Compound lipids:

Phospholipids Phospholipids are major structural

elements of biological membranes Structure

Glycerol + 2 fatty acids + phosphate group

A phospholipid is made up of the following: a hydrophilic head(Glycerol+

phosphate group) 2 hydrophobic tails (fatty acids) So they are amphipathic(polar lipids)

Phospholipids

Regarded as derivatives of phosphatidic acid , in which the phosphate is esterified with the —OH of a suitable alcohol.

They are amphipathic molecules containing a polar head and a hydrophobic portion

Amphipathic Nature Phospholipids are amphipathic- they have both hydrophobic and

hydrophilic portion in their molecule. Phospholipids form the bilayer

Cell membranes are phospholipid bilayers

Classification of Phospholipids

Classification of phospholipids

Based on nature of alcohol-

Glycerophospholipids-

Glycerol is the alcohol group.

• Phosphatidyl choline• Phosphatidyl

ethanolamine• Phosphatidyl serine• Phosphatidyl inositol• Phosphatidic acid• Cardiolipin• Plasmalogen

Sphingophospholipids-

Sphingol is the alcohol group

• Sphingomyelin

Glycerophospholipids

Also called phosphoglycerides

Membrane lipids in which,

two fatty acids are attached in ester linkage to the first and second carbons of glycerol

Third hydroxyl group of glycerol is esterified to phosphoric acid.

In addition a highly polar or charged group(second alcohol) is esterified to phosphoric acid.- referred as head alcohol group

Phosphatidylcholine or Lecithin

This is a nitrogen containing phospholipid.

Phosphoacylglycerols containing choline are the most abundant phospholipids of the cell membrane

Choline is important in nervous transmission (acetylcholine)

Lecithin –required for normal transport & utilization of other lipids

Absence causes fatty liver(accumulation lipid in liver-about 30%)- later to liver cirrhosis.

Phosphatidylcholine or Lecithin

The phosphoric acid is added to the third position, is further esterified to the quaternary nitrogen base, Choline.

Phosphatidylcholine or Lecithin

Complete hydrolysis of lecithin yields choline, phosphoric acid, glycerol & 2 FA.

Partial hydrolysis by Lecithinases (active principle of snake venum) yeilds lysolecithins.

Lysolecithins cause rapid rapture of RBC

2. Phosphatidyl ethanolamine or Cephalin

Cephalin differs from lecithin in that the nitrogen base ethanolamine or serine is present instead of choline.

Cephalin is also found in biomembranes and possesses amphipathic properties.

Brain and nervous tissue are rich in Cephalin

Cephalin (Phosphatidylethanolamine)

3. Plasmalogens

Constitute 10% of phospholipids of brain & muscles.

Strucurally similar to lecitin and cephalins but have the second

OH group is esterified by unsaturated ether.

Ethanolamine plasmalogen

3. Plasmalogens

The phosphoric acid is attached to choline or ethanolamine or serine

3 types

Phosphatidyl choline, phosphatidyl ethanolamine and phosphatidyl serine.

Phosphatidyl Ethanolamine

4. Phosphatidyl inositol Phosphatidic acid is esterified to inositol. Phosphatidyl inositol

bisphosphate or PIP2 is present in biomembranes.

This compound plays a vital role in the mediation of hormone action on

biomembranes and acts as a second messenger.

Classified as glycolipids , as they contain carbohydrate residue.

Phosphatidylinositol

5. Cardiolipin Diphosphatidylglycerol or cardiolipin : conatin two molecules

of phosphatidic acid are linked with a molecule of glycerol.

This is the only phospholipid with antigenic properties.

It is the major lipid of mitochondrial membrane. Commercially, it is extracted from myocardium.

Decreased cardiolipin level leads to mitochondrial dysfunction, and is accounted for-

– Heart failure,

– hypothyroidism and

– some types of myopathies.

Sphingolipids

Another class of lipids found frequently in biological membranes.

An 18-carbon amino alcohol, sphingosine forms the backbone of these lipids rather than glycerol.

In sphingolipids- sphingosine is attached to a fatty acid

through amide linkage to form a ceramide.

Sphingolipids

• Formation of an amide linkage between a fatty acid and sphingosine produces a ceramide.

• The fatty acid has a chain length varying from C18 to C24.

Sphingosine containing lipids

The sphingosine containing lipids may be of 3

types;

1. Sphingomyelins (Phosphosphingosides)

2. Glycosphingolipids and

3. Sulfatides.

SphingomyelinsIt represent a phosphorus-containing subclass of sphingolipids

(Phosphosphingosides)

Found in myelin sheath of nervous tissue of higher animals.

it is formed by the esterification of a phosphory lcholine or a phosphoryl ethanolamine to the 1-hydroxy group of a ceramide.

Sphingomyelin

Sphingomyelins

• A structure and a space-filling model of a choline sphingomyelin formed from stearic acid.

Glycosphingolipids

Glycosphingolipids (Glycolipids)They are seen widely in nervous tissues. This do not contain phosphoric acid;

instead they contain carbohydrates and ceramide.

When a single glucose or galactose is bound to ceramide, the molecule is a cerebroside Ceramide + Glucose →

Glucocerebroside Ceramide + Galactose →

Galactocerebroside

Sulfatide

Sulfolipids or Sulfatides:

These are formed when sulfate groups are attached to

ceramide oligosaccharides(galactose).

All these complex lipids are important components of

membranes of nervous tissue.

Widely distributed in plants

GangliosidesAre more complex glycosphingolipids, consist of a ceramide

backbone with three or more sugars esterified, one of these being a sialic acid such as N-acetylneuraminic acid (NANA).

These compounds are referred to as acidic glycosphingolipids, and they have a net negative charge at neutral pH.

They are present in nerve endings and appear to be important in nerve impulse transmission.

Gangliosides

Eicosanoids:

are local hormones produced by animal cells

Arachidonic acid and other polyunsaturated fatty acids are

used as precursor for their synthesis

They exert their effects at very low concentrations and

usually act near their sites of synthesisThese include Prostaglandins (PG), Thromboxanes

(Tx), Leukotrienes, and other hydroxyeicosanoic acids.

Prostaglandins

arachidonic acid is the precursor to prostaglandinsUlf von Euler(1930s) extracted prostaglandins from human

semenProstaglandins are formed from Arachidonate by Oxidation

and CyclizationBiosynthesis of prostaglandins is initiated by an enzyme

associated with the ER - Prostaglandin endoperoxide synthase (cyclooxygenase).

Prostaglandins are known to enhance inflammation in animal tissues.

Prostaglandins

Two groups of prostaglandins were originally defined: PGE,

for ether-soluble, and PGF, for phosphate buffer–soluble.

Each group contains numerous subtypes, named PGE1,

PGE2, and so forth…

Prostaglandins in a third group elevate body temperature

(producing fever) and cause inflammation and pain.

act in many tissues by regulating the synthesis of the

intracellular messenger 3,5-cyclic AMP (cAMP)

Prostaglandins

• Prostaglandin endoperoxide synthase, the enzyme that converts arachidonic acid to prostaglandin PGH2, possesses two distinct activities:

• cyclooxygenase (steps 1 and 2) and glutathione (GSSG)–dependent hydroperoxidase (step 3).

• Cyclooxygenase is the site of action of aspirin and many other analgesic agents

• tissue injury in which eicosanoid synthesis has been characterized include heart attack (myocardial infarction), rheumatoid arthritis, and ulcerative colitis.

“Take Two Aspirin and ….” Inhibit Your Prostaglandin Synthesis

• Acetylsalicylate (aspirin) inhibits the cyclooxygenase activity of endoperoxide synthase via acetylation (covalent modification) of Ser530.

• Aspirin exerts its powerful anti-inflammatory effect by inhibiting this first step in prostaglandin synthesis.

Prostacyclin 

Prostacyclin (also called prostaglandin I2 or PGI2) is a prostaglandin member of the family of lipid molecules 

It inhibits platelet activation and is also an effective vasodilator.

Prostacyclin (PGI2) chiefly prevents formation of the platelet plug involved in primary hemostasis

Leukotrienes•first found in leukocytes, contain three conjugated

double bonds. •They are powerful biological signals.• For example, leukotriene D4, derived from

leukotriene A4, induces contraction of the muscle lining the airways to the lung.

• Overproduction of leukotrienes causes asthmatic attacks.

• leukotriene synthesis is one target of antiasthmatic drugs such as prednisone

References:

1. Medicine Biochemistry 2nd edition by Garrett and Grisham

2. Lehninger Principles of Biochemistry Fourth Edition by David L.

Nelson and Michael M. Cox

3. Text book of biochemistry by DM Vasudevan and Sreekumari S

4. Color Atlas of Biochemistry Second edition,by Jan Koolman

and Klaus-Heinrich Roehm

5. Biochemistry the chemical reactions of living cells by David E.

Metzler.

Know Your Lipid Profile

Total Cholesterol < 200 mg/dl

LDL-Cholesterol < 100 mg/dl

HDL-Cholesterol ≥ 60 mg/dl

Triglycerides < 150 mg/dl

Fasting Blood Level Ideal, Healthy Level

Know Your Diabetes, Metabolic Risk

Blood Glucose < 110 mg/dl 110-125 mg/dl ≥ 126 mg/dl

2 hr GTT < 140 mg/dl 140-200 mg/dl > 200 mg/dl

Triglyceride < 150 mg/dl > 150 mg/dl Typically elevated

HDL ≥ 60 mg/dlM < 40 mg/dlF < 50 mg/dl

Typically low

Fasting Healthy Pre-Diabetes Diabetes (Metabolic Syndrome)

The Metabolic Syndrome

Abdominal Obesity Men Women

> 40 inch waist> 35 inch waist

Triglycerides ≥ 150 mg/dL

HDL cholesterol Men Women

< 40 mg/dL< 50 mg/dL

Blood Pressure ≥ 130/ 85 mm Hg

Fasting Blood Glucose 110-125 mg/dL

Know Your Blood Pressure

Category Systolic (mm/Hg) Diastolic (mm/Hg)

Normal 120 or less 80 or less

High Normal 130-139 85-89

High Blood Pressure 140 or more 90 or more

Strive for blood pressure of 120/80 or less