JOY GHOSH

Lipids

Definition & Nature:

• Chemically diverse group of organic compounds.

• Insoluble/poorly soluble in water due to hydrocarbon chains (CH2-CH2-CH2-).
• Hydrophobic or amphipathic molecules.
• Origin:
• Carbanion-based condensations of ketoacyl thioesters.
• Carbocation-based condensations of isoprene units.

Classification:

• Simple Lipids:
• Yield 2 products on hydrolysis (e.g., fatty acids and glycerol).
• Complex Lipids:
• Yield 3 or more products on hydrolysis.

Types of Lipids:

• Fatty acids
• Phospholipids
• Sterols
• Sphingolipids
• Terpenes
• Others

Functions:

1. Storage of metabolic fuel.

2. Membrane structural components.
3. Protective roles in bacteria, plants, insects, and vertebrates.
4. Specialized functions:
• Pigments: Carotene
• Hormones: Vitamin D derivatives, sex hormones
• Signaling molecules: Eicosanoids, phosphatidylinositol derivatives
• Cofactors: Vitamin K
• Detergents: Bile salt

Fatty Acids:

• Simplest form of lipids.

1|Page
JOY GHOSH
• Structure: Long-chain hydrocarbons (12-24 carbons) with one carboxyl group.
• Even number of carbon atoms.
• Alkyl chain:

• Saturated or unsaturated.
• Unsaturated fatty acids mostly have cis configuration double bonds.
• Variations:
• Few contain three-carbon rings, hydroxyl groups, or methyl-group branches.
• Amphipathic: Have both non-polar and polar domains.

Key Points to Remember:

• Lipids are essential for energy storage, cell membrane structure, and protection.
• They play diverse and critical roles as hormones, pigments, signaling molecules, and
detergents.
• Fatty acids are the fundamental building blocks of more complex lipids and exhibit
amphipathic properties.

Figure 1.89 A fatty acid is a carboxylic acid that has a long aliphatic chain, which can be either saturated
or unsaturated. Most naturally occurring fatty acids have an unbranched hydrocarbon chain with an
even number of carbon atoms (commonly C-14 to C-24). We assign the number 1 (C-1) to the carboxyl
carbon and C-2 to the carbon next to it. In an older system, we refer to the second carbon in a fatty
acid as the a-carbon, the third carbon as the l-carbon, and the end methyl carbon as the w-carbon.

2|Page
JOY GHOSH

Saturated and Unsaturated Fatty Acids

Saturated Fatty Acids:

• No double bonds in the carbon chain.

• General formula: CH3-(CH2)n-COOH (n = number of methylene groups).
• Examples: Lauric, myristic, palmitic acids.
• Systematic Naming: Based on number of carbons and double bonds.
• Example: Stearic acid (18 carbons, no double bonds) = Octadecanoic acid (18:0).

Unsaturated Fatty Acids:

• One or more double bonds in the carbon chain.

• Types:
• Monounsaturated: One double bond.
• Polyunsaturated: Multiple double bonds.
• Double Bond Configuration: Typically cis (vs. trans).
• Bond Arrangement: Non-conjugated (alternating single and double bonds).
• Systematic Naming: Includes number of carbons, double bonds, and positions.
• Example: Oleic acid (18 carbons, one double bond) = Octadecenoic acid (18:1).
• Example: Linoleic acid (18 carbons, two double bonds) = Octadecadienoic acid (18:2).

Double Bond Position Designation Systems:

1. Carboxyl-Reference System:

• Numbering starts from the carboxyl terminus.

3|Page
JOY GHOSH
• Symbol: Δ followed by a superscript number indicating the double bond position.
• Example: Palmitoleic acid = 16:1; Δ9 (cis double bond between carbons 9 and 10).

2. Omega-Reference System:

• Numbering starts from the omega (last) carbon.

• Symbol: ω followed by the position number.
• Example: ω6 indicates a double bond on the sixth carbon from the omega end.

Essential Fatty Acids:

• Cannot be synthesized by animals; must be obtained through diet.

• Examples: Linoleate and linolenate.
• Limitation: Humans lack enzymes to introduce double bonds beyond C-9.
• Endogenously Synthesized Fatty Acids: Nonessential, not required from diet.

Key Points to Remember:

• Saturated fatty acids: No double bonds; generally solid at room temperature.

• Unsaturated fatty acids: One or more double bonds; generally liquid at room temperature.
• Essential fatty acids: Necessary from diet due to inability to synthesize.
• Nomenclature systems: Carboxyl-reference and omega-reference for double bond positions.

Triacylglycerol and Wax

Triacylglycerols (Triglycerides):

• Composition: Three fatty acids + one glycerol molecule.

• Types:
• Simple: One type of fatty acid.
• Mixed: Two or more different fatty acids.
• General Structure: Provided in Figure 1.90

Properties:

4|Page
JOY GHOSH
• Non-polar, hydrophobic.
• Major form of stored lipids.
• Neutral lipids: No charge due to covalent bonds between carboxyl groups of fatty acids and
glycerol.
• Fatty Acid Length: Varies; can be saturated or unsaturated.

Physical State:

• Fats: Solid at room temperature; high proportion of long-chain, saturated fatty acids.
• Oils: Liquid at room temperature; high proportion of unsaturated fatty acids.

Functions:

• Energy Reserves:
• Yield more energy per unit mass on oxidation compared to carbohydrates or proteins.
• Key energy source for hibernating animals and migrating birds.
• Storage: Synthesized and stored in adipocytes (fat cells).

Processes:

• Saponification:
• Hydrolysis of triacylglycerols with NaOH or KOH.
• Produces salts of free fatty acids (soap) and glycerol.
• Saponification Number: Milligrams of KOH required to saponify one gram of fat;
measures average molecular weight of fats.
• Iodine Number: Measures degree of unsaturation; grams of iodine added to 100-gram
sample of fat/oil.

Key Points to Remember:

• Triacylglycerols are crucial for energy storage and are differentiated by their fatty acid content
and physical state at room temperature.
• Saponification and iodine number are important metrics for understanding the properties
and composition of fats and oils.

Phospholipids

Phospholipids:

• Amphipathic molecules (both hydrophilic and hydrophobic regions).

• Components:
• Fatty acids

5|Page
JOY GHOSH
• Platform (Glycerol or Sphingosine)
• Phosphate group
• Alcohol attached to the phosphate

Phosphoglycerides (Glycerophospholipids):

• Derived from glycerol.

• Structure:
• Glycerol molecule
• Two fatty acids (attached to C-1 and C-2 of glycerol via ester bonds)
• Phosphate group (attached to C-3 of glycerol)
• Alcohol (e.g., choline, serine, ethanolamine, glycerol, inositol) attached to the phosphate
group
• Most numerous phospholipids in cell membranes.

Specific Types of Phosphoglycerides:

• Phosphatidic Acid: Simplest form; glycerol + two fatty acids + phosphate.

• Phosphatidylcholine (Lecithin): Glycerol + two fatty acids + phosphate + choline.
• Phosphatidylserine: Glycerol + two fatty acids + phosphate + serine.

Key Points to Remember:

• Phospholipids are essential components of cell membranes due to their amphipathic nature.
• Phosphoglycerides are a major class of phospholipids derived from glycerol.
• Alcohol moieties in phosphoglycerides determine the specific type (e.g., choline for
phosphatidylcholine).

Additional Visual Aid:

Phosphoglyceride Structure:

1. Glycerol Backbone:
• C-1: Fatty acid
• C-2: Fatty acid
• C-3: Phosphate group
2. Phosphate Group: Attached to C-3 of glycerol.
3. Alcohol Group: Attached to the phosphate (e.g., choline, serine).

This structure is crucial for forming the lipid bilayer in cell membranes, providing both structural
integrity and fluidity.

6|Page
JOY GHOSH

Ether Glycerophospholipids, Sphingophospholipids, and Glycolipids

Ether Glycerophospholipids:

• Key Feature: Ether linkage at C-1 position of glycerol (no acyl group).
• Common Example: Platelet Activating Factor (PAF)
• Functions: Causes platelet aggregation, dilates blood vessels.
• Types:
• Saturated ether-linked chain
• Double bond between C-1 and C-2
• Plasmalogen: Alkyl molecule that is cis-α,β-unsaturated.

Sphingophospholipids:

• Derived from sphingosine (18-carbon amino alcohol).

• Structure:
• Sphingosine backbone instead of glycerol.

7|Page
JOY GHOSH
• Ceramide: Formed by an amide linkage between a fatty acid and sphingosine.
• Sphingomyelin:
• Phosphocholine or phosphoethanolamine attached to C-1 hydroxyl.
• Functions: Present in plasma membranes, prominent in myelin sheath around nerve cell
axons.

Glycolipids:

• Contain saccharide groups (no phosphate).

• Types of Glycosphingolipids:
• Cerebrosides: Single monosaccharide linked to ceramide.
• Globosides: Oligosaccharide linked to ceramide.
• Gangliosides: Complex oligosaccharides with one or more residues of sialic acid.
• Sialic Acid: Derivatives of neuraminic acid (9-carbon backbone).
• Function: Gangliosides give a negative charge at pH 7.
• Series: GM (mono-sialic acid), GD (di-sialic acid), etc.
• Number of Gangliosides: More than 60 characterized.

Key Points to Remember:

Ether Glycerophospholipids:

• Ether linkage at C-1.

• PAF is a notable signaling molecule.

Sphingophospholipids:

• Sphingosine backbone.
• Ceramide forms the base of all sphingolipids.
• Sphingomyelin is vital for membrane structure and nerve function.
8|Page
JOY GHOSH
Glycolipids:

• Sugar-containing lipids without phosphate.

• Glycosphingolipids are major membrane lipids.
• Gangliosides: Important for cell recognition and signaling; provide a negative charge.

Steroids and Eicosanoids

Steroids:

• Basic Structure:

• Derived from triterpenes.

• Composed of four fused rings (steroidal nuclei).

• Sterols:

• A subclass of steroids with a hydroxyl group at C-3.

• Cholesterol:
• Essential component of animal cell membranes.
• Precursor for steroid hormones and bile salts.
• Stored as fatty acid ester in cells.
• Plant Sterols:
• Stigmasterol, sitosterol, campesterol.
• Fungal Sterol:
• Ergosterol.

9|Page
JOY GHOSH
Eicosanoids:

• Origin:

• Derived from 20-carbon polyunsaturated fatty acids (eicosanoic acids), especially

arachidonic acid.

• Function:

• Potent biological signaling molecules.

• Act as local hormones (short-range messengers).

• Pathways:

• Cyclooxygenase (COX) Pathway:

• Produces prostaglandins, prostacyclin, and thromboxanes.
• Lipoxygenase Pathway:
• Produces leukotrienes.

• Prostaglandins:

• Identified in human semen.

• Present in almost all mammalian cells (except RBCs).
• Derived from prostanoic acid (20-carbon fatty acid with a cyclopentane ring).

• Nomenclature:

• Prostaglandins (PG): Designated by "PG" followed by a letter (A-I) indicating the nature
of substituents on the cyclopentane ring.
• Numerical Subscript: Indicates the number of double bonds in the aliphatic chains.

• Synthesis:

• Precursor: Arachidonic acid (20-carbon, 5,8,11,14-eicosatetraenoic acid).

• Enzyme: Cyclooxygenase (COX), also known as prostaglandin G/H synthase.
• Process:

10 | P a g e
JOY GHOSH
• Initiation by plasma membrane phospholipids.
• COX catalyzes the introduction of oxygen and cyclization at C-8 and C-11.

Key Points to Remember:

Steroids:

• Four fused rings structure.

• Sterols like cholesterol are crucial for cell membrane integrity and as precursors for other
biologically significant molecules.

Eicosanoids:

• Local hormones derived from arachidonic acid.

• Two major pathways for their synthesis (COX and lipoxygenase).
• Prostaglandins, a type of eicosanoid, are involved in various physiological processes and are
found in almost all mammalian cells.

11 | P a g e
JOY GHOSH
Prostaglandins, Thromboxanes, and Leukotrienes

Prostaglandins:
• Immediate Precursor: Prostaglandin H2 (PGH2).
• Synthesis Enzymes:
• COX-1: Constitutively expressed in most mammalian tissues.
• COX-2: Induced by inflammatory stimuli, leading to increased prostaglandin levels that
cause inflammation.
• Functions:
• Stimulate uterine contraction.
• Lower blood pressure.
• Cause vasodilation.
• Mediate inflammation.
• Inhibition by NSAIDs:
• Aspirin (acetylsalicylate): Irreversibly inhibits COX by acetylating a serine residue,
reducing prostaglandin synthesis and inflammation.
• Ibuprofen: Reversibly inhibits COX by binding non-covalently to the active site.
• Selective NSAIDs (coxibs): Target only COX-2, reducing inflammation without affecting
COX-1 functions.
Thromboxanes:
• Conversion: Prostaglandins are converted to thromboxanes by thromboxane synthase in blood
platelets.
• Functions:

• Vasoconstriction.
• Stimulate platelet aggregation (initial step in blood clotting).
• Structures:
• Thromboxane A (TXA): Unstable bicyclic oxygenated ring.
• Thromboxane B (TXB): Stable oxane ring.
Prostacyclins:
• Synthesis: Generated from PGH2 by prostacyclin synthase, especially in endothelial cells.
• Functions:

• Vasodilation.
• Inhibit platelet aggregation.
• Promote differentiation and inhibit proliferation in vascular smooth muscle cells.
Leukotrienes:
• Synthesis Pathway: Lipoxygenase pathway from arachidonic acid.
• Primary Source: Leukocytes.
12 | P a g e
JOY GHOSH
• Classes:

• Chemoattractant LTB: Contains only hydroxyl moieties.

• Cysteinyl Leukotrienes: Contain amino acid moieties.
• Functions: Involved in inflammation and allergic reactions.
• Mechanism:
• Bind to G protein-coupled receptors (GPCRs).
• Effects:
• Activation of G proteins increases intracellular calcium or decreases intracellular
cAMP.

Plasma Lipoproteins

Overview:
• Function: Transport triacylglycerols, phospholipids, cholesterol, and cholesterol esters in the
blood.
• Structure:

• Core of neutral lipids (triacylglycerols, cholesterol esters).

• Monolayer coat of phospholipids and cholesterol.
• Embedded proteins (apolipoproteins) and cholesterol.

13 | P a g e
JOY GHOSH
Types of Lipoproteins:
• Classified by Density:

• Chylomicrons:
• Lowest density.
• Function: Transport dietary triacylglycerols and cholesterol from the intestines to
other tissues.
• Very Low-Density Lipoproteins (VLDL):
• Second lowest density.
• Function: Transport triacylglycerols from the liver to peripheral tissues.
• Intermediate-Density Lipoproteins (IDL):
• Intermediate density.
• Function: Intermediate in the conversion of VLDL to LDL.
• Low-Density Lipoproteins (LDL):
• Second highest density.
• Function: Deliver cholesterol to cells throughout the body; often referred to as
"bad cholesterol" due to its association with atherosclerosis.
• High-Density Lipoproteins (HDL):
• Highest density.
• Function: Collects cholesterol from the body's tissues and returns it to the liver;
known as "good cholesterol" due to its role in reducing cholesterol levels.
Key Points to Remember:
• Lipoproteins are essential for lipid transport in the blood due to the insolubility of lipids in
plasma.
• Apolipoproteins play a crucial role in the structure and function of lipoproteins.
• Density classification is based on the ratio of lipids to proteins (higher protein content =
higher density).

14 | P a g e
JOY GHOSH

15 | P a g e
JOY GHOSH

16 | P a g e