FATTY ACID OXIDATION Occurs inside mitochondria Activation of

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

CARNITINE CYCLE • The 2 nd 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 3 rd step, acyl gp from acyl-carnitine is transferred to Co. A 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 Co. A normally inhibits Carnitine acyltransferase I enzyme

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

OXIDATION – UNSATURATED FATTY ACID Two additional enzymes are required 1. Enoyl-Co. A isomerase 2. Enoyl-Co. A reductase

KETONE BODIES - FORMATION • Formed even under normal conditions (from acetyl Co. A not oxidized by TCA cycle). • Includes acetone, acetoacetate and β-hydroxybutyrate. • They are transported to extrahepatic tissues as fuel, converted to acetyl co. A & 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 Co. A 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 Co. A conc decreases, inhibition of CAT-I is relieved, FA enter into mito & get degraded to acetyl Co. A which can’t pass thro TCA cycle because they have been diverted to gluconeogenesis. This excess acetyl Co. A results in ketone body formation.