ketogenesis

what is ketogenesis

• synthesis of ketone bodies

liver producing acetyl CoA by fatty acid breakdown is __________

• beta-oxidation

during a fasting state, the liver has elevated levels of _____

• fatty acid

elevated acetyl CoA levels cause upregulation of what enzyme? where is this enzyme seen?

• pyruvate carboxylase

  • gluconeogenesis

  • pyruvate → oxaloacetate

acetyl COA enters the ketogenic pathway instead of coupling with OAA to protect …

• OAA from entering gluconeogenesis

  • management of cellular resources

    • prevent loss of acetyl CoA

entry of acetyl-CoA into citric acid cycle requires _______

• oxaloacetate

when oxaloacetate is depleted, acetyl-CoA is converted into _______

• ketone bodies

  • low carb intake or diabetes

what are the 3 forms ketone bodies can leave the liver and are delivered by the blood to the various tissues

• acetone

  • eliminated in breathing

• acetoacetate

• beta-hydroxybutyrate

what organs use ketone bodies as a fuel source?

• cardiac muscle

• skeletal muscle

• renal cortex

• brain

steps of forming ketone bodies

1. 2 acetyl CoA → (thiolase) → acetoaccetyl CoA

2. acetoaccetyl CoA + acetyl-CoA → (HMG-COA synthase) → HMG CoA

3. HMG CoA → (HMG CoA lyase) → acetoacetate

   • acetyl-CoA leaves

4. a. acetoacetate → (acetodecarboxylase) → acetone

   b. acetoacetate → (D-beta-hydroxybutyrate dehydrogenase) → D-beta-hydroxybutyrate

the decarboxylation of acetoacetate results in the product ..

a) acetone

b) D-beta-hydroxybutyrate

c) acetoacetyl-CoA

d) acetyl-CoA

a) acetone

the reduction of acetoacetate results in the product ..

a) acetone

b) D-beta-hydroxybutyrate

c) acetoacetyl-CoA

d) acetyl-CoA

b) D-beta-hydroxybutyrate

what redox factor is used in the formation of ketone bodies? What step are they formed in?

1. NADH + H+ → NAD+

   • acetoacetate → (D-beta-hydroxybutyrate dehydrogenase) D-beta-hydroxybutyrate

steps to use ketone bodies as fuel

1. D-beta-hydroxybutyrate → (D-beta-hydroxybutyrate dehydrogenase) → acetoacetate

2. acetoacetate → (beta-ketoacyl-CoA transferase) → acetoacetyl-CoA

3. acetoacetyl-CoA → (thiolase) → 2 Acetyl CoA

what type of reaction is D-beta-hydroxybutyrate → acetoacetate ? what enzyme is used?

• D-beta-hydroxybutyrate dehydrogenase

• redox reaction

  • uses NAD+ → NADH + H+

what is used and released in the reaction acetoacetate → acetoacetyl-CoA ? what enzyme is used?

• (beta-ketoacyl-CoA transferase)

• succinyl-CoA used → releases succinate / GTP (Krebs Cycle)

what is the total ATP gain from using ketone bodies as fuel?

• 2 Acetyl-CoA = 12 ATP * 2 = 24 ATP

• NADH = 3 ATP

• GTP = 1 ATP

• total = 28 ATP