Digestion, mobilization and

transport of fatty acids

BY GROUP TWO
 Sources of fatty acids

 Cells obtain fatty acid fuels from three sources;

 Fats consumed in diet
 Fats stored in cells as lipid droplets
 Fats synthesized in one organ for export to another
vertebrates for example obtain fats in their diet, mobilize fats stored in specialized tissue
i.e. adipose tissue (consists of cells known as adipocytes) and in the liver excess carbohydrate
into fat for export to other tissues
Absorption and transport of fats

 In vertebrates, before ingested triacylglycerols can be absorbed through the intestinal

wall, they are first converted from insoluble macroscopic fat particles to finely dispersed
microscopic micelles.
 This solubilization is carried out by bile salts , synthesized from cholesterol in the liver,
stored in the gallbladder, and released into the small intestines after ingestion of a fatty
meal.
Absorption and transport of fatty acids

 Bile salts act as biological detergents, they convert dietary fats into mixed micelles of bile
salts and triacylglycerols.
 Micelle formation greatly increases the fraction of lipid molecules accessible to the of
water soluble lipases in the intestine, and lipase action converts triacylglycerols to
monoacylglycerols, diacylglycerols, fatty acids and glycerol.
 These products of lipase action diffuse into the epithelial cells lining the intestinal surface
(intestinal mucosa).
 In the intestinal mucosa they are reconverted to triacylglycerols and packaged with
dietary cholesterol and specific proteins into lipoprotein aggregate called chylomicrons.
Absorption and transport of fatty acids

 These chylomicrons move from the intestinal mucosa into the lymphatic system, and then
enter the blood which carries them to muscle and adipose tissue.
 In the capillaries of these tissues, the extracellular enzyme lipoprotein lipase, hydrolyses
triacylglycerols to fatty acids and glycerol.
 Fatty acids and glycerol are taken up by specific transporters in the plasma membrane to
target tissue.
 In muscle, the fatty acids are oxidized for energy, in adipose tissue they are re-esterified
for storage as triacylglycerols.
Processing of dietary lipids in vertebrates
Molecular structure of chylomicrons
Fate of glycerol

 About 95%of the biologically available energy of triacylglycerol is in the form of their
three long chain fatty acids and only 5% is contributed by glycerol.
 The glycerol released by lipase enzyme is phosphorylated by glycerol kinase, and the
resulting glycerol 3-phosphate is oxidized to dihydroxyacetone phosphate.
 The glycolytic enzyme triose phosphate isomerase converts it to glyceraldehyde 3-
phosphate(glycolate pathway), which is oxidized via glycolysis
Fate of glycerol
Mobilization of fatty acids stored in the
adipose tissue

 Released of glucagon (due to low glucose levels) binds to its receptors in the adipose
membrane.
 This stimulates adenyl cyclase via a G-protein to produce cAMP
 This activates PKA which phosphorylates the hormone sensitive lipase (HSL) and
perilipin molecule on the surface of the lipid droplet
 Phosphorylation of perilipin causes dissociation of the protein CGI-58 from perilipin
 CGI-58 then recruits adipose triacylglycerol lipase (ATGL) to the droplet surface and
stimulates its activity
Mobilization of fatty acids stored in the
adipose tissue

 Active ATGL converts triacylglycerol to diacylglycerol

 The phosphorylated perilipin associates with phosphorylated HLS allowing it to access
the surface where it converts diacylglycerol to monoacylglycerol.
 Fatty acids leave the adipocyte and are transported in blood bound to serum albumin.
 They are then released from albumin and enter a myocyte via a specific fatty acid
transporter
 In the myocyte, fatty acids are oxidized to CO2 and energy of oxidation is conserved in
ATP
mobilization of fatty acids stored in the
adipose tissue
Activation and transportation of fatty acids

 Enzyme of fatty acid oxidation in animals is found in the mitochondria

 <12C enter the mitochondria without the help of membrane transporters.
 >14C cannot pass directly through the mitochondrial membrane; they must first undergo
three enzymatic reaction of the carnitine shuttle.
 The first reaction is catalyzed by a family of isozymes present in the outer mitochondrial
membrane, the acyl-CoA synthetases, which promote the general reaction;
Activation and transport of fatty acids

 Acyl-CoA synthetase catalyses the formation of thioester linkage between the fatty acid
carboxyl group and thiol group of coenzyme A to yield the fatty acyl-CoA coupled to the
cleavage of ATP to AMP and PPi
 Reaction involves a fatty acyl adenylate intermediate
 Formation of a fatty acyl-CoA is made more favorable by the hydrolysis of two high
energy bonds in ATP
 PPi formed is immediately hydrolyzed by inorganic phosphatase pulling the reaction in
the direction of fatty acyl-CoA formation.
Activation and transport of fatty acids

 Fatty acyl-CoA destined for mitochondrial oxidation are attached to the hydroxyl group of
carnitine to form fatty acyl-carnitine.
 This catalyzed by carnitine transferase 1 in the outer membrane.
 The fatty acyl- carnitine enters the matrix by passive transport through the carnitine
cotransporter on the inner membrane.
 The fatty acyl group is enzymatically transferred from carnitine to intramitocondrial
coenzyme A by carnitine acyl transferase11
 The released carnitine re-enters the intermembrane space via carnitine transporter
Activation and transport of amino acids
General structure of a lipoprotein