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 Phospholipids are major lipid constituents of cellular membranes. All the different phospholipids are synthesized from phospholipids acid. Phospholipids acid is precursor of all phospholipids except plasmalogen. Plasmalogen is synthesized from DHAP (derived from glucose via glycolysis). The various phospholipids are:

A. Classification of Phospholipids

1. Phosphatidylcholine (lecithin)    

2. Phosphatidylethanolamine (cephalin)

3. Phosphatidylserine            

4. Phosphatidylinositol

5. Cardiolipin (major lipids of mitochondrial membrane)


B. Phosphatidylcholines (Lecithins) Occur in Cell Membranes

Phosphoacylglycerols containing choline (Figure 15–8) are the most abundant phospholipids of the cell membrane and represent a large proportion of the body's store of choline. Choline is important in nervous transmission, as acetylcholine, and as a store of labile methyl groups.

Dipalmitoyl lecithin  is a very effective surface-active agent and a major constituent of the surfactant  preventing adherence, due to surface tension, of the inner surfaces of the lungs. Its absence from the lungs of premature infants causes respiratory distress syndrome.  Most phospholipids have a saturated acyl radical in the sn-1 position but an unsaturated radical in the sn-2 position of glycerol.


C.  Cardiolipin Is a Major Lipid of Mitochondrial Membranes

Phosphatidic acid is a precursor of phosphatidylglycerol which, in turn, gives rise to cardiolipin. This phospholipid is found only in mitochondria and is essential for mitochondrial function. Decreased cardiolipin levels or alterations in its structure or metabolism cause mitochondrial dysfunction in aging and in pathological conditions including heart failure, hypothyroidism and Barth syndrome (cardioskeletal myopathy).


These are shown below:

Fig: Phosphatidic acid and its derivatives. The O- shown shaded in phosphatidic acid is substituted by the substituents shown to form in A. 3-phosphatidylcholine, B. 3-phosphatidylethanolamine, C. 3-phosphatidylserine, D. 3-phosphatidylinositol, and E cardiolipin (diphosphatidylglycerol).


Fig: Plasmalogen


D. Sphingolipids

Sphingolipids are found in the Central Nervous System and particularly white matter

  1. Sphingomyelin: Sphingomyelin on hydrolysis yield a fatty acid, phosphoric acid, choline and a complex amino alcohol - sphingosine.

    The combination of sphingosine plus fatty acids is known as ceramide. See Figure below:

Fig: Sphingomyelin


Glycosphingolipids: Sphingolipids that contain carbohydrates moieties.   See Figure below:

Fig: Structure of galactosylceramide (galactocerebroside, R=H), & sulfogalactosylceramide (a sulfatide, R=SO42-)


  1. Cerebrosides are ceramide monohexosides (eg. galactocerebroside and glucocerebroside).
  2. Sulfatides are cerebrosides that contain sulphated sugars (β-sulfogalactocerebroside).
  3. Globosides are ceramide oligosaccharides that contain two or more sugar molecules, most often galactose, glucose or N-acetylgalactosamine, attached to ceramide.
  4. Gangliosides are glycosphingolipids that contain one or more neuraminic acid residues, usually N-acetyl derivative (i.e. NANA), which is sialic acids.
  5. Sphingolipidoses : are inherited genetic disorder referred to as lipid storage diseases, in which there is deficiency of an enzyme involved in in the normal catabolism, particular of sphingolipids.

Steroids: are lipids that contain four fused carbon rings that form the cyclopentanoperhydrophenanthrene steroid nucleus E.g. are Cholesterol, Steroids hormones


Table 24–1. Examples of Sphingolipidoses



Enzyme Deficiency

Lipid Accumulating

Clinical Symptoms

Tay-Sachs disease

Hexosaminidase A

Cer— Glc—Gal(NeuAc)GalNAc GM2 Ganglioside

Mental retardation, blindness, muscular weakness

Fabry's disease


Cer— Glc—GalGal Globotriaosylceramide

Skin rash, kidney failure (full symptoms only in males; X-linked recessive)

Metachromatic leukodystrophy

Arylsulfatase A

Cer— GalOSO3 3-Sulfogalactosylceramide

Mental retardation and psychologic disturbances in adults; demyelination

Krabbe's disease


CerGal Galactosylceramide

Mental retardation; myelin almost absent

Gaucher's disease


CerGlc Glucosylceramide

Enlarged liver and spleen, erosion of long bones, mental retardation in infants

Niemann-Pick disease


CerP choline Sphingomyelin

Enlarged liver and spleen, mental retardation; fatal in early life

Farber's disease


AcylSphingosine Ceramide

Hoarseness, dermatitis, skeletal deformation, mental retardation; fatal in early life

E.  Production of acetyl CoA and transport of acetyl CoA to cytoplasm

  1. Fatty acid synthesis depends on a cytoplasmic supply of acetyl CoA.
  2. Glucose is catabolized to acetyl CoA which combines with oxaloacetate to form citrate.
  3. Amino acids are also degraded to compounds that can enter the citric acid cycle to form citrate.
  4. Citrate is then transported across the mitochondrial membrane to the cytoplasm, where it is cleaved by citrate lyase enzyme as follows:

De Novo Synthesis of Fatty Acid

  1. This system is present in the soluble (cytosol) fraction of cells in many tissues e.g. liver, kidney, brain, lung, mammary gland and adipose tissue.
  2. Its cofactor requirements include NADPH, ATP, Mn2+, and HCO-3
  3. Acetyl CoA is the starting substrate, which is converted to malonyl CoA. Malonyl CoA is a donor for the 2 carbon fragments with the ultimate formation of palmitate (16-carbon fatty acid) as an end product.

G. Formation of malonyl CoA: 

Acetyl CoA Carboxylase is the regulatory enzyme of Fatty acid Synthesis.


Fatty Acid Biosynthesis



Extra Edge
  • The synthesis of long-chain fatty acids (lipogenesis) is carried out by two enzyme systems:  acetyl-CoA carboxylase and fatty acid synthase complex.
  • The pathway converts acetyl-CoA to palmitate and requires NADPH, ATP, Mn2+, biotin, pantothenic acid, and HCO3- as cofactors.
  • Acetyl-CoA carboxylase is a multienzyme protein and converts acetyl-CoA to malonyl-CoA.. Fatty acid synthase multienzyme complex, which is a dimmer of two identical polypeptide monomers each consisting of seven separate enzymatic activities and acyl carrier protein (ACP), catalyzes the formation of palmitate.
  • Fatty acid synthesis is performed in the cytoplasm of liver cells and to a lesser extent in adipose tissue cells.

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