2. Contents
12/30/2023 LIPID METABOLISM (Dr Akshay Shetty) 2
Objectives
Definition of
Lipids
Classification
of Lipids
Digestion of
lipids
Lipoproteins Apoproteins
Lipoprotein
pathways
3. 12/30/2023 LIPID METABOLISM (Dr Akshay Shetty) 3
Transport and
export of lipids
Role of HDL
Fatty acid
breakdown
pathway
Short chain and
long chain
breakdown
pathway
Summary References
4. Objectives
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By the end of the presentation the students must be
able to ---
ā¢ Define Lipids
ā¢ Classify Lipids
ā¢ Describe Digestion of lipids
ā¢ Illustrate Lipoproteins
ā¢ Illustrate Apoproteins
ā¢ Explain Lipoprotein pathways
ā¢ Discuss Transport and export of lipids
ā¢ Explain Role of HDL
ā¢ Explain Fatty acid breakdown pathway
ā¢ Describe Short chain and long chain breakdown pathway
5. Introduction
Lipids:
What are they?
We know them as āfatsā
Relatively water insoluble
Clinically important lipids:
ā¢ Cholesterol
ā¢ Triglyceride
ā¢ Phospholipids
ā¢ Glycolipid
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6. Definition
Biological molecules that are
insoluble in aqueous solutions
and soluble in organic solvents,
have some relation to fatty acids
as esters, and have potentiality
of utilization by living organisms
are classified as lipids.ā
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7. Functions
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Lipids are
essential for life
processes
Steroid hormone
precursor
Bile salt precursor;
aids digestion
āCell membrane
components
Provides energy,
fuel
Insulation,
protection of vital
organs
Provides maturity
to fetal lung as
pulmonary
surfactant
8. Bloorās Classification
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A. Simple lipid - ester of fatty acids with various alcohols
ā¢ 1. Natural fats and oils (triglycerides)
ā¢ 2. Waxes
ā¢ (a) True waxes: acetyl alcohol esters of fatty acids
ā¢ (b) Cholesterol esters
ā¢ (c) Vitamin A esters
ā¢ (d) Vitamin D esters
Compound lipid - esters of fatty acids with alcohol plus other groups
ā¢ 1. Phospholipids and spingomyelin: contains phosphoric acid and often a nitrogenous
base
ā¢ 2. Spingolipids (also include glycolipids and cerebrosides): contains amino alcohol
spingosine, carbohydrate, N-base; glycolipids contains no phosphate
ā¢ 3. Sulfolipids : contains sulfate group
ā¢ 4. Lipoproteins : lipids attached to plasma/other proteins
ā¢ 5. Lipopolysaccharides: lipids attached to polysaccharides
9. C. Derived lipids ā hydrolytic products of A & B with lipid characters
1. Saturated & unsaturated fatty acids
2. Monoglycerides and diglycerides
3. Alcohols (b-carotenoid ring, e.g., vitamin A, certain carotenoids)
D. Miscellaneous lipids
1. Aliphatic hydrocarbons: found in liver fat and certain
hydrocarbon found in beeswax and plant waxes
2. Carotenoids
3. Squalene : found in shark and mammalian liver and in
human sebam; an important intermediate in biosynthesis of
cholesterol
4. Vitamin E and K
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10. Digestion of lipids
ā¢ The majority of lipids in a normal diet are present in the
form of triacylglycerols.
ā¢ Digestion of these compounds begins in the stomach, which
contains acid-stable lipases that release some free fatty acids
from dietary triacylglycerols.
ā¢ However, the stomach is not capable of efficiently cleaving
triacylglycerols, because these hydrophobic molecules tend
to aggregate, and the lipases are only capable of hydrolyzing
the triacylglycerols at the surface of the aggregates.
ā¢ In addition, the stomach has a small surface area to volume
ratio, and therefore many of the triacylglycerols are not
accessible to the enzymes.
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11. Contā¦.
ā¢ The small intestine has mechanisms for emulsifying lipids.
ā¢ The process begins by dispersing the lipid aggregates
mechanically as a result of the muscles of the small intestine
forcing the partially digested material through the relatively
small spaces of the intestinal lumen.
ā¢ In addition, the intestine contains bile acids and bile salts
detergents that break up the lipid aggregates into smaller
micelles
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12. Contā¦
ā¢ Finally, the small intestine also contains a variety of digestive
enzymes produced in the pancreas. These enzymes include
pancreatic cholesteryl ester hydrolase
ā¢ Which releases free cholesterol from cholesteryl esters,
pancreatic lipase, which releases free fatty acids from the 1-
and 3-positions of triacylglycerols, and
severalphospholipases, which release free fatty acids from
phospholipids.
ā¢ The monoacylglycerols, partially hydrolyzed phospholipids,
and free fatty acids act asadditional detergents and assist in
further disrupting the larger lipid aggregates.
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13. Lipids ā¢ Actual lipid transport
involves specialized particles
combining the lipids with
specific proteins that allow
the control of lipid
movement.
Lipoproteins
ā¢ Lipoproteins consist of a
mixture of protein,
phospholipid, cholesterol,
and triacylglycerol. The
proportions of each vary
depending on the specific
type of particle.
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14. Lipoproteins are considered to
fall into four major classes:
1. Chylomicrons (the least dense form)
2. VLDL (very low density lipoproteins)
3. LDL (low density lipoproteins)
4. HDL (high density lipoproteins)
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18. Apolipoprotiens
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The proteins present in lipoproteins
are called apolipoproteins or simply
apoproteins.
(The prefix āapo-ā means without,
with apolipoprotein referring to the
protein without the lipid.)
The apoproteins play a major role in
the regulation of cellular interactions
with the lipoproteins
22. ā¢ Removal of fatty acids from chylomicrons and from
VLDL requires lipoprotein lipase, an enzyme located on
the capillary walls.
ā¢ Lipoprotein lipase requires Apo-CII and phospholipid as
activators; VLDL and chylomicrons have Apo-C-II,
allowing the lipoprotein lipase to hydrolyze the
triacylglycerols in these particles.
ā¢ Heart lipoprotein lipase has a lower Km for
triacylglycerol than does the adipose tissue isozyme; as
a result, the heart enzyme is always active, while the
rate of triacylglycerol cleavage by adipose tissue
depends on the level of substrate
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24. VLDL is synthesized and released by the liver. VLDL is used to
transport triacylglycerol from the liver to other tissues. As with
chylomicrons, triacylglycerols
from VLDL are hydrolyzed by lipoprotein lipase. Apo-C and B-100
are the major apoproteins in VLDL. As with chylomicrons, after
the majority of the triacylglycerols have been removed from the
VLDL, the Apo-C dissociates. The loss of the triacylglycerol
means that the remnants of the VLDL, called IDL
(intermediate density lipoprotein) have a higher density (due to
a higher protein to lipid ratio) and a higher ratio of cholesterol
to other lipids.
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26. 12/30/2023 LIPID METABOLISM (Dr Akshay Shetty) 26
ā¢ IDL is converted to LDL, largely by the liver, by removal of
additional triacylglycerol.
ā¢ In addition to its formation from VLDL, some LDL is
produced and released by the liver.
ā¢ LDL is a major transport form of cholesterol and cholesteryl
esters.
ā¢ The relative rates of VLDL and LDL release by the liver
depend on the availability of cholesterol. If the regulatory
pathways signal the liver to increase its cholesterol output,
then the liver increases its LDL production.
ā¢ High levels of LDL cholesterol are associated with elevated
risk of heart disease.
ā¢ LDL cholesterol is the ābad cholesterolā of the popular
literature.
28. ā¢ The intestine and the liver release HDL. HDL particles contain
Apo-C and Apo-E,which can be transferred to VLDL and
chylomicrons to allow the metabolism of those particles.
HDL also contains Apo-A-I, which functions as an activator of
Lethicin:cholesterol acyltransferase (LCAT)
ā¢ LCAT transfers acyl chains from phospholipids to cholesterol.
ā¢ Apo-A is the ligand for the HDL receptor. HDL binds its
receptor in liver and transfers accumulated cholesterol and
cholesteryl esters to the liver for processing.
ā¢ The HDL is then either released or degraded.
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29. ā¢ High levels of HDL are associated with reduced risk of
heart disease, possibly due to increased cholesterol
scavenging by HDL, and therefore lower LDL and total
plasma cholesterol levels. (HDL cholesterol is the āgood
cholesterolā of the popular literature.)
ā¢ Exercise is associated with an increase in HDL levels.
ā¢ Females have higher HDL until menopause; this is
strongly correlated with lower risk of heart disease, and
an increase in risk as HDL levels fall after menopause
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30. Transport of Dietary Fat to the Liver
Intestinal cells package
dietary fat (mostly TG)
into chylomicrons
Chylomicrons pick up
proteins from HDL
Lipoprotein lipase (LPL)
removes TG for use in
tissues (Apo-C-II
activatesLPL)
Chylomicron remnant
are taken up by the
liver
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31. Export of Fat from the Liver
TG and cholesterol is
exported from the liver
as nascent VLDL
VLDL picks up proteins
from HDL
Lipoprotein lipase (LPL)
removes TG for use in
tissues (Apo-C-II
activates LPL)
VLDL is transformed to
LDL during circulation
LDL delivers cholesterol
to tissues by receptor
mediated uptake
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32. Role of HDL in Lipid Metabolism
Nascent HDL is exported
from liver and intestinal
cells
Free cholesterol is picked
up from cells and other
lipoproteins, along with
other components
LCAT converts cholesterol
to cholesterol esters (CE)
CE is transferred to other
lipoproteins
HDL returns cholesterol
to the liver
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34. The fatty
acid
breakdown
pathway
ā¢ The reactions involved in the
actual breakdown of free fatty
acids occur in the
mitochondria. While short
chain fatty acids (about 10
carbons or shorter) enter the
mitochondria by diffusion, long
chain fatty acids require
activation and translocation.
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35. Activation
of fatty
acids
The enzyme acyl-CoA
synthetase catalyzes the
formation of a thioester bond
between a fatty acid and
coenzyme A. Thioester links are
high-energy bonds; acyl-CoA
synthetase uses the energy
from ATP to drive the formation
of the thioester.
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36. Translocation
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Once activated by conjugation to coenzyme A,
the acyl-CoA must be transported into the
mitochondria. Entry of the activated fatty acid
into the mitochondria is a multistep process. In
order to maintain separate cytoplasmic and
mitochondria pools of coenzyme A, the
transport process uses a separate small
molecule,carnitine.
The cytosolic enzyme carnitine acyltransferase I
reversibly exchanges the thioester bond to
coenzyme A in the acyl-CoA for an ester bond
to carnitine. Carnitine acyltransferase I is
inhibited by malonyl-CoA, the substrate for
fatty acid biosynthesis. Because entry into the
mitochondria is required for breakdown of fatty
acids, and because only the acyl-carnitine can
enter the mitochondria, carnitine
acyltransferase I acts as a major control point
for fatty acid breakdown
37. Long-chain fatty acids
ā¢ Fatty acids above a certain size (greater than 22 carbons)
cannot enter the mitochondria.
ā¢ Instead, these compounds are metabolized in another type
of subcellular organelle, the peroxisome.
ā¢ The peroxisomal b-oxidation pathways are basically similar
to those of the mitochondria, except that the peroxisomal
acyl-CoA dehydrogenase releases its electrons by forming
hydrogen peroxide rather than by donation to the electron
transport chain, because the electron transport pathway
does not exist in the peroxisomes.
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38. Contā¦.
Peroxisomal b-oxidation stops with short acyl chains (4 to 8-
carbons) because the peroxisomal thiolase will not cleave
shorter acyl chains. The short chain acyl-CoA isconverted to
acyl-carnitine, which then goes to mitochondria to be
metabolized to acetyl-CoA.
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39. Contā¦.
ā¢ Long chain fatty acids diffuse into peroxisomes unassisted
(neither carnitine nor activation of the fatty acid is
necessary). Once in the peroxisome, a peroxisomal acyl CoA
synthetase activates the long chain fatty acids. Acetyl-CoA
produced in the peroxisomes is released to the cytoplasm
ā¢ Fatty acids containing double bonds, odd-numbers of
carbons, or branched b carbons require somewhat modified
pathways for metabolism.
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40. Summary
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Definition of Lipids
Classification of
Lipids
Digestion of lipids Lipoproteins
Apoproteins
Lipoprotein
pathways
Transport and
export of lipids
Role of HDL
Fatty acid
breakdown
pathway
Short chain and
long chain
breakdown
pathway
Summary References
41. References
12/30/2023 LIPID METABOLISM (Dr Akshay Shetty) 41
Guyton s Physiology
www.lipidmetabolism.org
www.lipoprotien.edu.in
www.youtube.com
Boron s Book of physiology