2.3 fatty acid metabolism + beta oxidation

Short and medium-chain fatty acids diffuse freely into the cytosol and mitochondria of cells.

Long-chain fatty acids must undergo protein-mediated transport across the cell membrane into the cytosol via

fatty acid translocase (FAT) or fatty acid-binding protein (FABP).

Acyl-CoA synthase then converts the fatty acids to fatty acyl-CoA

. The fatty acyl-CoA must now be transported into the mitochondria through the outer mitochondrial membrane

and is done so by carnitine palmitoyltransferase-I (CPT-I) where it becomes fatty acyl-carnitine.

The fatty acyl-carnitine is then transported across the inner membrane into the mitochondrial matrix by carnitine acyl-translocase (CAT)

and converted back to fatty acyl-CoA by palmitoyltransferase-II (CPT-II) where it is now ready for oxidation.

Beta oxidation

degradation of fatty acids by removing two carbons at a time

It is the primary pathway for catabolism of fatty acids

nd takes place in the mitochondrial matrix of tissues such as the liver, muscle, and adipose

Two-carbon fragments are successively removed from the carboxyl end of the fatty acyl-CoA, producing NADH, FADH, and Acetyl CoA,

which is used in the TCA cycle to make ATP.

Fatty acids with odd numbers of carbon ultimately yield one mole of propionyl-CoA,

which is converted to succinyl CoA so that it is usable in the TCA cycle.

Beta oxidation is also important as the primary regulator of movement through the pyruvate dehydrogenase (PDH) complex.

When rates of fatty acid oxidation are high, PDH activity decreases, which limits glycolysis,

which is significant because patients with a deficiency in fatty acid oxidation have a compensatory increase in glucose oxidation and impaired gluconeogenesis.