BIOSYNTHESIS OF PHOSPHOLIPIDS
Phospholipids:-
These are compounds containing, in addition to fatty acid and glycerol, phosphoric acid, nitrogenous bases, and another 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 ).
- CLASSIFICATION OF PHOSPHOLIPIDS:-
- Glycerophospholipids
- Spingophospholipids or Sphingomyelin
- SYNTHESIS OF PHOSPHOLIPIDS
- FUNCTIONS OF PHOSPHOLIPIDS
- FUNCTIONS OF SPHINGOLIPIDS
2. 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 ).
Phospholipid
3. Classification of Phospholipids
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
6. Synthesis of Phospholipid
1. In the biosynthetic process, one of the hydroxyls of the phospholipid
is first activated by attachment of a nucleotide, cytidine
diphosphate(CDP).
2. 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).
3. In both cases, the CDP-bound structure is considered an "activated
intermediate," and CMP is released as a side product of GP synthesis.
4. A key concept in phosphoglyceride synthesis, is activation either of
diacylglycerol or the alcohol to be added by linkage with CDP.
7.
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.
9.
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
11.
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.
14. 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.
15. • 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.
16.
17. 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.
18. 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.