Lipids and Membranes
Presented by
Dr. Mohammad Saadeh
The requirements for the Pharmaceutical Biochemistry I
Philadelphia University
Faculty of pharmacy
Lipids and Membranes
I. overview
Lipids are related fatty acids (esters of fatty acids with
alcohol).
1. They are essential components of all living organisms with
widely varied structures.
2. They are insoluble in water and soluble in organic solvents.
3. They are either hydrophobic (nonpolar) or amphipathic
(containing both nonpolar and polar).
Lipids and Membranes
II. Structural and functional diversity of lipids
** Simplest lipids, fatty acids (esters of fatty acids with alcohol),
have general formula R-COOH (R represent hydrocarbon chain)
these can be divided into two groups.
a. Fats (saturated or unsaturated), are the ester of fatty acids with
glycerol (oil)
b. Waxes, are the ester with higher alcohols (cetyl alcohol).
** Complex type of lipids, including triacylglycerols,
glycerophospholipids, and sphingolipids.
* Phospholipid, lipids containing phosphate groups.
* glycosphingolipids, lipids containing sphingosine and
carbohydrate
* isoprenoids, stroid, lipid vitamins, and terpenes are related to the
five- carbon molecule isoprene.
Lipids and Membranes
II. Structural and functional diversity of lipids
Some function of lipids,
1. Biological membranes contain amphipathic lipids (sphingolpid).
2. Intracellular storage molecules for metabolic energy.
(triacylglycerols).
3. A dipos tissue occurs under the skin and in the abdominal cavity,
so they serve as thermal insulation and padding.
4. Steroid hormones regulate metabolic activities.
5. eicosanoids, regulation of blood pressure.
6. Glycosphingolipid, located in the cell surface and participate in
cellular recognition.
7. They carry fat-soluble vitamins A, D, E and K.
Lipids and Membranes
III. Fatty acids
1. Fatty acids differ from one
another in 1. the length of their
hydrocarbon tails, 2. the number of
C-C double bonds, 3. the positions
of the double bonds in the chains,
and 4. the number of branches.
2. pKa of fatty acid about 4.5-5
therefore the fatty acids ionized at
physiological pH.
3. Fatty acids are form detergent
because they have a long
hydrophobic tail and a polar head.
4. Fatty acids are joined to other
molecules by an ester linkage at
terminal carboxyl group.
Lipids and Membranes
III. Fatty acids
5. saturated fatty acid don't
contain C-C double bond.
6. unsaturated fatty acid,
contain two or more C-C
double bond.
7. Saturated fatty acids are
waxy solids at RT (22˚c).
8.Unsaturated fatty acids are
liquids at RT (22˚c).
9. The lengths of hydrocarbon
tails increase, the melting
points of fatty acids increase.
III. Fatty acids
10. The configuration of the double bonds in unsaturated fatty acids is
generally cis.
11. In IUPAC, ∆n, n indicates the lower-numbered carbon atom of each
double-bonded pair.
Lipids and Membranes
III. Fatty acids
12. Fatty acids occur in trace amount in living cells. Most fatty acids are
esterified to glycerol or other backbone compounds to form more
complex molecules, example: fatty acids laurate and linoleoly called
lauroyl and linoleoyl ester respectively.
13. The most abundant fatty acids in animals are usually oleate (18:1),
palmitate (16:0) and stearate (18:0).
12. Mammals require certain dietary polyusaturated fatty acids that they
no synthesized, such as linoleate (18:2) (plant oil), and linolenate (18:3)
(fish oil). Such fatty acids called essential fatty acids.
Lipids and Membranes
III. Fatty acids
Saturated fatty acids
Unsaturated fatty acids
Lipids and Membranes
IV. Triacylglycerols
*Fatty acids are important metabolic fuels.
*The oxidation of fatty acids yield more
energy (≈37kJ/g) than oxidation of proteins
or carbohydrates (≈16kJ/g).
*Fatty acids are generally stored as neutral
lipids called triacylglycerols.
*Triacylglycerols (triglycerides) are
composed of three fatty acyl residues
esterified glycerol, a three-carbon alcohol
(see figure).
Triacylglycerols are very hydrophobic (*can not form bilayers), so they can
be stored in cells in an anhydrous form (not solvated by water).
Glycerophospholipids (phosphoglyceride)
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•
•
•
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two types: 1. Glycerophospholipid 2. Plasmalogens
The most abundant in membranes are glycerphospholipids SUCH AS
Have a glycerol backbone.
The simplest Glycerophospholipids (phosphatidates), consist of two fatty
acyl groups esterified to C-1 and C-2 of glycerol 3-phosphate (Table 9.2). (In
general, saturated fatty acids esterified to C-1and unsaturated fatty acids
esterified to C-2, (note: triglyceride, three fatty acyl groups esterified to
glycerol)
The phosphate group is esterified to both glycerol and another compound
bearing an –OH group (Table 9.2).
Glycerophospholipids are amphipathic molecules, with a polar head and
long nonpolar tails (Figur 9.7).
Glycerophospholipids (phosphoglycerides)
Glycerophospholipids are amphipathic molecules, with a polar head and long
nonpolar tails (Figur 9.7).
Glycerophospholipids (phosphoglycerides): The specific positions of fatty acids
in glycerophospholipids can be determined by using
1. phosphlipase A1 catalyze the hydrolysis of the ester bonds at C-1 and produce
fatty acids
2. phosphlipase A2 (present in snake, bee, and wasp venom) catalyze the
hydrolysis of the ester bonds at C-2 and produce fatty acids resulting
hydrolysis RBCs (figure 9.8).
3. phosphlipase C catalzes hydrolysis of the P-O bond between glycerol and
phosphate to liberate diacylglycerol (DAG)
4. phosphlipase D converts glycerophospholipids to phosphatidates (figure 9.8).
Glycerophospholipids (phosphoglycerides):
Glycerophospholipids
(phosphoglycerides):
 Plasmalogens is one of the
major type of
glycerophospholipids, differ
from phophatidates in having
the hydrocarbon substituent on
the C-1 hydroxyl group of
glycerol attached by a vinyl
ether linkage rather than
ester linkage (figure 9.9).
 Plasmalogens abundant in the
human central nervous system.
Sphingolipids:
Sphingolipids are abundant in tissues of the central nervous system.
• Sphinglipids is sphingosine (trans-4-sphingenine), an unbrached C18
alcohol with a trans double bond between C-4 and C-5, an amino
groups at C-2 and hydroxyl groups at C1 and C-3 (figure 9.10a).
Types of sphingolipids: 1. Ceramide; 2. Sphingomyelins; 3. Cerebrosides; 4.
Gangliosides
1. Ceramide consists of a fatty acyl group linked to the C-2 amino group of
sphingosine by an amide bond (figure 9.10b). Ceramide are the metabolic
precursors of all sphingolipids.
2. Sphingomyelins, contain phosphate (phospholipid), phosphocholine is
attached to the C-1 hydroxyl group of ceramide (zwitterions) (figure 910c). Sphingomyelins are present in plasma membranes of the most
mammalian cells and a major component of myelin sheaths that surround
certain nerve cells.
Sphingolipids:
Sphingolipids:
3. Cerebrosides
are glycosphingolipids that contain
one monosaccharide residue attached
by a β-glycosidic linkage to C-1 of a
ceramide. Example,
galactocerebrosides known as
galactosylceramides, are abundant in
nerve tissue and account for about
15% of the lipids of myelin sheaths
(β-D-galactosyl, β-D-glucosyl residue
as a head polar and non polar tail)
(figure9.11).
Sphingolipids:
4. Gangliosides are more complex glycosphingolipid in which
oligosaccharide chains containing N-acetyleneuramimic acid (NeuNAc) are
attached to a ceramide. An acetylated derivative make the head group of
gangliosides anionic. The structure of ganglioside, GM2 (Figure 9.12).
Sphingolipids:
In all gangliosides, the ceramide is linked through its C-1 to a β-glucosyl
residue, which in turn is bound to a β-galactosyl residue.
• Gangliosides are present on cell surfaces, with two hydrocarbon
chains of the ceramide moiety embedded in the plasma membrane and
the oligosaccharides on extracellular surface that are divers with
glycoprotein.
• These markers provide cells with distinguishing surface markers that
can serve in cellular recognition and cell-cell communication.
Structures similar to the ABO blood group antigens on the surface of
human cells.
• The composition of membrane glycosphingolipids can change during
the development of malignant tumors.
Steroids
Steroid cholesterol (non polar) is synthesized by mammalian cells.
It is an important component of animal plasma membranes,
essential precursor of steroid hormones and bile salts.
Other biologically important lipids
Many kinds of lipids not found in membranes such as 1. waxes, 2.
eicosanoids, and 3. some isoprenoids.
1. Waxes are very water insoluble, high melting point, non polar ester of
long-chain monohydroxylic alcohols.
For example, myricyl palmitate, a major of beeswax, is the ester of palmitate
(16:0) and the 30-carbon myricyl alcohol (figure 9.17) and ear wax.
Waxes are widely distributed in nature provide protective waterproof coating
on leaves and fruits and on animal skin, fur, feathers, and exoskeletons.
Other biologically important lipids
1. Eicosanoids are oxygenated derivatives of C20 polyusaturated fatty acids
such asarachidionic acid.
2. Prostaglandins are ecosanoids that have cyclopentane ring (b,c,d in the
figure 9.18).
Pathological response
Cause contraction of blood vessels
Formation of blood clot
Mediator of smooth-muscle contraction
3. Some isoprenoids such as the lipid vitamin A,D, E, and K.