CHE 350 Lecture Notes - Lecture 14: Transamination, Glycogenesis, Anabolism
Lipid Digestion, Absorption, Transportation
Triglycerides (triacylglycerols) constitute ~90% of dietary lipids and are the major
form of metabolic energy storage in humans
Fatty acids carry more energy per carbon because they are more reduced, carry
less water cause they're non polar
1/3 of our energy comes from dietary triglycerides, 80% of our energy needs of
heart and liver are met by oxidation of fatty acids.
oGrizzly bears rely exclusively on this. Camels store fat as sources of water
Fats -> CO2 + H2O + Energy
o4 pathways: fatty acid transport, b-oxidation, TCA cycle, electron transport
Fatty acid oxidation generates H2O, occurs when O2 is reduced by the final
reaction in the ETC, as well as the formation of H2O in oxidative phospho.
oReduction = gain e's, gain H's --> H2O from O2
Triacylglycerols are Digested before They Are Absorbed
Triglycerides are water insoluble, and digestive enzymes are water soluble =
triglyceride digestion takes place at lipid-water interface
Rate of digestion depends on surface area, movement, and emulsifying action of
bile acids (bile salts)
oBile = amphipathic detergent-like molecules that act to solubilize fat globs
by dispersing them into micelles
oCholesterol derivatives that are synthesized by the liver and secreted as
glycine or taurine conjugates into the gallbladder for storage
oFrom there they’re secreted into the small intestine where lipid digestion
and absorption mainly take place
Pancreatic lipase (triglyceride lipase) = catalyzes the hydrolysis of triglycerides at
their 1 and 3 positions to form 1,2-diacylglycerides and 2-acylglycerols, together
with the Na+ and K+ salts of fatty acids
oEnzyme activity increases when it hits lipid-water interface = interfacial
activation
oBinding to the interface reqs mixed micelles of bile acids and pancreatic
colipase
Intestinal mucosa = cells lining small intestine = absorb mix of fatty acids and
mono/di-acylglycerols produced by lipid digestion
Bile acids aid lipid digestion and are ESSENTIAL for the absorption of the
digestion products
The micelles formed by the bile acids take up the nonpolar lipid degradation
products so they can transport cross the aq. Boundary layer @ the intestinal wall
oPeople who have obstructed bile ducts don’t absorb the fats, they shit it out
Bile acids are req for the intestinal absorption of the lipid-soluble vitamins A, D,
E, K
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Inside intestinal cells, fatty acids from complexes w/ intestinal fatty acid-binding
protein (I-FABP) = a cytoplasmic protein that increases solubility of water
insoluble things and also protects the cell from their detergent like effects =
Lipids are Transported as Lipoproteins
Lipoproteins = globular micelle-like particles that consist of a nonpolar core of
triglycerides and cholesteryl esters surrounded by an amphiphilic coating of
protein, phospholipid, and cholesterol
oThere are 5 classes of lipoproteins (in human plasma)
Chylomicrons
VLDL (very low density lipoproteins)
IDL (intermediate density lipoproteins)
LDL (low density lipoproteins)
HDL (high density lipoproteins)
Intestinal mucosal cells convert fatty acids to triglycerides and package them,
along with dietary cholesterol into lipoproteins called chlomicrons
oReleased into intestinal lymph and are transported through the lymphatic
vessels before draining into the large veins
oBloodstream then delivers chylomicrons throughout the body
Chylomicrons are delipidated in the capillaries of peripheral tissues
oChylomicrons adhere to binding sites on inner surface (endothelium) of
capillaries in skeletal muscle and adipose tissue
oTheir component triglycerides and hydrolyzed thru the action of the
extracellular enzyme lipoprotein lipase
oThe tissues then take up the liberated monoacyglycerol and fatty acids
oChylomicrons shrink, turn into cholesterol-enriched chylomicron remnants,
which dissociate from the capillary endothelium and re-enter circulation to
be taken up by the liver
oChylomicrons deliver dietary triglycerides to muscle and adipose tissue,
and dietary cholesterol to the liver
VLDL, IDL, LDL = synthesized by the liver to transport endogenous (internally
produced) triglycerides and cholesterol from the liver to the tissues
HDL transports cholesterol and other lipids from the tissue back to the liver
VLDL are Gradually Degraded
oVLDL = transports endogenous triglycerides and cholesterol = also
degraded by lipoprotein lipase in capillaries of adipose tissue and muscle
oReleased fatty acids are taken up by cells and oxidized for energy or used to
resynth triglycerides
oGlycerol backbone of triglycerols is transported to the liver or kidneys and
converted to the glycolytic intermediate DHAP
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oOxidation (3 carbon unit) yields only a small fraction of the energy
available from oxidizing the 3 fatty acyl chains of a triglyceride
(triacylglycerol)
oAfter giving up triglycerides, VLDL remnants appear in the circulation first
as IDL and then as LDL
About 50% of the VLDL after degradation to IDL and LDL, are
taken up by the liver
Cells Take Up LDL by Receptor-Mediated Endocytosis
oCholesterol is acquired by taking up LDL or synthesizing it = LDL are rich
in cholesterol and cholesteryl esters
oTaking up LDL = receptor-mediated endocytosis of LDL
oLDL particles are taken up by LDL receptors (transmembrane
glycoproteins)
oLDL receptors cluster into clathrin-coated pits, which gather cell surface
receptors that are destined for endocytosis while excluding other cell-
surface proteins
oCoated pits = clathrin-coated vesicles in plasma membrane
oAfter getting rid of the clathrin coats, the vesicles fuse with others (called
endosomes)
pH is 5.0 so under these conditions the LDL particle dissociates
from receptor
receptors go back to cell surface, while endosome with its enclosed
LDL fuses w/ a lysosome
in lysosome, LDL cholesterol and fatty acids
HDL Transport Cholesterol from the Tissue to the Liver
oHDL is basically the opposite of LDL = they remove cholesterol from the
tissues
oHDL are assembled in the plasma from components obtained thru the
degradation of other lipoproteins
oCirculating HDL particle acquires cholesterol by extracting it from cell
surface membranes
oCholesterol is then converted to cholesteryl esters by HDL associated
enzyme lecithin-cholesterol acyl-transferace (LCAT)
oLiver is only organ capable of disposing of significant quantities of
cholesterol (by its conversion to bile acids)
About half of the VLDL after their degredation to IDL and LDL, are
taken up by the liver via LDL receptor mediated endocytosis
However, liver cells take up HDL by an entirely diff mechanism =
rather than being engulfed and degraded, an HDL particle binds to a
cell-surface receptor called SR-BI (scavenger receptor class B type
I) and selectively transfers its component lipids to the cell
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Document Summary
Triglycerides (triacylglycerols) constitute ~90% of dietary lipids and are the major form of metabolic energy storage in humans. Fatty acids carry more energy per carbon because they are more reduced, carry less water cause they"re non polar. 1/3 of our energy comes from dietary triglycerides, 80% of our energy needs of heart and liver are met by oxidation of fatty acids: grizzly bears rely exclusively on this. Fats -> co2 + h2o + energy: 4 pathways: fatty acid transport, b-oxidation, tca cycle, electron transport. Fatty acid oxidation generates h2o, occurs when o2 is reduced by the final reaction in the etc, as well as the formation of h2o in oxidative phospho: reduction = gain e"s, gain h"s --> h2o from o2. Triglycerides are water insoluble, and digestive enzymes are water soluble = triglyceride digestion takes place at lipid-water interface. Intestinal mucosa = cells lining small intestine = absorb mix of fatty acids and mono/di-acylglycerols produced by lipid digestion.
