Metabolism of phospholipids

• Phospholipids are a specialized group of

lipids performing a variety of functions.

• These include the membrane structure &

functions, involvement in blood clotting &

supply of arachidonic acid for the synthesis of

prostaglandins.

• Phospholipids are synthesized from

phosphatidic acid & 1,2-diacylglycerol,

intermediates in the production of

triacylglycerols.

• Phospholipids synthesis occurs in the smooth

endoplasmic reticulum.

• Inner mitochondrial membrane

• Phosphatidic acid is an important intermediate

in the synthesis of phosphoglycerides & TAG.

• The phosphatidic acid itself may be formed

from glycerol-3-phosphate or DHAP.

• The synthesis of glycerophospholipids can

occur either by activation into CDP-choline &

CDP-ethanolamine or by formation of active

diacylglycerol, CDP-diacylglycerol.

• It occurs mainly in liver & brain.

• Choline & ethanolamine first get

phosphorylated & then combine with CTP to

form, CDP-choline & CDP-ethanolamine.

• Phosphatidylcholine (lecithin) is synthesized

when CDP-choline combines with 1,2-

diacylglycerol.

• Phosphatidyl ethanolamine (cephalin) is

produced when CDP-ethanolamine reacts

with1,2-diacylglycerol.

• Phosphatidyl ethanolamine can be converted

to phosphatidyl choline on methylation.

• Phosphatidyl ethanolamine can exchange

its ethanolamine group with free serine to

produce phosphatidylserine.

• On decarboxylation, gives phosphatidyl

ethanolamine.

• CDP-diacylglycerol produced from

phosphatidic acid combines with inositol to

form phosphatidyl inositol (Pl).

• Phosphatidyl inositol contains arachidonic

acid on carbon 2 of glycerol which serves as,

a substrate for prostaglandin synthesis.

• PI is important for signal transmission across

membranes.

• CDP-diacylglycerol combines with glycerol 3-

phosphate to form phosphatidyl glycerol 3-

phosphate, which forms phosphatidylglycerol.

• The phosphatidylglycerol combines with

another molecule of phosphatidylglycerol to

produce cardiolipin.

• Cardiolipin possess antigenic properties.

• These are phospholipids with fatty acid at

carbon 1 bound by an ether linkage instead

of ester linkage.

• An important plasmalogen, 1-alkenyl 2-acetyl

glycerol 3 –phosphocholine, causes blood

platelet aggregation & is referred to as

platelet activating factor (PAF).

• These are phospholipids containing a

complex amino alcohol, sphingosine instead

of glycerol.

• Palmitoyl CoA & serine combine & undergo a

sequence of reactions to produce sphingosine

which is then acylated to produce ceramide.

• Sphingomyelin is synthesized when ceramide

combines with CDP-choline.

• Phospholipids are degraded by

phospholipases which cleave the

phosphodiester bonds.

• Four types of phospholipases.

• Phospholipase A1

• Phospholipase A2

• Phospholipase C

• Phospholipase D

• Phospholipase A1:

• It specifically cleaves the fatty acid at C1

position of phospholipids resulting in

lysophospholipid.

• These are further acted by

lysophospholipase, phospholipase B to

remove the second acyl group at C2 position.

• Phospholipase A2 hydrolyses the fatty acid at

C2 position of phospholipids.

• Snake venom & bee venom are rich sources

of phospholipase A2.

• Phospholipase A2 acts on phosphatidyl

inositol to liberate arachidonic acid, the

substrate for the synthesis of prostaglandins.

• Phospholipase C specifically cleaves the bond

between phosphate & glycerol of phospholipids.

• Phospholipase C is present in lysosomes of

hepatocytes.

• Phospholipase D hydrolyses & removes the

nitrogenous base from phospholipids.

• The degraded products of phospholipids enter

the metabolic pool & utilized for various

purposes.

• Lecithin-cholesterol acyltransferase (LCAT) is

plasma enzyme.

• Synthesized in liver.

• LCAT activity is associated with apoA1 of HDL.

• LCAT esterifies cholesterol by transferring acyl

group from the second position of lecithin.

• It is responsible for the reverse cholesterol

transport mediated by HDL

• HDL is a good cholesterol.

Lecithin + Cholesterol Lysolecithin + Cholesterol esterLCAT

• Sphingomyelinase of lysosomes hydrolyses

sphingomyelins to ceramide & phosphoryl

choline.

• Ceramide is further degraded to sphingosine &

free fatty acid.

Ceramide(sphingosine - FFA)

Phosphoryl cholineSphingomyelinase

Ceramidase

Action of sphingomyelinase & ceramidase on sphingomyelin

• Glycolipids are derivatives of ceramide

(sphingosine bound to fatty acid), commonly

called ad glycosphongolipids.

• The simplest form of glycosphingolipids are

cerebrosides containing ceramide bound to

monosaccharides.

• Galactocerebroside (Gal-Cer) &

glucocerebroside (Glu-Cer) are the common

glycosphingolipids.

• Galactocerebroside is present in nervous tissue.

• Glucocerebroside is an intermediate in

synthesis & degradation of glycosphingolipids

Sphingosine

Ceramide

Galactocerebroside Glucocerebroside

Galactocerebroside 3-sulfate

Acyl CoA

CoA

UDP-Glucose

UDP

UDP-Galactose

UDP

PAPS

Galactocerebroside

Ceramide

Sphingomyelin

Glucocerebroside Sphingosine

Galactose

β- Galactosidase

Ceramidase

Fatty acid

Choline -PSphingomyelinase

Glucose

β- Glucosidase

• Textbook of Biochemistry-U Satyanarayana

• Textbook of Biochemistry-DM Vasudevan

• Textbook of Biochemistry-MN Chatterjea