Lipids

Lipid

Organic molecule which is not soluble in water but is soluble in organic solvents

CH3(CH2)nCOOH

Functions

1. Energy

2. Insulation

3. Creams

4. Birds: feathers

5. Plants: coats leaves

6. Hormones and vitamins: precursor

7. Plasma membrane

8. In organs

9. In blood

Classification of lipids

1. Fatty acids and their derivatives

2. Glycerides: Neutral esters of fatty acids and glycerols

3. Phospholipids: Ionic esters of fatty acids, glycerols and phosphoric acid

4. Spingolipids: Lipids without glycerols

5. Glycolipids: lipids combined with proteins

Fatty acids

Hydrophilic polar carboxylic group and hydrophobic nonpolar hydrocarbon group.

1. Saturated: solid and waxy at room temp. [(CnH2n+1)COOH]. Contain only single double bonds. Most present in esterified form with glycerols (that are not are called FFA's). Palmitic acid C16:0

2. Unsaturated: Contain at least 1 double bond. Lower melting point. More soluble. Liquid at room temp.

Unsaturated fatty acids

1. MUFA: contain only one double bond. Oleic acid C18:1 □1

2. PUFA: -Dienoic series; contain 2 double bonds. Linoleic acid C18:2 □9,12 (Omega 6) M.P is -5

   -Trienoic series; contain 3 double bonds. a-Linoleic avid C18:3 □9,12,15 (Omega 3) M.P is -10

   -Tetranoic series; contain 4 double bonds. Arachidonic acid C20:4 □5,8,11,14. M.P is -50

   -Pentatonic series; contain 5 double bonds. Eicosapentanoic acid C20:5 □5,8,11,14,17

   -Hexanoic series; contain 6 double bonds. Docosahexanoic acid C22:6 □4,7,10,13,16,19. M.P is -50

Essential fatty acids

Cannot be produced in human and animal bodies.

Plant desaturase enzymes are capable to provide double bonds at □12 and □15 positions which are not possible by animal desaturase enzymes. Saturated fatty acids are biosynthesized first than double bonds are introduced later in various positions. Human and animal systems cannot introduce double bonds beyond the □9 position.

Fatty acd derivatives

Arachidonic acid C20:4 □5,8,11,14

1. Prostaglandins: synthesize in all mammalian cells excpeted RBC. Circulating hormones containing diverse groups such as keto, carboxyl, hydroxyl which are found on the side chain or cyclopentane ring in the structure. Double bonds in Trans configuration. Natural mediator of pain, fever and inflammation.

2. Thromboxane (TX): 1st isolated from blood platelets. Has 6-membered ring containing ether. Act in formation of blood clots and reduction of blood flow to the site of the blood clot.

3. Leukotrienes (LT): found in the WBCs and contains 3 conjugated double bonds. Result in contraction of smooth muscles. (LTC4)

Reactions of fatty acids

1. Esterification: one molecule of acid and one molecule of alcohol react reversibly to yield one molecule of water and an Ester.

2. Hydrogenation: When H2 is added across the double bond on unsaturated fatty acids catalyzed by Ni, Pt, Pd. Cis since both H2 attack double bond simultaneously. Used to test for unsaturated fatty acids and to produce margarine.

3. Ozonolysis: one of the ozone (O3) can join with a double bond of an unsaturated fatty acid and initially forms an unstable ozonide with a final product of two aldehydes

4. Oxidation by KMnO4: Neutral pH (each double bond of an unsaturated fatty acid can be oxidized to form cis-Diol). Alkaline pH (double bonds can be oxidized to form mono/di-carboxylic acid)

5. Oxidation by OsO4: Alkaline pH (oxidized to form cis-Diol)

Isomers

1. Geometrical: orientation of hydrocarbons around double bond. Cis and Trans

2. Positional: no. of isomers a fatty acid has depend on the position of double bond and number of carbon atoms

Glycerides

Neutral esters of fatty acids and glycerols

Ester of fatty acids and tri-hydric alcohols = acylglycerol or glycerides

1. Monoacylglycerol(glyceride): only one fatty acid molecule esterified with anyone of the carbon of tri-hydric alcohol

2. Diacylglycerol(glyceride): 2 fatty acid molecules are esterfied with any 2 carbon of tri-hydric alcohol

3. Triacylglycerol(glyceride): When 3 same/different fatty acid molecules are esterified with a tri-hydric alcohol. Most widely available neutral lipid (95%)

Phospholipid

Ionic Ester of fatty acid and glycerol

Polar head and non polar tail. Generally saturated fatty acids esterfied with the carbon 1&2 and unsaturated fatty acids with carbon 2 of glycerol molecule. Phosphoric acid binds with the hydroxyl group of carbon 3 and a base is linked with the phosphoric acid molecule

Class of phospholipids

1. Lecithin: most abundant in Biological membranes. Phosphatidylcholin.

2. Cephalin: present mainly in CNS. Principal in bacteria. Contains ethanolamine base in their structure and chemically called phosphatidyl ethanolamine.

3. Phosphatidylserine: originally found in bovine brain. Present in inner membrane and beneficial to quick recover from exercise injury. Contains a serin amino acid as a base = phosphatidyl serine.

4. Lipositols: widely distributed in brain tissue, bacteria and soybean oil. Present in inner side of cell membrane. Phosphorylated forms of phosphatidylinositol are called phosphoinositides and play important role in lipid signaling, cell signaling and membrane trafficking. Contains a myo-inositol as a base = phosphatidyl inositol.

5. Plasmalogens: present in brain and heart tissue. Fatty acid chain in carbon 1 of glycerol is replaced by an a-Ɓ-unsaturated ether. It may contain choline, ethanolamine or serine as it’s base

Sphingolipids

Lipids without glycerol.

Major membrane component. Most derivatives of C18 amino alcohol (sphingosine) whose double bond has the Trans configuration. N-acetyl derivatives of spingosine known as Ceramide.

Mainly composed of: Long chain fatty acids. Long chain amino alcohols. Polar head group of a phosphate and a base

1. Spingomyelin: phosphoryl choline derivative of ceramide. Mainly located in the nerve tissues but also found in blood. Abundant in myelin sheath

Clinical correlation, spingomyeline

1. Niemann Pick Disease: inherited absence of sphingomyelinase (enzyme that hydrolyzes sphingomyelin to form ceramide and phosphoryl) leading to extra lipids being deposited in our body. Foam cells store in lungs, liver, brain. Symptoms: Swelling of endothelial, mesenchymal and parenchymal cells of liver, speed, brain, bone marrow. Mental retardation, early death. Treatments: None.

2. Multiple sclerosis: autoimmune disease, immune system attacks CNS leading to plaques and lesions formation in the myelin sheath followed by demyelination. Symptoms: Fatigue, cognitive impairment. Lack of co-ordination. Abdominal discomfort. Treatment: None

Glycolipids

Carbohydrates + lipids. Normally present in the outer surface of the cell membrane. Also present in myelin sheath of CNS and spinal cord.

1. Cerebrosides: most abundant in myelin sheath nerves. Mainly combination of monosaccharides and ceramides. Classified as Glucocerebrosidase and Galactocerebrosidase. Further addition of monosaccharides to glucocerebrosides converts to more complex glycosphingolipids like blood group antigens.

2. Gangliosides: mainly located in the basal ganglion cells of CNS. Also present in the plasma membrane of the many extraneural cell types. Looks like cerbrosides but in addition to D-glucose or D-Galactose several other carbohydrates such as NAc-Glc, NAc-Gal and N-acetyl Neuraminic acid are also attached

Clinical correlation, cerebrosides

Lipid storage disease due to inherited deficiency of glucocerebrosidase enzyme. Glucocerebroside cannot be broken to cerebroside and glucose results in these lipids being deposited into several organs. Symptoms: Megaly, Hypersplenism, Liver cirrhosis, mental retardation. Treatments: Enzyme replacement, Organ transplantation, blood transfusion, gene therapy and antibiotics

Clinical correlation, gangliosides

1. Tay Sach's Disease: inherited disorder characterized by early death. Lack of hexaminidase A, involved in the Degradation of GM2 gangliosdie. Symptoms: Mental retardation and paralysis. Cherry spot on eye = blindness. Treatments: Gene therapy. Substrate reduction therapy. Enzyme replacement therapy.

2. Induction of diarrhea

3. Inhibition of protein synthesis: diphtheria toxin

4. Influenza

5. Cell to cell recognition

Other lipids

1. Waxes: Ester of fatty acids and alcohols.

2. Terpenes: derivatives of isoprene (5 carbon containing hydrocarbon with 2 double bonds).

3. Steroids: 3 six-membered ring and 1 five-membered ring in structure. Precursor = perhydrocyclopentanophenanthrene

4. Cholestrol: 27carbon in its fused ring with OH at position C3. Highly hydrophobic and widespread in Biological membranes.