BGZ2004
Problem 5 Fat metabolism
Silverthorn
Fed state metabolism à fats store energy
Most ingested fats are assembled inside intestinal epithelial cells into lipoprotein
and lipid complexes called chylomicrons. They leave the intestine and enter the
venous circulation via the lymphatic vessels. (22.6)
Chylomicrons consist of cholesterol, triglycerides, phospholipids and lipid-binding
proteins called apoproteins. Once these lipid complexes begin to circulate
through the blood, the enzyme lipoprotein lipase bound to the epithelium of
muscles and adipose tissue, converts the triglycerides to free fatty acids and
glycerol.
These molecules may be used for energy or reassembled into triglycerides for
storage in adipose tissue.
Chylomicron remnants that remain in the circulation are taken up and
metabolized in the liver. Cholesterol from the remnants joins the livers pool of
lipids. If cholesterol is in excess, some may be converted into bile salts and
excreted into bile. The remaining cholesterol is added to newly synthesized
cholesterol and fatty acids, and packaged into lipoprotein complexes for secretion
into the blood.
The lipoprotein complexes that re-enter the blood contain triglycerides,
phospholipids, cholesterol and apoproteins. The more protein is in a complex, the
,heavier it is. Plasma lipoprotein varies from VLDL to HDL protein. Because lipids
and proteins are combined, cholesterol becomes more soluble in plasma, but the
complexes can hardly diffuse through cell membranes. They must be brought into
cells by receptor-mediated endocytosis. The apoproteins in the complexes have
specific membrane receptors in different tissues.
Most lipoprotein in the blood is LDL. LDL-C complexes contain apoprotein B
(apoB), which combines with receptors that bring LDL-C into most cells of the
body. The second most common lipoprotein in the blood is high density
lipoprotein-cholesterol (HDL-C). This is the health cholesterol, it is involved in
transport of cholesterol out of the plasma. HDL-C contains apoprotein A (apo A),
which facilitates cholesterol uptake by the liver and other tissues.
Lipid synthesis- fed state
If diet is insufficient, the body can produce cholesterol. The body can make
cholesterol from acetyl CoA.
During the fed state, other fats (such as phospholipids) can be made from non-
lipid precursors. Enzymes in the smooth ER and cytosol of cells are responsible
for this.
Triglyceride synthesis from excess glucose and protein is important for the fed
state metabolism.
Glycerol can be made from glucose or from glycolysis intermediates. Fatty acids
are made from acetyl-CoA (from glycolysis), when fatty acid synthetaqse links the
2-carbon acyl groups into carbon chains. This requires hydrogen and high energy
electrons from NADPH. In the ER the combination of glycerol and fatty acids into
triglycerides is made.
Fasted state – lipids store more energy than glucose or protein
Lipids are the primary fuel storage molecule of the body because they have a
higher energy content than carbos or proteins. Lipases break down triglycerides
into glycerol and fatty acids during fasting through a series of reactions:
lipolysis. Glycerol that comes from this pathway can be used for glycolysis.
(page 794 of Silverthorn).
- Triglyceride is digested by lipases into glycerol and 3 fatty acids
o Glycerol can go to glycolysis
- Fatty acids have to move into the mitochondrial matrix to be turned into
ATP.
- As 2-carbon units are chopped of at the end of the chain, one at a time,
they are disassembled: beta-oxidation.
- In most cells, the 2 carbon units are converted into acetyl CoA, this goes
directly into the citric acid cycle. Many acetyl-CoA molecules can be
produced from 1 single fatty acid.
In the fasted state, adipose tissue releases fatty acids and glycerol into the blood.
Glycerol vcan be converted into glucose by gluconeogenesis in the liver. The fatty
acids are used for energy production.
In the liver, if fatty acid breakdown produces more acetyl CoA than the citric acid
cycle can metabolize it, the excess acyl units will become ketone bodies. They
can create a state of ketosis in the blood.
When mostly fat is consumed, metabolism switches to beta oxidation of fats and
production of ketone bodies. When these people lose wiehgt, its due to glycogen
breakdown and water loss, not body fat reduction.
, 1. What are chylomicrons (lipoproteins)?
Fat = triacylglycerols/ triglycerids. They are transported in lipoproteins.
- Exogenous (dietary) TAG is transported in chylomicrons
- Endogenous TAG transported in VLDL
The major energy store of the body is triacylgycerol, a hydrophobic compound.
The transport of triacylglycerol and cholesterol occurs in specialized
macromolecular structures known as lipoproteins. The metabolism of these two
lipids in the plasma is closely interrelated.
The lipoproteins have a lipid, highly hydrophobic interior (core) and a relatively
hydrophilic outer surface. All lipoproteins carry all types of lipid, but in different
quantities and relative proportions. Figure 10.1 Frayn
A lipoprotein particle consists of a core of triacylglycerol and cholesterol ester,
with an pouter surface monolayer of phospholipid and free cholesterol. The
phospholipids and cholesterol stabilize the particle in the aqueous environment of
the plasma: their hydrophilic heads face outwards, ang their hydrophobic tails are
into the particle.
Each lipoprotein particle has associated with one or more protein molecules, the
apolipoproteins. These have hydrophobic domains, which go into the core and
anchor the protein to the particle, and also hydrophilic domains that are exposed
at the surface.
The lipoproteins consist of a heterogenous group of particles with different lipid
and protein composition.
- Chylomicrons particles
- VLDL particles
Relatively rich in triacylglycerol and are mainly concerned with delivery of
triacylglycerol to tissues.
The smaller HDL and LDL particles are more involved with transport of cholesterol
to and from cells.
Density increases, size decreases.
Major lipids Major
apolipoproteins
Chylomicrons Dietary TAG B48, AI, AIV, C, E,
(lowest density)
VLDL (very low Endogenous TAG B100, C, E
density) (from liver)
LDL(low density) Cholesterol and B100
cholesteryl ester
HDL (high density) Cholesteryl ester AI, AII, C, E
This density is proportional to protein content and inversely proportional to TAG
content.
Problem 5 Fat metabolism
Silverthorn
Fed state metabolism à fats store energy
Most ingested fats are assembled inside intestinal epithelial cells into lipoprotein
and lipid complexes called chylomicrons. They leave the intestine and enter the
venous circulation via the lymphatic vessels. (22.6)
Chylomicrons consist of cholesterol, triglycerides, phospholipids and lipid-binding
proteins called apoproteins. Once these lipid complexes begin to circulate
through the blood, the enzyme lipoprotein lipase bound to the epithelium of
muscles and adipose tissue, converts the triglycerides to free fatty acids and
glycerol.
These molecules may be used for energy or reassembled into triglycerides for
storage in adipose tissue.
Chylomicron remnants that remain in the circulation are taken up and
metabolized in the liver. Cholesterol from the remnants joins the livers pool of
lipids. If cholesterol is in excess, some may be converted into bile salts and
excreted into bile. The remaining cholesterol is added to newly synthesized
cholesterol and fatty acids, and packaged into lipoprotein complexes for secretion
into the blood.
The lipoprotein complexes that re-enter the blood contain triglycerides,
phospholipids, cholesterol and apoproteins. The more protein is in a complex, the
,heavier it is. Plasma lipoprotein varies from VLDL to HDL protein. Because lipids
and proteins are combined, cholesterol becomes more soluble in plasma, but the
complexes can hardly diffuse through cell membranes. They must be brought into
cells by receptor-mediated endocytosis. The apoproteins in the complexes have
specific membrane receptors in different tissues.
Most lipoprotein in the blood is LDL. LDL-C complexes contain apoprotein B
(apoB), which combines with receptors that bring LDL-C into most cells of the
body. The second most common lipoprotein in the blood is high density
lipoprotein-cholesterol (HDL-C). This is the health cholesterol, it is involved in
transport of cholesterol out of the plasma. HDL-C contains apoprotein A (apo A),
which facilitates cholesterol uptake by the liver and other tissues.
Lipid synthesis- fed state
If diet is insufficient, the body can produce cholesterol. The body can make
cholesterol from acetyl CoA.
During the fed state, other fats (such as phospholipids) can be made from non-
lipid precursors. Enzymes in the smooth ER and cytosol of cells are responsible
for this.
Triglyceride synthesis from excess glucose and protein is important for the fed
state metabolism.
Glycerol can be made from glucose or from glycolysis intermediates. Fatty acids
are made from acetyl-CoA (from glycolysis), when fatty acid synthetaqse links the
2-carbon acyl groups into carbon chains. This requires hydrogen and high energy
electrons from NADPH. In the ER the combination of glycerol and fatty acids into
triglycerides is made.
Fasted state – lipids store more energy than glucose or protein
Lipids are the primary fuel storage molecule of the body because they have a
higher energy content than carbos or proteins. Lipases break down triglycerides
into glycerol and fatty acids during fasting through a series of reactions:
lipolysis. Glycerol that comes from this pathway can be used for glycolysis.
(page 794 of Silverthorn).
- Triglyceride is digested by lipases into glycerol and 3 fatty acids
o Glycerol can go to glycolysis
- Fatty acids have to move into the mitochondrial matrix to be turned into
ATP.
- As 2-carbon units are chopped of at the end of the chain, one at a time,
they are disassembled: beta-oxidation.
- In most cells, the 2 carbon units are converted into acetyl CoA, this goes
directly into the citric acid cycle. Many acetyl-CoA molecules can be
produced from 1 single fatty acid.
In the fasted state, adipose tissue releases fatty acids and glycerol into the blood.
Glycerol vcan be converted into glucose by gluconeogenesis in the liver. The fatty
acids are used for energy production.
In the liver, if fatty acid breakdown produces more acetyl CoA than the citric acid
cycle can metabolize it, the excess acyl units will become ketone bodies. They
can create a state of ketosis in the blood.
When mostly fat is consumed, metabolism switches to beta oxidation of fats and
production of ketone bodies. When these people lose wiehgt, its due to glycogen
breakdown and water loss, not body fat reduction.
, 1. What are chylomicrons (lipoproteins)?
Fat = triacylglycerols/ triglycerids. They are transported in lipoproteins.
- Exogenous (dietary) TAG is transported in chylomicrons
- Endogenous TAG transported in VLDL
The major energy store of the body is triacylgycerol, a hydrophobic compound.
The transport of triacylglycerol and cholesterol occurs in specialized
macromolecular structures known as lipoproteins. The metabolism of these two
lipids in the plasma is closely interrelated.
The lipoproteins have a lipid, highly hydrophobic interior (core) and a relatively
hydrophilic outer surface. All lipoproteins carry all types of lipid, but in different
quantities and relative proportions. Figure 10.1 Frayn
A lipoprotein particle consists of a core of triacylglycerol and cholesterol ester,
with an pouter surface monolayer of phospholipid and free cholesterol. The
phospholipids and cholesterol stabilize the particle in the aqueous environment of
the plasma: their hydrophilic heads face outwards, ang their hydrophobic tails are
into the particle.
Each lipoprotein particle has associated with one or more protein molecules, the
apolipoproteins. These have hydrophobic domains, which go into the core and
anchor the protein to the particle, and also hydrophilic domains that are exposed
at the surface.
The lipoproteins consist of a heterogenous group of particles with different lipid
and protein composition.
- Chylomicrons particles
- VLDL particles
Relatively rich in triacylglycerol and are mainly concerned with delivery of
triacylglycerol to tissues.
The smaller HDL and LDL particles are more involved with transport of cholesterol
to and from cells.
Density increases, size decreases.
Major lipids Major
apolipoproteins
Chylomicrons Dietary TAG B48, AI, AIV, C, E,
(lowest density)
VLDL (very low Endogenous TAG B100, C, E
density) (from liver)
LDL(low density) Cholesterol and B100
cholesteryl ester
HDL (high density) Cholesteryl ester AI, AII, C, E
This density is proportional to protein content and inversely proportional to TAG
content.
