UTILIZATION OF KETONE BODIES (Ketolysis)

UTILIZATION OF KETONE BODIES (Ketolysis)

• Ketone bodies are water-soluble and easily transported from the liver to other tissues where they Are oxidized.

• Acetoacetate and B-hydroxybutyrate are the alternative fuel for cells of tissues like -

• Skeletal muscles

• Cardiac muscles

• Renal cortex

• Brain

The tissues which lack mitochondria can not utilize ketone bodies. Ketone body production and utilization are increased when glucose supply is short in tissues, e.g. in prolonged starvation, uncontrolled diabetes mellitus.

In prolonged starvation, ketone bodies are the major fuel for the brain,

• Oxidation of B-hydroxybutyrate produces acetoacetate, catalyzed by enzyme B-hydroxybutyrate Dehydrogenase.

- It is a reversal of the synthetic reaction.

Acetoacetate is activated to acetoacetyl CoA by enzyme thiophorase, CoA is donated by succinyl CoA. * Thiophorase is absent in the liver; that's why the liver cannot utilize ketone body as an energy source. Acetoacetyl CoA is cleaved by the enzyme thiolase to form two molecules of acetyl CoA, which is oxidized via the TCA cycle.

• Acetoacetate gives 2 molecules of acetyl CoA i.e. (10 x 2) = 20 ATP

• B-hydroxybutyrate also gives 2 molecules of acetyl CoA i.e. (10 x 2) = 20 ATP. • Conversion of B-hydroxybutyrate to acetoacetate yields an NADH + H molecule, which in turn gives 2.5 more ATP

So, B-hydroxybutyrate gives (20 + 2.5) = 22.5 ATP.

The reactivation reaction requires equivalent to 1 mole of ATP.

Therefore, oxidation of acetoacetate yields nets 19 moles and B-hydroxybutyrate 21.5 moles of ATP.

utilization and oxidation in extrahepatic tissues

• The reactivation of acetoacetate to acetoacetyl CoA occurs in two separate paths.

- One catalyzed by a thiokinase in the presence of CoA and ATP

- Other by CoA transferase (thiophorase) in the presence of succinyl CoA.

In muscle, the latter is the predominant process.

• What is ketosis?