BIOSYNTHESIS OF

MEMBRANE LIPIDS
DEFINITION OF TERMS
BIOSYNTHESIS

• It is a multi-step, enzyme-catalyzed process where substrates are

converted into more complex products in living organisms.

• In biosynthesis, simple compounds are modified, converted into other

compounds, or joined together to form macromolecules.
• This process often consists of metabolic pathways. Some of these
biosynthetic pathways are located within a single cellular organelle,
while others involve enzymes that are located within multiple cellular
organelles.

• Examples of these biosynthetic pathways include the production of

lipid membrane components and nucleotides. Biosynthesis is usually
synonymous with anabolism.
ANABOLISM

• Anabolism or biosynthesis is the set of biochemical reactions that

construct molecules from smaller components.

• Anabolism and catabolism are the two broad classes of biochemical

reactions that make up metabolism.

• Anabolism is the synthesis of complex molecules from simpler ones.

These chemical reactions require energy.
 MEMBRANE LIPIDS
• A group of compounds (structurally
similar to fats and oils) which form
the double-layered surface of all
cells (lipid bilayer).

• Membrane lipids are classified

based on the properties of ‘head’
group.
Illustration of
Membrane Lipids
• Membrane lipids have hydrophilic (polar) and hydrophobic ( non-
polar) parts

• One end is hydrophilic and the other end is hydrophobic (amphipathic)

• Their hydrophobic interactions with each other and their hydrophilic

interaction with water direct the packing of lipids in the membrane .

• We commonly represent the polar part of membrane lipid as ‘Head’

and the non-polar part as ‘tail’.
• In the glycerophospholipids and the sphingolipids the fatty acid
hydrocarbon chains are hydrophobic whereas the polar headgroups
are hydrophilic.

• In cholesterol the entire molecule except for the hydroxyl group on

carbon-3 is hydrophobic
MEMBRANE LIPIDS

• Bio-membranes are asymmetric.

• Components of two faces always differ from each other.

• Long Hydrocarbon chains of fatty acid forms the hydrophobic part.

• Hydrophilic moieties of the membrane lipids may be as simple as

single –OH at one end of the sterol ring system or they may be much
complex.
 • Membranes are two layer thick sheath like
Biological Membrane
structure.
System:
• Formed by non-covalent assemblage of lipids and
proteins.

• Mainly consists of Lipids, Proteins and

Carbohydrates.

• Membrane forms closed boundaries between

different compartments.

• Acts as barriers to the passage of polar molecules

and ions.
• Membrane lipids of Prokaryotes, Eukaryotes and Archaebacteria are
grouped into FOUR major categories:

- Phospholipids
- Glycolipids

- Sterols

- Archaebacterial Ether Lipids

Biosynthesis of Membrane Lipids and Steroids
Membrane Lipids and Steroids

Phospholipids

1. Phosphatidate is a common intermediate in

synthesis of phospholipids and
triacylglycerols
2. Cholesterol is synthesized from acetyl-CoA
3. Regulation of cholesterol synthesis at
several levels
4. Derivates of cholesterols -> bile salts,
steroid hormones,…
Synthesis of Phospholipids and Triacylglycerols
 Phosphatidate is a Common
Intermediate in Synthesis of
Phospholipids and Triacylglycerols

Phosphatidic acid (mammalians) is

synthesized in the endoplasmic reticulum and
outer mitochondrial membran

Phosphatidic acid mainly synthesized from

dihydroxyacetone phosphate (glycolysis)

R1 is usually saturated
R2 is usually unsaturated
Synthesis of Triacylglycerols

Synthesized in Endoplasmic
reticulum of the liver
Transport of TAG from liver
to muscles (for energy
conversion) or adipocytes
(storage)
Phospholipids
Phospholipids
Activation of Intermediate for Synthesis of Phospholipids

(Cytidine diphosphate)
Synthesis of Phospholipids
Synthesis of Phospholipids
 Sphingolipids

X=H -> Ceramide

Sphingolipids are found in plasma membrane of Eukaryotes

-> Produced from Ceramides
Highest concentration in central nervous system
Possible role of lipids: second messangers -> i.e. initiate cell death
Synthesis of Sphingolipids

Gangliosides

Cholera doxin -> binds to gangliosides ->

Development of cholera (severe diarrhea)

Gangliosides are crucial for binding of immune

Sphingolipids System cells to sites of injury (inflammation)
 Steroids

Cholesterol
Synthesis of Cholesterol
 Regulation of Cholesterol Biosynthesis

Cholesterol obtained from:

1. Diet
2. Synthesized de novo

Synthesis in mammals: Liver and Intestine

Regulation of synthesis mainly by feedback regulation of 3-

hydroxy-3-methylglutary CoA reductase (HMG CoA
reductase)

1. Rate of synthesis of mRNA of reductase

2. Rate of translation of reductase
3. Degradation of reductase
4. Phosphorylation decreases activity

Regulatory mechanism are modulated by receptors that sense

cholesterol on blood

31
Core of hydrophobic lipids surrounded by a shell of more hydrophilic lipids
 Diet

Triacylglycerols +

Cholesterol

High in Cholesterol of diet

Triacylglycerol
content (99%)
-> low density

LDL is major carrier of cholesterol in blood and regulates de novo synthesis

-> High LDL -> “Bad Cholesterol” -> Atherosclerosis
HDL (“Good cholesterol”) is a shuttle that moves cholesterol throughout the
body -> to use it or to produce hormones
Regulation of Cholesterol Biosynthesis

Diet
 LDL Regulates Cholesterol Metabolism
Cholesterol synthesis
Liver cell engaged in
synthesis and secretion of
VLDL
Endocytosis of LDL bound to its receptor
1. Apoprotein B-100 (on surface of LDL) binds to specific
receptor
2. Receptor-LDL complex initiates endocytosis
3. Vesicles fuse with Lysosomes -> Break down of Protein and
Lipids (Lipase)
4. Cholesterol can be used for membrane biosynthesis or
reesterfied for storage
Receptor-Mediated Endocytosis
 Cholesterol Biosynthesis Blocker

Potent blocker of HMG CoA reductase -> reduce level of synthesized cholesterol
 Cholesterol Derivates – Bile Salts

The only way we can get

rid of excess of
cholesterol ->
cholesterol derivates
-> mainly produced bile
salts !!!

cysteine

Major bile salt

Bile salts are cholesterol derivates.

-> highly efficient detergents, help to solubilize dietary lipids
-> synthesized in liver, stored in gall bladder, released into small intestine
Cholesterol Derivates – Steroid Hormones

(Androgens)
 Nomenclature of Steroid Hormones

Steroid hormones are

hydroxylated by Cyt P450

3α or 3β hydroxy
5α or 5β hydrogen

Below plane Above plane

Trans fusion Cis fusion
Steroid hormones Bile salts
Synthesis of Precursor for Steroid Hormones
Synthesis of Progesterone and Corticosteroids
Synthesis of Androgens and Estrogens
 Synthesis of Vitamin D

In the liver + kidney

Plays an important role in Calcium and Phosphorus metabolism

Isoprenoids
β-Carotinoids