Phospholipids are amphipathic lipids that contain a phosphate group and two fatty acid chains. They are classified as glycerophospholipids, which contain a glycerol backbone, or sphingophospholipids, which contain sphingosine. Glycerophospholipids are synthesized from phosphatidic acid and various alcohols like choline or ethanolamine. Sphingomyelin contains sphingosine, a fatty acid, phosphate, and choline. Phospholipids form cell membranes and generate lipid signaling molecules. They also participate in fat absorption and transport.

1. BIOSYNTHESIS OF
PHOSPHOLIPIDS
A.SATHIYARAJI
BP221518
1-M.Sc APPLIED MICROBIOLOGY

2. Phospholipids
 These are compounds containing, in addition to fatty
acid and glycerol, a phosphoric acid, nitrogenous
bases and other substituent.
 Polar compounds composed of alcohol attached by
phosphodiester bridge to either diacylglycerol or
sphingosine.
 Amphipathic in nature, has a hydrophilic head
(phosphate +alcohol eg., serine, ethanolamine, and
choline) and a long, hydrophobic tail (fatty acids or
derivatives ).

3. Classification
 Phospholipids are classified according to backbone
content into: Glycerophospholipids and
Sphingophospholipids
 1. Glycerophospholipids: backbone is
glycerol,Glycerophospholipids composed of glycerol,
Two fatty acids, Phosphate group and Alcohol amine.
 2. Sphingophospholipids: backbone is sphingosine,
Sphingophospholipids composed of sphingosine
alcohol+ONE fatty acid+ phosphate+ choline.
 3. Both classes are found in membranes and play a
role in the generation of lipid-signaling molecules.

4. Glycerophospholipids : are formed from
phosphatidic acid (PA) and an alcohol.
 Serine + PA = phosphatidylserine (PS)
 Ethanolamine + PA =
phosphatidylethanolamine (cephalin)
 Choline + PA = phosphatidylcholine (lecithin)
PC
 Inositol + PA = phosphatidylinositol (PI)
 Glycerol + PA =phosphatidylglycerol (PG)

5. Sphingophospholipids or sphingomyelin
 The backbone of sphingomyelin is the amino alcohol
sphingosine, rather than glycerol.
 A long-chain fatty acid is attached to the amino group of
sphingosine through an amide linkage, producing a ceramide,
which serve as a precursor of glycolipids.
 The alcohol group at carbon 1 of sphingosine is esterified to
phosphorylcholine, producing sphingomyelin, the only
significant sphingophospholipid in humans.
 Sphingomyelin is an important componant of the myelin of
nerve fibers (myelin sheath) that insulates & protects neuronal
fibers of the central nervous system

6. Synthesis of Phospholipid
 In the biosynthetic process, one of the hydroxyls of the
phospholipid is first activated by attachment of a nucleotide,
cytidine diphosphate(CDP).
 The CDP is attached either to the diacylglycerol, forming an
activated phosphatidate, CDP-diacylglycerol (strategy 1), or to
the hydroxyl of the head group (strategy 2).
 In both cases, the CDP-bound structure is considered an
"activated intermediate," and CMP is released as a side
product of GP synthesis.
 A key concept in phosphoglyceride synthesis, is activation
either of diacylglycerol or the alcohol to be added by linkage
with CDP

8. Synthesis of PE and PC from
preexisting choline and ethanolamine
These synthetic pathways involve the phosphorylation
of choline or ethanolamine by kinases, followed by
conversion to the activated form, CDP-choline or CDP-
ethanolamine .
 Finally, choline-phosphate or ethanolamine-phosphate
is transferred from the nucleotide (leaving CMP) to a
molecule of diacylglycerol (see Figure 17.5).
Significance of choline reutilization : The reutilization
of choline is important because, whereas humans can
synthesize choline de novo, the amount made is
insufficient for our needs. Thus, choline is an essential
dietary nutrient with an adequate intake of 550 mg for
men and 420 mg for women.

10. Synthesis of phosphatidylethanolamine (PE) &
phosphatidylcholine (PC)
 PC & PE are most abundant phospholipids in eukaryotic cells.
 The primary route of synthesis uses choline and ethanolamine
obtained either from the diet or turnover of the body's
phospholipids. In the liver, PC also can be synthesized from
phosphatidylserine (PS) and PE.
 The liver requires a mechanism for producing PC, even when
free choline levels are low.
 To provide the needed PC, PS is decarboxylated to
phosphatidylethanolamine (PE) by PS decarboxylase.
 PE then undergoes 3 methylation steps to produce PC.
 S-adenosylmethionine (SAM) is the methyl group donor lead
to S-adenosylhomocysteine

12. Phosphatidylserine (PS)
 The primary pathway for synthesis of PS in
mammalian tissues is provided by the base
exchange reaction, in which the ethanolamine
of PE is exchanged for free serine.
 This reaction, although reversible, is used
primarily to produce the PS required for
membrane synthesis.

13. Phosphatidylinositol (PI)
 PI is synthesized from free inositol and CDP-
diacylglycerol.
 PI is an unusual phospholipid in that is often
contains stearic acid on carbon 1 and
arachidonic acid on carbon 2 of the glycerol.
 PI, therefore, serves as a reservoir of
arachidonic acid: in membranes and, thus,
provides the substrate for prostaglandin
synthesis when required.

15. Sphingolipids
 Sphingomyelin, a sphingosine-based phospholipid, is
a major structural lipid in the membranes of nerve
tissue.
 The synthesis of sphingomyelin is shown in Figure,
Briefly, palmitoyl CoA condenses with serine, as
coenzyme A and the carboxyl group (as CO2) of
serine are lost.
 This reaction, like the decarboxylation reactions
involving amino acids, requires pyridoxal phosphate
(a derivative of vitamin B6) as a coenzyme.

16.  The product is reduced in an NADPH-requiring reaction to
sphinganine, which is acylated at the amino group with one of
a variety of long-chain fatty acids, and then desaturated to
produce a ceramide--the immediate precursor of
sphingomyelin.
 A ceramide with a fatty acid thirty carbons long is a major
component of skin, and regulates skin's water permeability.
 Phosphorylcholine from phosphatidylcholine is transferred to
the ceramide, producing sphingomyelin and diacylglycerol.
 Sphingomyelin of the myelin sheath contains predominantly
longer-chain fatty acids such as lignoceric acid and nervonic
acid. whereas gray matter of the brain has sphingomyelin that
contains primarily stearic acid.

18. Functions of phospholipids
 In association with proteins phospholipids form the structural
components of membranes and regulate membrane permeability.
 They participate in the absorption of fats from the intestine.
 They are essential for the synthesis of different lipoproteins and
thus participate in transport of lipids.
 The prevent accumulation of fats in liver (lipotropic factors).
 They participate in the transport of cholesterol and thus help in
the removal of cholesterol from the body.
 They act as surfactants (respiratory distress syndrome).
 Cephalin participate in the blood clothing.
 Phosphotidyl inositol is the source of second messenger that are
involved in the action of some hormones.

19. Role of sphingolipids
 Abundant component of myelin sheath (25%
in humans).
 Also widely distributed in membranes of
plants (use phytosphingosine),and lower
eukaryotes(yeast).
 These lipids are in a continuous state of
turnover, defects in this metabolism leads to
various diseases.