Lipid digestions,absorbtin transport will be covered separately.

Lipases hydrolyze triacylglycerols, releasing one fatty acid at a time, producing

diacylglycerols, and eventually glycerol. .
Glycerol arising from hydrolysis of triacylglycerols is converted to the Glycolysis
intermediate dihydroxyacetone phosphate, by reactions catalyzed by:
(1) Glycerol Kinase
(2) Glycerol Phosphate Dehydrogenase.

Free fatty acids, which in solution have detergent properties, are transported in the blood
bound to albumin, a serum protein produced by the liver.
Several proteins have been identified that facilitate transport of long chain fatty acids into
cells, including the plasma membrane protein CD36.

Fatty acid activation:

Fatty acids must be esterified to Coenzyme A before they can undergo oxidative degradation,
be utilized for synthesis of complex lipids (e.g., triacylglycerols or membrane lipids), or be
attached to proteins as lipid anchors.

Acyl-CoA Synthases (Thiokinases), associated with endoplasmic reticulum membranes and

the outer mitochondrial membrane, catalyze activation of long chain fatty acids, esterifying
them to coenzyme A, as shown at right. This process is ATP-dependent, and occurs in 2
steps. There are different Acyl-CoA Synthases for fatty acids of different chain lengths.

Exergonic hydrolysis of PPi (P~P), catalyzed by Pyrophosphatase, makes the coupled

reaction spontaneous. Overall, two ~P bonds of ATP are cleaved during fatty acid activation.
The acyl-coenzyme A product includes one "high energy" thioester linkage.

Summary of fatty acid activation:

• fatty acid + ATP  acyl-adenylate + PPi

PPi  2 Pi
• acyladenylate + HS-CoA  acyl-CoA + AMP

Overall: fatty acid + ATP + HS-CoA  acyl-CoA + AMP + 2 Pi

Fatty acids are degraded in the mitochondrial matrix via the β -Oxidation Pathway. For most
steps of the pathway there are multiple enzymes specific for particular fatty acid chain
lengths. Many of the constituent enzymes are soluble proteins located in the mitochondrial
matrix. But enzymes specific for very long chain fatty acids are associated with the inner
mitochondrial membrane, facing the matrix.

Fatty acyl-CoA formed outside the mitochondria can pass through the outer mitochondrial
membrane, which contains large VDAC channels, but cannot penetrate the mitochondrial
inner membrane.
Transfer of the fatty acid moiety across the mitochondrial inner membrane involves carnitine.

Carnitine Palmitoyl Transferases catalyze transfer of a fatty acid between the thiol of
Coenzyme A and the hydroxyl on carnitine.

Carnitine-mediated transfer of the fatty acyl moiety into the mitochondrial matrix is a 3-step
process, as presented below.
1. Carnitine Palmitoyl Transferase I, an enzyme associated with the cytosolic surface of the
outer mitochondrial membrane, catalyzes transfer of a fatty acid from ester linkage with the
thiol of coenzyme A to the hydroxyl on carnitine.

2. Carnitine Acyltransferase, an antiporter in the inner mitochondrial membrane, mediates

transmembrane exchange of fatty acyl-carnitine for carnitine.

3. Within the mitochondrial matrix (or associated with the matrix surface of the inner
mitochondrial membrane, Carnitine Palmitoyl Transferase II catalyzes transfer of the fatty
acid from carnitine to coenzyme A. (Carnitine exits the matrix in step 2.) The fatty acid is
now esterified to coenzyme A within the mitochondrial matrix.