1. FATTY ACID OXIDATION Occurs inside mitochondria
Activation of Fatty acids
The first step occurs at the outer mito membrane by the acyl-CoA synthetases.
(3 diff isozymes that are specific for short, intermediate and long chain FA exist).

2. CARNITINE CYCLE
The 2nd step is formation of acyl-carnitine by the Carnitine acyltransferase I in the
outer mito membrane. The acyl-carnitine diffuses through to the intermembrane
space.
In the 3rd step, acyl gp from acyl-carnitine is transferred to CoA by the enzyme
Carnitine acyltransferase II in the inner mito membrane.
Importance of Carnitine shuttle:
This carnitine-mediated entry process is the rate limiting step for FA oxidation and is also a regulation point.
Malonyl CoA normally inhibits Carnitine acyltransferase I enzyme

3. FATTY ACID OXIDATION There are basically 4 main rxns Dehydrogenation
Hydration
Thiolysis
The acetyl CoA formed can be oxidized via the TCA cycle.

4. OXIDATION – UNSATURATED FATTY ACID
Two additional enzymes are required
Enoyl-CoA isomerase
Enoyl-CoA reductase

5. KETONE BODIES - FORMATION
Formed even under normal conditions (from acetyl CoA not oxidized by TCA cycle).
Includes acetone, acetoacetate and β-hydroxybutyrate.
They are transported to extrahepatic tissues as fuel, converted to acetyl coA & oxidized by TCA cycle.
But, in uncontrolled diabetes or severe starvation, an over production of ketone bodies occur leading to acidosis or ketosis.
Mechanism: During starvation the body tries to form Glc via gluconeogenesis. This depletes TCA cycle intermediates stopping acetyl CoA oxidation. Likewise, during uncontrolled diabetes (due to insulin deficiency) cells can’t take up glc from blood either to breakdown or convert to fat. Malonyl CoA conc decreases, inhibition of CAT-I is relieved, FA enter into mito & get degraded to acetyl CoA which can’t pass thro TCA cycle because they have been diverted to gluconeogenesis. This excess acetyl CoA results in ketone body formation.