Lipid Metabolism

Metabolism of
Dietary Lipids
energy
hydrophobic barrier

fat-
soluble vitamins coenzyme functions
steroid hormones
DIGESTION, ABSORPTION, SECRETION, AND
UTILIZATION OF DIETARY LIPIDS

81 g, of which more than 90%

is normally triacylglycerol

cholesterol, cholesteryl esters,

phospholipids, and unesterified (“free”) fatty
acids
 . Processing of dietary lipid in the stomach

begins in the stomach acids stable lipase

(lingual lipase) that originates from glands at the back of the tongue

separate gastric lipase, secreted by the

gastric mucosa.
• 1. Cystic fibrosis (CF):
Northern
European ancestry,
mutations to the gene for the CF
transmembrane conductance regulator (CFTR) protein chloride
channel on epithelium.
decreased secretion of chloride and increased
reabsorption of sodium and water
decreased hydration results in thickened secretions
pancreatic enzymes are not able to reach the intestin

replacement of these enzymes and supplementation with fat-

soluble vitamins.
• B. Emulsification of dietary lipid in the small intestine.

duodenum
increases the surface area of the hydrophobic lipid droplets so
that the digestive enzymes

detergent properties of the bile salts, and mechanical mixing due

to peristalsis.
• Bile salts, made in the liver and stored in the gallbladder, are derivatives of
cholesterol
• C. Degradation of dietary lipids by pancreatic enzymes

• 1. TAG degradation: too large to be taken up efficiently

an
esterase, pancreatic lipase, at
carbons 1 and 3 2-
monoacylglycerol and free fatty acids.

• A second protein, colipase pancreas lipase at a

ratio of 1:1 Colipase restores
activity to lipase
• 2. Cholesteryl ester degradation:

• Cholesteryl esters are hydrolyzed by pancreatic cholesteryl ester

hydrolase produces cholesterol plus
free fatty acids.
 . Phospholipid degradation:
• Pancreatic juice is rich in the proenzyme of phospholipase A2
removes one fatty acid from carbon 2 of a
phospholipid, leaving a lysophospholipid.
phosphatidylcholine becomes lysophosphatidylcholine.
The remaining fatty acid at carbon 1 can be removed by
lysophospholipase, leaving a glycerylphosphoryl
• 4. Control of lipid digestion:

• Cells in the mucosa of the lower duodenum and jejunum produce a small peptide
hormone, cholecystokinin (CCK

• CCK acts on the gallbladder (causing it to contract and release bile—a mixture of
bile salts, phospholipids, and free cholesterol

• It also decreases gastric motility, resulting in a slower release of gastric contents

into the small intestine .
secretin
Secretin causes the
pancreas and the liver to release a solution rich in bicarbonate that helps neutralize
the pH of the intestinal contents, bringing them to the appropriate pH for digestive
activity by pancreatic enzymes.
• D. Absorption of lipids by intestinal mucosal cells (enterocytes)

• Free fatty acids, free cholesterol, and 2-monoacylglycerol are the primary
products of lipid digestion in the jejunum
mixed micelles

Mixed micelles
are, therefore, soluble in the aqueous environment of the intestinal lumen

facilitates the transport of the

hydrophobic lipids through the unstirred water layer to the brush border
• E. Resynthesis of TAG and cholesteryl esters
• The mixture of lipids absorbed by the enterocytes migrates to the
endoplasmic reticulum where biosynthesis of complex lipids takes place
• Fatty acids are first converted into their activated form by fatty acyl-CoA
synthetase
converted to TAGs by
the enzyme complex, TAG synthase.

acyl CoA:monoacylglycerol acyltrans-ferase and acyl

CoA:diacylglycerol acyltransferase
• Lysophospho - lipids are reacylated to form phospholipids by a family of
acyltransferases cholesterol is esterified to a fatty acid primarily by
acyl CoA:cholesterol acyltransferase
Dietary Fats Are Absorbed in the Small
Intestine
insoluble
macroscopic fat particles to finely dispersed microscopic micelles
solubilization is carried out by bile salts taurocholic
acid, which are synthesized from cholesterol in the liver, stored in
the gallbladder, and released into the small intestine after ingestion
of a fatty meal.
• Bile salts are amphipathic compounds that act as biological
detergents, converting dietary fats
 fraction of lipid molecules
accessible to the action of water-soluble lipases
lipase action converts triacylglycerols to monoacylglycerols
(monoglycerides) and diacylglycerols (diglycerides), free fatty acids,
and glycerol
diffuse into the epithelial

reconverted to triacylglycerols packaged with dietary cholesterol

and specific proteins into lipoprotein aggregates called chylomicrons
 protein moieties of lipoproteins

apolipoprotein C-II (apoC-II 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, activated by apoC-II, hydrolyzes triacylglycerols
to fatty acids and glycerol (step 6 ), which are taken up by cells in
the target tissues

• In muscle, the fatty acids are oxidized for energy; in adipose tissue,
they are reesterified for storage as triacylglycerols
 remnants of chylomicrons depleted of most of their
triacylglycerols but still containing cholesterol and apolipoproteins,
travel in the blood to the liver

• Triacylglycerols that enter the liver

the liver converts them to triacylglycerols

VLDLs
VLDLs are transported in the blood to adipose tissues, where the
triacylglycerols are removed and stored in lipid droplets within
adipocytes
• Triacylglycerols sequestered in the
interior (yellow) make up more
than 80% of the mass
apolipoproteins that
protrude from the surface (B-48, C-
III, C-II) act as signals in the uptake
and metabolism of chylomicron
contents
 contained in chylomicrons is broken down primarily in the
capillaries of skeletal muscle and adipose tissues

degraded to free fatty acids and glycerol

by lipoprotein lipase. adipocytes
and muscle cells
 . Fate of free fatty acids:
either directly enter adjacent muscle cells or adipocytes
transported in the blood

• 2. Fate of glycerol
by the liver to produce glycerol 3-phosphate
glycolysis or gluconeogenesis
• 3. Fate of the remaining chylomicron components
the chylomicron remnants
(which contain cholesteryl esters, phospholipids, apolipoproteins,
fat-soluble vitamins, and some TAG) bind to receptors on the liver
and are then endocytosed.
hydrolyzed to their component

recycled