Lipid Metabolizmasi

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Fat catabolism generation of energy by fatty
acid oxidation Fat (triacylglycerol) and Fatty
Acids 90 of dietary lipids are
tryacylglycerol, a hydrophobic, neutral molecule
made from reaction of OH group of glycerol and
COO- group of fatty acids. Fatty acids are made
up of a long hydrophobic hydrocarbon chain
(highly reduced) and a carboxylic acid polar
group. Different kinds of fatty acids play very
important structural (as major component of
membrane structures) and functional role. In
this part of discussion we will mainly focus of
the digestion, transport and catabolism of
triglycerides. Although other lipids like
cholesterol, sphingolipids are important too but
they will not be covered in this course. Sources
of Fat available for oxidation 1. Dietary fat,
2. Excess dietary fat stored in adipose tissue
and 3. Excess carbohydrate calories are
converted to FAT in liver and transported to
adipose tissues. Function -Stored fat acts as
major energy source when there is no carbohydrate
available, -it also serves as source for supply
of fatty acids required for important cellular
function provide insulation and complexion to body
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Michael Cooper Has cut his calorie intake to
nearly half of the daily requirement. He does not
have any fat storage, thus he faces the following
problems 1. Looks sick bad complexion or
look 2. He feels terribly cold even at 20 oC no
insulation. 3. Cannot afford to starve even for a
few days no fat store to sustain survival.
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Different kinds of lipids We will focus on
catabolism of storage lipids. Cholesterol
plays an important role in transport and
metabolism of lipids.
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Tri-acylglycerols (fat) molecules are highly
hydrophobic. After ingestion they are present in
the form of oil droplets. In order to get
digested and absorbed, they need to be emulsified
(partially solubilized. Liver produces bile
acids which are collected in gall bladder and
released into intestine, where they in
emulsification of fat. Bile acids are
amphipathic, detergent like molecules capable of
binding to hydrophobic as well as hydrophilic
molecules.
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Some important players involved in lipid
digestion and transport Bile Acids These are
amphiphathic (with polar and non-polar
structures) detergent like molecules synthesized
in liver. They help solubilize or emulsify the
triglycerides (fat) in the small
intestine. Pancreatic Lipases These are
pancreatic enzymes that catalyze the hydrolysis
of fat to release fatty acids and glycerol in
intestine. Bile acid and Fatty acid binding
proteins They facilitate absorption of lipids in
intestine. Intestinal Fatty acid binding proteins
(I-FABP) these proteins are present inside the
intestinal cells, they bind to fatty acids and
protect cells from the detergent like behavior of
fatty acids. Chylomicrons These are lipoprotein
granules containing specific lipoproteins,
dietary cholesterol, phospholipids and
triacylglycerol. These transport granules
transport cholesterol and lipids from intestine
to adipose tissues and liver via blood.
Lipoprotein lipase These enzymes are present in
the capillaries of the peripheral tissues. They
digest triglycerides into Fatty acid and
glycerol.
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Lipid Transport Chylomicrons transport
cholesterol and lipids from intestine to adipose
tissues and liver via blood. Very low density
lipoproteins (VLDL) are synthesized in liver and
transport endogenous triacylglycerol and
cholesterol from liver to adipose and muscle
tissue. Capilary lipoprotein lipases degrade VLDL
and fatty acid and glycerol are delivered to
adipocytes or muscle. After giving up their
triacylglycerols, the VLDL remnants appear in the
blood as Intermediate density lipoproteins (IDL)
and then as low density lipoproteins (LDL). IDL
and LDLs are taken back by liver by specific
receptor mediated endocytosis. High density
lipoproteins (HDL) are assembled from the
degradation products of other lipoproteins. HDLs
mop up excess cholesterol from other tissues and
deliver it to liver.
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• Utilization of stored fat
• Low blood glucose and energy need trigger the
  secretion of epinephrine and glucagon hormones
  
• Activation of adnylate cyclase
• Production of cAMP
• Activation of cAMP-dependent protein kinase
• Phosphorylation and activation of triacylglycerol
  lipase
• Release of fatty acids in blood and binding of
  fatty acids to serum albumin
• Transport of FA through serum albumin to the
  muscle tissues
• B-oxidation of FA to produce acetyl CoA.

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Catabolism of glycerol after lipase
reaction After the triacylglycerol (fat) is
digested by lipase, it releases fatty acids, and
glycerol. Glycerol can be converted to glycerol 3
phosphate and then to dihydroxy acetone phosphate
(DHAP). DHAP is converted to Glyceraldehyde 3 P
by triose phosphate isomerase (reaction 5)
which enters the GAPDH reaction (reaction 6)of
glycolysis directly.