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Lipid BSc Semester-II-Unit-II
1. Lectured by :
Dr. Wazid Hassan, PhD
KIMSICON Hospital , Vizag, AP, INDIA
Biochemistry class
Lipid (Unit-II) BSc Nursing
2. LIPID
Lipids differ from the other classes of naturally occurring biomolecules
(carbohydrates, proteins, and nucleic acids). Lipids are more soluble in
non-to-weakly polar solvents (diethyl ether, hexane, dichloromethane) than
they are in water. In spite of the number of different structural types,
Lipids share a common biosynthetic origin in that they are ultimately
derived from glucose.
Fats and oils are naturally occurring mixtures of triacylglycerols, also
called triglycerides. They differ in that fats are solids at room temperature
and oils are liquids. We generally ignore this distinction and refer to both
groups as fats.
Fats are composed of fatty
acids and glycerol. A fatty
acid is made up of a chain
of carbon atoms, with a
methyl group at one end
and an acid group at the
other. Each carbon atom in
between has either one or
two hydrogen atoms
bonded to it.
3. Triacylglycerols are built on a glycerol framework:
All three acyl groups in a triacylglycerol may be the same, all three
may be different, or one may be different from the other two.
The structures of two typical triacylglycerols, 2-oleyl-1,3-
distearylglycerol and tristearin. Both occur naturally—in cocoa butter,
for example.
All three acyl groups in tristearin are stearyl (octadecanoyl) groups. In 2-
oleyl-1,3-distearylglycerol, two of the acyl groups are stearyl, but the
one in the middle is oleyl (cis-9-octadecenoyl).
Fats have at one end of the
carbon chain is the acid
group which is able to bond
with the glycerol molecule.
Three fatty acids combine
with one molecule of glycerol
to form a triglyceride. The fat
found in food is made up of
triglycerides.
4. Classification of fatty acid
1. Length of fatty acids
I. Short-chain fatty acids (SCFAs) are fatty acids with aliphatic tails of five or
fewer carbons (e.g. butyric acid).
II. Medium-chain fatty acids (MCFAs) are fatty acids with aliphatic tails of 6 to
12 carbons, which can form medium-chain triglycerides.
III. Long-chain fatty acids (LCFAs) are fatty acids with aliphatic tails of 13 to
21 carbons.
IV. Very long chain fatty acids (VLCFAs) are fatty acids with aliphatic tails of
22 or more carbons.
2. Even and odd-chained fatty acids
I. Most fatty acids are even-chained, e.g. stearic (C18) and oleic (C18),
meaning they are composed of an even number of carbon atoms.
II. Some fatty acids have odd numbers of carbon atoms; they are referred to
as odd-chained fatty acids (OCFA). The most common OCFA are the
saturated C15 and C17 derivatives, pentadecanoic acid and
heptadecanoic acid respectively, which are found in dairy products.
III. On a molecular level, OCFAs are biosynthesized and metabolized
slightly differently from the even-chained relatives.
5. If the fatty acid has all
the hydrogen atoms it
can hold, it is said to be
saturated.
If some of the hydrogen
atoms are missing and
have been replaced by
one or more double
bonds between the
carbon atoms, then the
fatty acid is said to be
unsaturated.
Saturated or unsaturated fatty acids
6. Mono and polyunsaturated fatty acids
If there is one double
bond the fatty acid is
known as a
monounsaturated fatty
acid.
If there is more than one
double bond then the fatty
acid is known as a
polyunsaturated fatty acid.
7. Clinical significance of MUFA & PUFA
Foods containing monounsaturated fats may affect low-density
lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL)
cholesterol.
In children, consumption of monounsaturated oils is associated with
healthier serum lipid profiles.
Because of their effects in the diet, unsaturated fats
(monounsaturated and polyunsaturated) are often referred to as
good fats; while saturated fats are sometimes referred to as bad fats.
Some fat is needed in the diet, but it is usually considered that fats
should not be consumed excessively, unsaturated fats should be
preferred, and saturated fats in particular should be limited.
9. Trans Fatty acid
A trans configuration, by contrast, means that the adjacent two hydrogen
atoms lie on opposite sides of the chain. As a result, they do not cause the
chain to bend much, and their shape is similar to straight saturated fatty
acids. Most fatty acids in the trans configuration (trans fats) are not found in
nature an are the result of human processing (e.g., hydrogenation).
Example :-Elaidic acid
Cis Fatty acid
A cis configuration means that the two hydrogen atoms adjacent to the
double bond stick out on the same side of the chain. The rigidity of the
double bond freezes its conformation and, in the case of the cis isomer,
causes the chain to bend and restricts the conformational freedom of the
fatty acid. For example, Oleic acid
10. The word ―essential‖ as applied to naturally occurring organic substances
can have two different meanings. For example, as used in the previous
section with respect to fatty acids, essential means ―necessary.‖ Linoleic acid
is an ―essential‖ fatty acid; it must be included in the diet in order for
animals to grow properly because they lack the ability to biosynthesize it
directly.
Essential fatty acids, or EFAs, are fatty acids that humans and other animals
must ingest because the body requires them for good health,but cannot
synthesize them.
Only two fatty acids are known to be essential for humans: alpha-linolenic
acid (an omega-3 fatty acid) and linoleic acid (an omega-6 fatty acid). These
are supplied to the body either as the free fatty acid, or more commonly as
some glyceride derivative. Deficiency in these fatty acids is rare. These fatty
acids are essential because they are precursors to vitamins, cofactors, and
derivatives, including prostaglandins, leukotrienes, thromboxanes, lipoxins,
and others.
When the two EFAs were discovered in 1923, they were designated "vitamin
F", but in 1929, research on rats showed that the two EFAs are better
classified as fats rather than vitamins.
Essential fatty acids
11. Dietary fat composition
More than 95% are triglycerides, the other are
Cholesterol,
Cholesteryl esters,
Phospholipids, and
Unesterified fatty acids.
Digestion of Lipid
1. Pancreatic lipase with co-lipase.
2. Cholesterol esterase.
3. Phospholipase A2.
4. The bile (pH 7.7)
– Neutralise the acid of the stomach
– Provides favourable pH.
– Action of pancreatic enzymes occur.
Lipolytic enzymes in intestine
12. Triglycerides are degraded by lipases to form free fatty
acids and glycerol
Gastric Lipase
Secreted in small quantities. More effective at alkaline pH (average pH 7.8).
Requires the presence of Ca++. Less effective in stomach due to acidic pH
except when intestinal contents are regurgitated in to the gastric lumen .
Not effective for long chain fatty acids, most effective for short and medium
chain fatty acid. Milk, egg yolk, and fats containing short chain fatty acids
are suitable substrates for its action.
Lipid Digestion
13. Emulsification and digestion
Lipids are hydrophobic, and thus are poorly soluble in the aqueous
environment of the digestive tract. The digestive enzyme, lipase, is water
soluble and can only work at the surface of fat globules. Digestion is greatly
aided by emulsification, the breaking up of fat globules into much smaller
emulsion droplets Triacylglycerol digestion occurs at lipid-water interfaces
rate of TAG digestion depends on surface area of this interface which is
increased by churning peristaltic movements of the intestine , combined
with the emulsifying action of bile salts. The critical process of
emulsification takes place in the duodenum.
Digestion in small intestine: Major site of fat digestion Effective digestion
due to the presence of Pancreatic lipase and bile salts. Bile salts act as
effective emulsifying agents for fats Secretion of pancreatic juice is
stimulated by Passage of acid gastric contents in to the duodenum by
secretion of Secretin, Cholecystokinin and Pancreozymin, the gastro
intestinal hormones.
Lipid Digestion cont..
14. Emulsification and Digestion of Triglycerides
STEPS:
1. Emulsification of fat droplets by bile salts
2. Hydrolysis of triglycerides in emulsified fat droplets
into fatty acid and monoglycerides
3. Dissolving of fatty acids and monoglycerides into
micelles to produce "mixed miscelles"
17. Absorption of lipid by intestinal mucosal cells
TAGs are combined with membrane
& water soluble proteins to form a
chylomicron, a lipoprotein.
Chylomicrons carry TAGs from
intestinal cells into bloodstream via
the lymph system.
19. Overview of events that must occur before triacyglycerols
(TAGs) can reach the bloodstream through the digestive
and absorption process
20. Lipid Metabolism
Lipid Catabolism
Fat catabolism (lipolysis)
Β-Oxidation of Fatty Acids
Other Oxidations of Fatty Acids
Ketone Bodies Formation and Utilization
Lipid Anabolism
Synthesis of glycerol
Synthesis of fatty acid
Synthesis of cholesterol
21. Fat catabolism (lipolysis)
TAGs hydrolyzed
a 3rd time
to form fatty acids.
Triacylglycerol lipase
Diacyclglycerol lipase
Monoacylglycerol
lipase
Only triacylglycerol
lipase is activated by
epinephrine.
22. Glycerol Catabolism
One glycerol formed for each TAG hydrolyzed.
Enter bloodstream & go to liver or kidneys for
processing.
Converted in 2 steps to Dihydroxyacetone
phosphate
Dihydroxyacetone phosphate is an intermediate for Glycolysis: converted to
Pyruvate, then to Acetyl CoA, & eventually to CO2, releasing its energy.
Gluconeogenesis: creates Glucose from non-carbohydrate source Lipid metabolism &
carbohydrate metabolism are connected.
Uses up one ATP
Reduces one NAD+ to NADH
Primary hydroxyl group
is phosphorylated
Oxidized to form a
Ketone
23. Fatty acid catabolism
Fatty acids can also be broken down for energy.
Fatty acid catabolism can be subdivided into 3 stages
Stage 1. Activation of Fas: Acyl-CoA Synthetase (Thiokinase) which locates on the
cytoplasm, catalyzes the activation of long chain fatty acids. Key points of FA
activation : irreversible, consume 2~P, site:cytosol
Stage 2. Transport of acyl CoA into the mitochondria (rate-limiting step):
Carrier : carnitine, Rate-limiting enzyme Carnitine acyltransferase I
24. Stage 3. β-oxidation of FAs : Β-oxidation means β-C reaction. It is 4
steps in one round :
Step 1: Dehydrogenate
Step 2: Hydration
Step 3: Dehydrogenate
Step 4: Thiolytic cleavage
The important of fatty acid carbon numbers for oxidation process
Fatty acid catabolism cont..
28. Lipid metabolism disorders
Gaucher Disease:
Type 1- It is most common form, causes liver and spleen enlargement, bone pain and
broken bones, and, sometimes, lung and kidney problems. It does not affect the
brain. It can occur at any age.
Type 2- which causes severe brain damage, appears in infants. Most children who
have it die by age 2.
Type 3- In this may be liver and spleen enlargement. The brain is gradually affected.
It usually starts in childhood or adolescence.
Tay-Sachs Disease
Tay-Sachs disease is a rare, inherited disease. It causes too much of a fatty
substance to build up in the brain. This causing mental and physical problems.
Hypercholesterolemia ƒ
↑ total CH, LDL (and all apoB particles) ƒ
,↓HDL (apoA particles)
– risk factor of atherosclerosis
Hypertriglyceridemia ƒ
↑ TAG ,↓ HDL ,– risk factor of atherosclerosis
Familiar hypercholesterolemia (FH) ƒ
the most common primary HLP ,ƒ
FH
is caused by mutations in the LDLR gene (chromosome 19)
29. Cholesterol Structure
• Cholesterol (C27H46O) is most important
animal steroid, maintains membrane
fluidity, insulating effect on nerve fibres
• Cholesterol is the parent molecule for
1. Bile acids
2. Vitamin D3 (Cholecalciferol)
3. Steroid hormones
I. Progestogens
II. Glucocorticoids
III. Mineralocorticoids
IV. Androgens
V. Estrogens
Cholesterol derived compound
31. Acetone
Acetoacetic acid
(R)-beta-Hydroxybutyric acid
Ketone bodies are water-soluble molecules or
compounds that contain the ketone groups
produced from fatty acids by the liver
(ketogenesis).
Ketone bodies are readily transported into
tissues outside the liver, where they are
converted into acetyl-CoA (acetyl-Coenzyme
A)which then enters the citric acid cycle
(Krebs cycle) and is oxidized for energy.
These liver-derived ketone groups include
acetoacetic acid (acetoacetate), beta-
hydroxybutyrate, and acetone, a spontaneous
breakdown product of acetoacetate.
KETONE BODIES
32. Significance:
Normal Insulin activity do not promote Ketogenesis.
Low Insulin activity promotes Ketogenesis.
High Glucagon Promotes Ketogenesis.
KETONE BODIES cont..
33. Lipoproteins
Lipoproteins are biochemical assemblies with the primary function
of transporting and delivering triglycerides and cholesterol to and
from target cells in a variety of organs. These lipids must be
transported in association with proteins due to the insoluble nature
of triglycerides, and cholesterol in water. Lipoproteins transport
these hydrophobic lipid molecules through water, such as blood
plasma or other extracellular fluids.
Lipoproteins are five types are
1. Chylomicrons,
2. Very-low-density lipoproteins (VLDL)
3. Intermediate density lipoproteins (IDL)
4. Low-density lipoproteins (LDL)
5. High-density lipoproteins (HDL)
35. Class
Diameter
(nm) Source and Function
Major
Apoliproteins
Chylomicrons
(CM)
500
Largest
Intestine. Transport of
dietary TAG
A, B48, C(I,II,III)
E
Very low density
lipoproteins
(VLDL)
43 Liver. Transport of
endogenously synthesised
TAG
B100, C(I,II,III) ,
E
Low density
lipoproteins
(LDL)
22 Formed in circulation by
partial breakdown of IDL.
Delivers cholesterol to
peripheral tissues
B100
High density
lipoproteins
(HDL)
8
Smallest
Liver. Removes ―used‖
cholesterol from tissues
and takes it to liver.
Donates apolipoproteins
to CM and VLDL
A, C(I,II,III), D, E
Types of Lipoprotein
(all contain characteristic amounts TAG, cholesterol, cholesterol esters,
phospholipids and Apoproteins – NMR Spectroscopy)
Increasing
density
37. Lipid Profile
A lipid panel or lipid profile test assesses to identify dyslipidemia and to
screen the risk for cardiovascular disease in a person. It is a combination
of various blood tests, which is performed to measure the levels of 4 types
of lipids in our blood such as
• Total cholesterol (TC)
• Low-density lipoprotein cholesterol (LDL cholesterol)
• High-density lipoprotein cholesterol (HDL cholesterol)
• Triglycerides (TAG)
Lipid Profile Test Procedure
The doctor may ask patient to fast before undergoing a lipid profile test. The
samples are taken after 12-14 hours of overnight fasting so that the results
will be more accurate. The patient can drink clear fluids such as water, they
should avoid drinking beverages such as coffee and tea. Before the lipid profile
test, they have to take certain precautions. They need to-Avoid drinking
alcohol, high-fat food, and strenuous exercise. Most probably, their blood will
be drawn in the morning. Sometimes, test can undergo without fasting.
Fasting isn’t required, for children, teenagers and adults up to age 24.
38. Normal Cholesterol Level
The level of cholesterol in our blood is normally
measured in milligrams per deciliter (mg/dL). Lipid
profile normal range is-
Total cholesterol normal range- lower than 200mg/dL
LDL cholesterol range- between 70 to 130mg/dL
HDL cholesterol range- between 40 to 60mg/dL
Triglycerides- between 10 to 150 mg/dL
39.
40. Atherosclerosis????
Atherosclerosis : thickening or hardening of the arteries. It is caused by a
buildup of plaque in the inner lining of an artery. Plaque is made up of
deposits of fatty substances, cholesterol, cellular waste products, calcium,
and fibrin. As it builds up in the arteries, the artery walls become thickened
and stiff. Atherosclerosis is a slow, progressive disease that may start as early
as childhood. However, it can progress rapidly.
41. What causes????
It's not clear exactly how atherosclerosis starts or what causes it. However, a
gradual buildup of plaque or thickening due to inflammation occurs on the
inside of the walls of the artery. This reduces blood flow and oxygen supply
to the vital body organs and extremities.
Risk factors for atherosclerosis?
• High cholesterol and triglyceride levels
• High blood pressure
• Smoking
• Type 1 diabetes
• Obesity
• Physical inactivity
• High saturated fat diet
Coronary angioplasty
With this procedure, a long thin tube (catheter) is
thread through a blood vessel to the heart.
There, a balloon is inflated to create a bigger
opening in the vessel to increase blood flow.
Although angioplasty is done in other blood
vessels elsewhere in the body, percutaneous
coronary intervention (PCI) refers to angioplasty
in the coronary
arteries to permit more blood flow into the heart.
There are several types of PCI procedures,
including