Lipids

Asst.Prof.Dr. Gizem Esra Genç

University of Kyrenia, Faculty of Medicine, Department of Biochemistry
Obesity is the abnormal and excessive
accumulation of fat in the body due to
calorie intake above the daily calorie
intake.
• Cardiovascular diseases;
the most common cause of death, 17 million people die from these causes every year
• Diabetes Mellitus
• Musculoskeletal system disorders
A. Introduction
•Lipids are composed mainly of carbon and hydrogen, with small
amounts of phosphorus (P), nitrogen (N) and sulfur (S) atoms.

•They carry a significant amount of hydrocarbon chains in their

structure.
They are insoluble in water, but soluble in organic solvents such
as ether, chloroform and acetone.

Lipids exhibit hydrophobic properties (they do not like

water).
Lipids have important biological roles in the organism.
Main source of energy
Main form of energy
storage.
Lipids found around some organs and in
subcutaneous tissues have thermal
insulating functions.
 Phospholipids and sterols,
which are important structural
components of the cell
membrane, are involved in the
transmission of impulses.
Myelin sheath has a high lipid content (78-81% of its
dry weight)

Non-polar lipids function as electrical

insulators for the rapid propagation of
depolarization waves along myelin nerves.
 Involved in lipoprotein formation

• Lipoproteins are composed of lipids and proteins

• They are found in the structure of cell and mitochondrial
membranes
• They are the mode of transport of lipids in plasma
• They are found in the structure of cell and mitochondrial
membranes
• They are the mode of transport of lipids in plasma.
Fats give 9 kcal per gram, while carbohydrates give 4 kcal per gram.
- Fats give the most energy.
This is because
It contains few oxygen atoms and many C and H atoms.

Despite this, it is used in 2nd place in the body.

Because:
- Since fats contain little oxygen, they need a lot of oxygen to break down.
Difficult to break down

✓ Obese people can store 15-20 kg of triglycerides in their adipocytes, which is enough energy for months.
✓ In contrast, energy stored in the form of glycogen is sufficient for less than a day.
✓ Carbohydrates such as glucose and glycogen are fast sources of metabolic energy, with the advantage of being readily
soluble in water.
• When more carbohydrates enter the body than necessary, the excess is
immediately converted into triglycerides (fat) in the liver and stored in
adipose tissue.
• Making fat from carbohydrates is very important. This is because most
cells in the body do not have space to store excess glycogen. A person
can store 200 times more fat than he or she can store as carbohydrate.
Fat cells = adipocytes.
Adipocytes form = adipose tissue.
It is first stored in droplets and then covers the whole cell. The
cytoplasm surrounds the fat droplet in a thin line. Cell organelles are
pushed aside.
 Lipidlerin sınıflandırılması
A. Fatty acids and derivatives

B. Compound Lipids

C. Isoprene lipids
Fatty Acids

1. Sature Fatty Acids

2. Unsature Fatty Acids
3. Fatty Acids Derivatives
 Fatty Acids

1.Saturated fatty acids

• There are no double bonds in the aliphatic chains of saturated
fatty acids with the general formula CnH2n+1COOH.
• In systematic nomenclature, the suffix -anoic acid is added to the
number of carbon atoms.
• The systematic name of 18-carbon stearic acid is octadecanoic acid.
 2. Unsaturated fatty acids
• In the general formula CnH2n-aCOOH for unsaturated fatty acids
carrying one or more double bonds, “a” is replaced by the number of
double bonds.
• The carbon atoms of unsaturated fatty acids are numbered starting
from the carbon atom in the carboxyl group.
 Unsaturated fatty acids containing a double bond in the
hydrocarbon chain are monounsaturated (monoenoic) fatty acids
(MUFA)

CH3(CH2)7C=C(CH2)7COOH

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Unsaturated fatty acids containing two or more double bonds in the
hydrocarbon chain are polyunsaturated fatty acids (PUFA).
Polysaturated fatty acids are called dienoic, trienoic, tetraenoic fatty
acids according to the number of double bonds they contain.

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In unsaturated fatty acids, geometric isomers arise depending
on the placement of atomic groups on both sides of the double
bond.
If the acyl groups on both sides of the double bond are on the
same side, a cis- isomer is formed, and if they are on different
sides, a trans- isomer is formed.
 UNSATURATION IS A VERY IMPORTANT PROPERTY FOR LIPIDS IN THE
STRUCTURE OF MEMBRANES!

• Because double bonds in the cis position cause a kink in the molecule and
prevent the molecules in the membrane from being packed too close
together.
• This makes the membrane FLUID (permeable and flexible).
 Essential Fatty Acids

• Some polyunsaturated fatty acids of plant origin

cannot be made in the human body and must be
obtained from the diet.

Essential Fatty Acids

Linoleic acid
In the human body, only pairs can be added to
Linolenic acid carbons from the carboxyl carbon to the 9th carbon
of fatty acids.
Arachidonic acid
• 1928, Evans and Burr
• Rats fed a lipid-free diet
• Growth retardation and reproductive disorders, dandruff on the
skin,
• Improvement with dietary linoleic, alpha-linolenic and arachidonic
acid supplementation
 Functions of Essential Fatty Acids

• They are the building materials of eicosanoids

• They are involved in cell membrane structure and function
• They contribute to brain and nerve development
• They are involved in normal growth and vision
• They contribute to gene regulation
• Participate in the structure of the skin and play a role in preventing
water loss
• Play a role in reproduction
 Fatty acid derivatives

EICOSANOIDS
• Eicosanoids are physiologically and pharmacologically
effective compounds composed of arachidonic acid
and some 20 C polyunsaturated fatty acids.

• Prostaglandins (PG), thromboxanes (TX) and

leukotrienes (LT) belong to the eicosanoid class.

• They are also considered local hormones that

function through G protein-coupled receptors.

• Precursors Linoleic acid and Arachidonic acid

 Prostanoids

Prostanoids, containing cyclic prostanoic acid as the core structure

• prostaglandins (PG)
• prostacyclin (PGI)
• thromboxanes (TX)
PROSTAGLANDINS

• Unsaturated fatty acids with 20 C containing a

cyclopentane ring.
• Prostanoic acid is the main skeleton in prostaglandins. They
exert their hormone-like effects in all tissues except
erythrocytes.
• They are short-lived.
• They are not stored where they are synthesized.
• They lower blood pressure.
• They cause contraction of the small intestine and uterine
muscle (medical abortion)
• Some prostaglandins initiate contraction of the smooth
muscles of the uterus during menstruation and delivery.
PROSTACYCLINS

• Structurally similar to prostaglandins

• Mainly in the vascular endothelium
• Produced in small amounts in vascular smooth muscle cells
• Relaxes vascular smooth muscle
• It prevents platelet aggregation and platelet adhesion to the
endothelial surface
• Used in bypass surgeries to reduce the risk of blood clots
THROMBOXANES

• Synthesized in platelets is similar to prostaglandin.

• Their synthesis is inhibited by low-dose aspirin
• Biological effects are opposite to prostacyclin
• Increases contraction of vascular smooth muscle
• Increases the aggregation of platelets
• Thromboxanes and prostacyclins form a system
that affects platelets in opposite directions and
regulates platelet aggregation and adhesion
• Prostanoids act as “local” hormones.They affect the cells that produce them or different
types
• of neighboring cells.
• They participate in many events in the body, especially in the inflammatory response after
infection or injury.
• They produce symptoms such as pain, swelling and fever.
• They are involved in hemostasis (promoting or inhibiting aggregation).
• Regulate smooth muscle contraction (especially in the intestine and uterus).
• They increase renal excretion of water and sodium and participate in the regulation of blood
pressure.
• Prevention of gastric ulcer (reduction of HCl acid production)
LEUKOTRIENES

• They are arachidonic acid derivatives

• They are synthesized in leukocytes and degraded in a short time. They
have an unringed structure
• Contain 3 conjugated double bonds
• They cause contraction of smooth muscle and coronary vessels and
relaxation of small vessels involved in chemotaxis, inflammation and
allergic reactions
• It stimulates mucus secretion and is involved in the development of
clinical manifestations of asthma.
• Overproduction of leukotrienes leads to asthma attacks
 Lipoxins

Lipoxins are trihydroxy derivatives of arachidonic acid.

34
 Lipoxins are formed by the sequential oxidation of arachidonic acid by 15-
and 5-lipoxygenase.

Lipoxin A stimulates superoxide

anion formation in neutrophils,
causing chemotaxis.

35
 Epoxides

The main products formed from arachidonic acid in the cytochrome P450
epoxygenase pathway are epoxides (EETs).

Epoxides are vasoactive and have an effect on renal function.

36
B. Compound (Complex) Lipids
I. Neutral fats (Triacylglycerol, Triglyceride)
Triacylglycerols formed by esterification of three alcohol groups of
glycerol with fatty acids are called triglycerides, fats or neutral fats.

Hydroxyl groups of glycerol:

Monoacylglycerol (monoglyceride) if esterified with a fatty acid
Diacylglycerol (diglyceride) if esterified with two fatty acids
Triacylglycerol (triglyceride) if esterified with three fatty acids
In general, the structure of fats is in the form of triglycerides. Triglycerides are defined as simple fats if all three of the
fatty acids esterified with glycerin in triglycerides are the same, i.e. if the same type of fatty acid is present at all α, β,
α′ positions.

If the fatty acids esterified with glycerin in triglycerides are not the same, that is, if there are different types of fatty
acids at the α, β, α′ positions, triglycerides are defined as mixed fats.
Phospholipids
Phospholipids are lipids containing phosphates; they are also known as
phosphatides.

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• Phospholipids; It is the most abundant lipid type
in the cell membrane.

Phospholipids are found in high concentrations in

glands, blood plasma and egg yolk.
Phospholipids, which make up about 40% of erythrocyte
membrane lipids, constitute more than 95% of the inner
membrane of mitochondria.
2. Phospholipids
When the phosphate group in the structure of phospholipids forms the first of the two
ester bonds with glycerol, glycerophospholipids are formed, and when it forms the first
one with sphingosine, sphingophospholipids are formed.

O-X
Glycerophospholipids
Phosphatidic acid, which forms the basic structure of glycerophospholipids (phosphoglycerides), is a
phosphodiglyceride formed by esterification of two alcohol groups of glycerol with a fatty acid and
the last alcohol group with a phosphoric acid.
The phosphorus of phosphatidic acid is esterified with various alcohol groups to form different types
of glycerophospholipids.
 b. Sphingophospholipids (Sphingomyelins)
They contain 18-carbon sphingosine instead of glycerol.
Ceramide is formed when the amino group of sphingosine forms an amide bond with a fatty acid.
It is found in the plasma membranes of cell membranes, especially in brain and nervous tissue.
It provides isolation by wrapping the axons of myelinated nerve cells.
They contain 24-carbon saturated lignoceric acid and unsaturated nervonic acid as fatty acids.
Niemann-Pick disease
In Niemann-Pick disease, in which sphingomyelin degradation is impaired,
sphingomyelin accumulates in the liver, spleen and brain.
Niemann-Pick disease is caused by a rare genetic defect in sphingomyelinase,
the enzyme that hydrolytically degrades sphingomyelin, leading to mental
retardation in newborns and early death.
 Lecithin (Phosphatidylcholine)
Lecithin, formed by esterification of choline
(trimethylethanolamine) with the phosphate group of
phosphatidic acid, is the most abundant phospholipid in
the cell membrane.
• The dipalmityl lecithin form of lecithin enters the structure of
the alveolar surfactant and adjusts the surface tension
during inspiration and expiration.
• As a result, it prevents rupture and adhesion of the alveoli. It
is secreted from Type II epithelial cells of the lungs.
Approximately half of the lipid-protein mixture defined as
lung surfactant is composed of dipalmitoyl
phosphatidylcholine.
• Another important lipid component of surfactant is
phosphatidylglycerol.
Acute respiratory failure can be seen in premature infants in
whom lung surfactant cannot be produced adequately.

The lecithin/sphingomyelin (L/S) ratio in amniotic fluid is important in determining fetal lung
maturation.
L/S ratio in amniotic fluid is L/S<1 until 31 weeks,
34.week L/S  2,
36.week L/S  4,
39 weeks, L/S  8.
If the L/S ratio in amniotic fluid is below 2, there is a risk of respiratory distress syndrome (RDS),
although this is not certain.

49
3. Glycolipids (Glycosphingolipids)
• Glycolipids containing sphingosine, fatty acids, carbohydrates and carbohydrate derivatives do NOT
contain phosphorus.
• They are formed by binding one or more sugars to the primary alcohol group of sphingosine in the
ceramide structure formed by the binding of fatty acid to the amino group of sphingosine.
• Glycolipids, which are widely found in every tissue of the body, especially in the brain and nervous tissue,
are located on the outer surface of plasma membranes.

Sfingozin

Yağ asidi

Glc Gal GalNac Gal

Fuc
4. LIPOPROTEINS
The complexes formed by lipids with proteins are called LIPOPROTEINS.
They ensure the transport of lipids from the small intestine and liver into the bloodstream and from the bloodstream to
organs and tissues.
The inner core of the lipoprotein contains apolar lipids (cholesterol esters and triglycerides) and the outer shell contains
lipids with polar groups (phospholipids and free cholesterol) and proteins with important metabolic and structural
functions.
APOLIPOPROTEINS

Apolipoproteins are the protein part of lipoproteins and have 3 main functions:

1. They stabilize non-polar lipids.

2. Bind to cell surface receptors and detect the sites where lipoproteins are taken up and degraded.
3. Regulate the activity of enzymes involved in lipoprotein metabolism.
Lipoproteins are usually classified according to their physicochemical properties (especially density differences).
Thus, ultracentrifugation produces 5 classes of lipoproteins:

• Chylomicron
• VLDL (Very Low Density Lipoproteins)
• IDL (Intermediate Density Lipoproteins)
• LDL (Low-Density Lipoproteins)
• HDL (High Density Lipoproteins)
CHILOMICRONS

• They provide transport of exogenous (dietary) lipids.

• They are the largest and most triglyceride-rich lipoproteins.
• It contains the most triglycerides and the least protein in its composition.
• They are the largest of the plasma lipoproteins.
• The main apolipoproteins they carry are apolipoprotein B-48 (apoB48), apoA-I,
apoA-II and apoA-IV. ApoB48 is only found in chylomicron

Chylomicrons are not seen in electrophoresis in healthy people. Because they

disappear from the circulation within max. 1 hour after a meal.
VLDL (VERY LOW DENSITY LIPOPROTEIN)
It is rich in endogenous triglycerides. 55% triglycerides, 20% cholesterol.
Synthesized in the liver. Its function is to transport triglycerides and cholesterol synthesized in the liver to extrahepatic
tissues
When the energy load in the organism is high (overfeeding), VLDL synthesis increases
The main apolipoprotein is Apo B100.
*If lipoprotein synthesis in the liver is inhibited by various factors, endogenous triglycerides accumulate in the liver and a
condition called fatty liver disease may occur

IDL (INTERMEDIATE DENSITY LIPOPROTEINS)

50% or more of VLDL is converted to IDL.
IDL is rich in cholesterol esters.
LDL (LOW DENSITY LIPOPROTEINS)
LDL is synthesized intravascularly as a residue of VLDL.
LDL contains 70% of total cholesterol in plasma. It is the richest lipoprotein particle in cholesterol.
Its major apolipoproteins are Apo B100 and apo E.
It has receptors in extrahepatic tissues and liver. It is catabolized by binding to these receptors through Apo B 100 in its
structure. LDL is also catabolized by macrophages.
*In cases where LDL is increased in the plasma, macrophages take excessive amounts of cholesterol and “foam cells” are
formed. Increased LDL is harmful for the organism as foam cell formation causes “atherosclerosis”

HDL (HIGH DENSITY LIPOPROTEINS)

It is the smallest lipoprotein. There are at least 5 different HDL particle types.
50% of the HDL mass is protein.
Its main function is to transport cholesterol from tissues to the liver “reverse cholesterol
transport”
The function of HDL to transport cholesterol from tissues such as vascular endothelium to the
liver produces an antiatherogenic effect.
C. Isoprene lipids

Terpenes and sterol derivatives (cholesterol, bile acids, vitamin D and steroid hormones) belong to this
group.
They are formed by a series of isoprene units.
Isoprene: contains 5 C and 2 double bonds. Isoprene units are in the form of a straight chain or ringed.
Terpenes are found in the structure of biological pigments, vitamins A, D, E and K, electron carriers.

isoprene unit
1. CAROTENOIDS

Carotenes are carotenoids that do not contain oxygen atoms and carry carbon and hydrogen atoms; α-carotene, β-
carotene, lycopene, etc.

Carotene is a precursor of vitamin A. Carotenes are stored in subcutaneous adipose tissue.

Carotenoids have very important biological effects. The most prominent effects include antioxidant effect,
provitamin A effect, anticancer effect, skin protective effect, etc.
2. STEROIDS

Steroids, named after the Latin word steros, meaning solid, constitute a large subgroup of lipids.
The isoprene derivatives in their structure show a highly ringed structure.

It consists of 3 phenanthrene rings (6 C) + 1 cyclopentane rings (5C)

In the sterane system known as cyclopentanoperhydrophenanthrene ring, the rings are symbolized by the letters A,
B, C

12 18 17
16
11 13
C D
1 19 9 15
2 14
10 8
A B
3 7
5
4 6
Şekil 1 Steroid çekirdeği
Cholesterol (3-hydroxy-5,6-cholesten)
This steroid, named cholesterol because it was first obtained from gallstones in 1775, has an
eight-carbon side chain in its structure.
There is a double bond between the 5th and 6th carbons in the B ring, one of the rings in the
trans-trans-trans state. The hydroxyl group at the 3rd carbon of cholesterol is free or esterified with
fatty acids. In human plasma, about ¾ of cholesterol is ester and the rest is free.

17

3
5
HO 6

Şekil 4. Kolesterol
Cholesterol
 Cholesterol is found in all cells of the body and is especially prevalent in the brain,
nervous system and adrenal glands.
 Found in the structure of plasma membranes and plasma lipoproteins, cholesterol is
a poor electrical conductor.
 Its widespread presence in brain and nervous tissue is due to its insulator function
in these systems.
 Cholesterol, which is not found in plant organisms, is common in animal organisms.
 Steroid hormones such as bile acids, vitamin D, progesterone, cortisol, testosterones,
cortisol, testosterone, estrogens are synthesized from cholesterol, which can be taken
into the organism through diet and synthesized endogenously in the body.
Vitamin D
During the synthesis of cholesterol from lanosterol, the intermediate product 7-
dehydrocholesterol is deposited in the skin.

7-dehydrocholesterol, the precursor of vitamin D3, has 2 double bonds in the B

ring.
Bile acids
They are derived from cholesterol.
Since the ring structure of cholesterol is not
metabolized to CO2 and H2O in the human
body, cholesterol is transformed into bile
acids in the liver and given to the small
intestine.
They are called primary and secondary
according to the location of -OH groups in
their structure.
Two primary bile acids from cholesterol in the liver: cholic acid and chenodeoxycholic acid
Primary bile acids formed in the liver are converted by small intestinal bacteria into secondary bile acids, deoxycholic
and lithocholic acid

Bile acids are esterified with glycine (80%) and taurine (20%) in the
liver
 Except for lithocholic acid, the majority of bile acids are reabsorbed from
the ileum and returned to the liver

This is called enterohepatic circulation of bile acids

Bile acids, which reduce surface tension and have an emulsifying effect,
lead to emulsification of fats and oils, enabling enzymes to act more easily

Bile acids increase the activation of cholesterol esterase and lipase in the
intestine and intestinal peristalsis and play a role as a bile expectorant
Steroid hormones
They are intracellular messengers
In humans, cholesterol is the precursor compound of steroid hormones synthesized and
secreted in the adrenal cortex, testes, ovaries and placenta.
Glucocorticoids, mineralocorticoids and sex hormones are synthesized in the adrenal
cortex, testosterone in the testes, estrogens in the ovaries and progesterone in the corpus
luteum.
During pregnancy, progesterone is synthesized in the placenta
 Basic steroid hormone structures
CH3 CH3
OH OH C O C O
HO ........H

OH O O
O

17β Östradiol Testosteron Kortizol Progesteron