Metabolism of Lipids

Metabolism of lipids
Dr.Rijha Ahmed
Biochemistry department KEMU
LEARNING OBJECTIVES
• Digestion, Mobilization, and Transport of Fats
• How Dietary Fats Are Absorbed in the Small
Intestine?
• Hormones Trigger Mobilization of Stored
Triacylglycerol
• Lipid malabsorption
• Fate of FFAs,glycerol and remaining
chylomicrons components
• they also provide the hydrophobic barrier that
permits partitioning of the aqueous contents
of cells and subcellular structures.
• Lipids serve additional functions in the body
(for example, some fat-soluble vitamins have
regulatory or coenzyme functions, and the
prostaglandins and steroid hormones play
major roles in the control of the body’s
homeostasis
• The average daily intake of lipids by U.S. adults
is about 81 g,
• 90% is normally Triacylglycerol ([TAG] The
remainder of the dietary lipids consists
primarily of cholesterol, cholesteryl esters,
phospholipids, and unesterified (“free”) fatty
acids.
• Triacylglycerol (TAG) consists of three fatty acids
esterified to a glycerol backbone.
Structures of some common classes of lipids. Hydrophobic
portions of the molecules are shown in orange
Digestion, Mobilization, and
Transport of Fats
• Cells can obtain fatty acid fuels from three
sources:
• Fats consumed in the diet,
• fats stored in cells as lipid droplets, and
• fats synthesized in one organ (liver from excess
dietary CHO )for export to another.
• On average, 40% or more of the daily energy
requirement of humans --- dietary
Triacylglycerol(triglycerides,natural fats)
Processing of dietary lipid in the stomach
• lingual lipase
• originates from glands at the back of the tongue. TAG molecules,
particularly those containing fatty acids of short- or medium-chain
length (fewer than 12 carbons such as are found in milk fat), are
the primary target of this enzyme.
• gastric lipase, secreted by the gastric mucosa.
• Both enzymes are acid stable, optimumal pH of pH 4 to pH 6.
These “acid lipases” play a particularly important role in lipid
digestion in
 neonates, for whom milk fat is the primary source of calories.
 individuals with pancreatic insufficiency such as those with cystic
fibrosis (CF).
Cystic fibrosis
• CF is the most common lethal genetic disease in Caucasians of Northern European
ancestry.
• prevalence 1:3,300 births in the United States.
• autosomal recessive disorder
• mutations to the gene for the CF transmembrane conductance regulator (CFTR) protein.
• CFTR functions as a chloride channel on epithelium in the pancreas, lungs, testes, and
sweat glands.
• Defective CFTR results in decreased secretion of chloride and increased uptake of sodium
and water.
• In the pancreas, the depletion of water on the cell surface → thickened secretions →
clog the pancreatic ducts → pancreatic insufficiency.
• Treatment includes replacement of these enzymes and supplementation with fat soluble
vitamins.
• [Note: CF also causes chronic lung infections with progressive pulmonary disease and
male infertility.]
Degradation of dietary lipids by pancreatic
enzymes
1.Triacylglycerol degradation:
• esterase, pancreatic lipase,
• colipase,
2. Cholesteryl ester degradation:
Most dietary cholesterol--- free(nonesterified) form,
10%–15% present in the esterified form.
pancreatic cholesteryl ester hydrolase .
3. Phospholipid degradation:
proenzyme of phospholipase A2,
Phospholipase A2 removes one fatty acid from carbon 2 of a
phospholipid --- lysophospholipid. The remaining fatty acid at carbon 1
can be removed by lysophospholipase, leaving a glycerylphosphoryl base.
Control of lipid digestion
• Cholecystokinin (CCK),
• Secretin
Dietary Fats Are Absorbed in the Small
Intestine
1.solubilization is carried out by bile salts, such as
taurocholic acid or glycocholic acid.
2.Lipases coverts TAGs to monoacylglycerol and
diacylglycerols
3.Diffussion thru epithelial cell lining the intestinal
surface
4.Reconversion to triacylglycerol and packaged with
dietary cholesterol and specific proteins into
lipoprotein aggregates called chylomicrons
Absorption of lipids by intestinal mucosal
cells, or enterocytes
• Free fatty acids, free cholesterol, and 2-monoacylglycerol
are the primary products of lipid digestion in the jejunum.
FFA ,bile salts and fat-soluble vitamins (A, D, E,
and K), form mixed micelles (that is, disc-shaped clusters
of a mixture of amphipathic lipids that coalesce with their
hydrophobic groups on the inside and their hydrophilic
groups on the outside.
soluble in the aqueous environment .
These particles approach the primary site of lipid
absorption, the brush border membrane of the enterocytes
Lipid malabsorption
• Lipid malabsorption, resulting in increased lipid

(including the fat-soluble vitamins and essential fatty
acids) in the feces, a condition known as steatorrhea.
• CF (causing poor digestion)
• short bowel syndrome (causing decreased
absorption).
• Short- and medium-chain length fatty acids to be
taken up by enterocytes without the aid of mixed
micelles
Causes of steatorrea
Resynthesis of triacylglycerols and cholesteryl esters
Intestine
• Apolipoproteins are lipid-binding proteins in
the blood, responsible for the transport of
triacylglycerols,phospholipids, cholesterol, and
cholesteryl esters between organs.
• Various combinations of lipid and protein
produce particles of different densities,
ranging from chylomicrons and verylow-
density lipoproteins (VLDL) to very-high-
density lipoproteins (VHDL)
Intestine
5.Chylomicrons, which contain apolipoprotein C-II
(apoC-II), move from the intestinal mucosa into
the lymphatic system, and then enter the blood,
which carries them to muscle and adipose tissue.
6. In the capillaries of these tissues, the
extracellular enzyme lipoprotein lipase,
activated by apoC-II, hydrolyzes triacylglycerols
to fatty acids and glycerol
7. taken up by cells in the target tissues
Mobilization of Dietary Fats
8.In muscle, the fatty acids are oxidized for energy;
• In adipose tissue, they are re-esterified for storage as
triacylglycerol.
 The remnants of chylomicrons, travel in the blood to
the liver
• Triacylglycerol that enter the liver by this route may be
1.oxidized to provide energy
2.To provide precursors for the synthesis of ketone
bodies.
Mobilization of Dietary Fats
• When the diet contains more fatty acids than are
needed immediately for fuel or as precursors,
• the liver converts them to triacylglycerols, which
are packaged with specific apolipoproteins into
VLDLs.
• The VLDLs are transported in the blood to
adipose tissues,
• where the triacylglycerols are removed and
stored in lipid droplets within adipocytes.
Hormones Trigger Mobilization
of Stored Triacylglycerols
• Neutral lipids are stored in adipocytes (and in
steroid synthesizing cells of the adrenal cortex,
ovary, and testes) ----- lipid droplets,
 core of sterol esters and triacylglycerols
 surrounded by a monolayer of phospholipids.
 The surface of these droplets is coated with
perilipins.
• When hormones signal the need for metabolic
energy,
• triacylglycerols stored in adipose tissue are
mobilized
• transported to tissues(skeletal muscle, heart,
and renal cortex) in which fatty acids can be
oxidized for energy production.
• Hormones epinephrine and glucagon, secreted in
response to low blood glucose levels,
• activate the enzyme adenylyl cyclase in the adipocyte
plasma membrane → intracellular second messenger
cyclic AMP → Cyclic AMP–dependent protein kinase
(PKA) Phosphorylates perilipin A,
• phosphorylated perilipin causes
• hormone-sensitive lipase in the cytosol to move to the
lipid droplet surface, where it can begin hydrolyzing
triacylglycerols to free fatty acids and glycerol.
 More than 50-fold increase in fat
mobilization triggered by epinephrine is due
primarily to perilipin phosphorylation.
 free fatty acids, FFA pass from the adipocyte
into the blood, where they bind to the blood
protein serum albumin.
 noncovalently binds as many as 10 fatty acids
per protein monomer.
• About 95% of the biologically available energy
of triacylglycerols
 resides in their three long-chain fatty acids;
 only 5% is contributed by the glycerol moiety.
Fate of glycerol
 The glycerol
• released by lipase action is
phosphorylated by glycerol
kinase ,
• Glycerol 3-phosphate is oxidized
to dihydroxyacetone phosphate.
• The glycolytic enzyme triose
phosphate isomerase converts
this compound to
glyceraldehyde 3-
phosphate,which is oxidized via
glycolysis.
Fate of FFA
• Directly enter adjacent muscles or adipocytes.
• Transported in blood in association with
albumin.
• Energy production by oxidation.
• Re esterified to TAGs in adipocytes.
Fate of the remaining chylomicron
components
• After most of the TAG has been removed,
• the chylomicron remnants (which contain cholesteryl esters,
phospholipids, apolipoproteins, fat-soluble vitamins, and a small amount
of TAG)
• bind to receptors on the liver (apolipoprotein E is the ligand)
• endocytosed.
• The intracellular remnants are hydrolyzed to their component parts.
• Cholesterol and the nitrogenous bases of phospholipids (for example,
choline) can be recycled by the body.
• If removal of remnants by the liver is decreased due to impaired binding
to their receptor, they accumulate in the plasma. This is seen in the rare
type III hyperlipoproteinemia (also called familial
dysbetalipoproteinemia

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Metabolism of lipids

• Lipid malabsorption, resulting in increased lipid

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