

• Uncontrollled diabetes mellitus

Steps:

1. Condensation of acetyl-CoA

   1. By the fusion of 2 acetyl-CoA forming acetoacetyl-CoA

   2. Enzyme: Thiolase

2. Formation of HMG-CoA

   1. By the fusion of acetoacetyl-CoA and another acetyl-CoA forming HMG-CoA

   2. Enzyme: HMG-CoA synthase

3. Production of acetoacetate

   1. Degradation of MHG-CoA into acetoacetate + acetyl CoA

   2. Enzyme: HMG-CoA lyase

4. Conversion to other KBs

   1. Conversion of acetoacetate into either

      1. Beta-hydroxybutyrate

      2. OR acetone

Ketolysis

• What

• Occurs when

• KB released in

• Transported to and occurs in

  • BUT NOT

• Enzyme required

  • Location

  • Except

.

What: Process where tissues utilize KB as an energy source

Occurs when: Glucose and insulin levels are lowered

KB released in: Bloodstream

Transported to and occurs in: Brain, heart and muscles

• BUT NOT: heptaocytes

Required enzyme: SCOT enzyme (thiophorase)

• Location: Mitochondria

• Except: Hepatocytes

Clinical Relevance: What is ketosis?

Normal metabolic state during fasting or carbohydrate restriction where KB are elevated in blood

What can ketosis in bovine lead to?

• Bovine ketoacidosis

• NEB (negative energy balance)

• Milk production

Bovine ketoacidosis

• Affects during

• Characterised by

• Occurs when

Affects: High-producing dairy cows during early lactation

Characterised by: Elevated ketone body levels in due to negative energy balance (NEb)

• Blood

• Urine

• Milk

Occurs when: Energy demands such as high milk production exceed energy intake, leading to low blood glucose concentration

What can ketosis in small ruminants lead to?

• Pregnancy toxemia

• Pregnancy

• Multiple fetuses

What can ketosis in companion animals lead to?

• Diabetic ketoacidosis

• Hormonal

• Insulin deficiency

Clinical Relevance: What is ketoacidosis?

A pathological state where excessive ketone production leads to acidic blood pH