Basic Biochemistry: Lipid Structure Dr. Kamal D. Mehta Department of Molecular & Cellular Biochemistry Wexner Medical Center at the Ohio State University

Learning Objectives Describe the structures and classification of lipids that play important roles in controlling biological processes. Recognize the structure of some common lipids of biological importance. Identify components of lipids molecules, such as fatty acids, glycerol, sphingosine, phosphate, organic bases, inositol, etc. Describe how do amphipathic lipid molecules interact in aqueous systems.

Learning Resources  Principles of Medical Biochemistry, by Meisenberg & Simmons  Essential Cell Biology (ECB), by Alberts et al., Pages 55,  Basic Medical Biochemistry, by Marks, Marks, & Smith, Pages 58-62

1. What are lipids?  Lipids are non-polar (hydrophobic) compounds. They are not soluble in water but are soluble in nonpolar solvents such as ether, choloroform, and benzene.  Lipids include fats, oils, steroids, and waxes.  Lipids are related by their physical rather than by their chemical properties.

2. Why do we need to study them?  BIOMEDICAL IMPORTANCE:  Required for membrane formation  An efficient source of energy  Fat content of nerve tissue is particularly high  Signaling molecules  Hormones  Obesity, and Atherosclerosis

3. How are they classified and what are their structures?  CLASSIFICATION OF LIPIDS:  Long chain aliphatic carboxylic acids  Triacylglycerols- Esters of fatty acids with glycerol  Glycerophospholipids- Esters of glycerol with fatty acids and phosphate derivatives  Glycolipids  Sphingolipids: Esters of fatty acids with sphingosine  Steroids- Polycyclic aliphatics  Prostaglandins and Leukotrienes-oxidized derivatives of C-20 fatty acids

A. Fatty acids: CH 3 (CH 2 ) n -COO - Non-polar Polar  Fatty acids consist of a hydrocarbon chain with a carboxylic acid at one end. About 40 different fatty acids are known naturally.  Most naturally occurring fatty acids have an even number of carbon.  In humans, fatty acids usually have 16 to 20 carbon atoms.  Saturated fatty acids and unsaturated fatty acids  Multiple sites of unsaturation are Polyunsaturated fatty acids, whereas a single site of unsaturation are Monounsaturated fatty acids.  Their fluidity decreases with chain length and increases according to degree of unsaturation.

Examples: 14:0 myristic acid 16:0 palmitic acid 18:0 stearic acid 18:1 cisD9 oleic acid 18:2 cisD9,12 linoleic acid 18:3 cisD9,12,15 linonenic acid 20:4 cisD5,8,11,14 arachidonic acid Examples of common fatty acids: Stearic acid (C18) Palmitic acid (C16) Oleic acid (C18)

Double bonds can be either cis or trans:  Naturally occurring unsaturated vegetable oils have almost all cis bonds but using oil for frying causes some of the cis bonds to convert to trans.  Trans fatty acids are carcinogenic

Double bonds creates a kink

Formation of an ester: R’OH+ HO-C-R” R’-O-C-R’’ + H 2 O O O Example: triacylglycerol O R’NH 2 + HO-C-R” R’-NH-C-R’’ + H 2 O Formation of an amide: O Example: fatty acids attached to proteins C Fatty acids bind to other molecules by amide or ester linkage

B. Triacylglycerols:  Animal Fats and Vegetable Oils:  Both are triacylglycerols (three fatty acids esterified with glycerol) (triglycerides)  Animal fats- Saturated and monounsaturated fatty acids  Oils- Mono and polyunsaturated fatty acids  More unsaturation leads to lower melting point  Function of fat and oil is storage for energy

Triacylglycerols consist of 3 fatty acids and glycerol O C OH CH 2 OH H Glycerol + 3 fatty acids

C. Phospholipids (Glycerophospholipids or Phosphoglycerides):  Glycerol plus two fatty acyl ester bonds- third position on glycerol is linked to phosphate which in turn esterified to another small molecule.  Plasma membrane is composed of proteins and lipids (50% by mass).

Phospholipids

Phosphatidylcholine (PC), Phosphatidylethanolamine, Phosphatidyl-serine (PS), Sphingomyelin (SM), are the major phospholipids in membrane.

D. Sphingolipids:  Esters of phosphate and small molecules with sphingosine.  Sphingomyelin, a ceramide with a phosphocholine or phosphoethanolamine head group, is a common constituent of plasma membranes.

Another major constituent of plasma membrane: Cholesterol  Amphipathic lipid and is an essential constituent of cell membranes.  Cholesterol is largely hydrophobic. It has one polar group, a hydroxyl.  It is the parent molecule from which all steroids in the body are synthesized.  Cholesterol modulates membrane fluidity. It restricts phospholipid movement and affects membrane fluidity.  Decreases the permeability of membrane to small water- soluble molecules.

Cholesterol

Cholesterol in Lipid Bilayer

Minor components of membrane: Glycolipids  Sphingosine based lipids containing carbohydrate instead of the phosphate ester.  They are found only in the outer leaflet of the plasma membrane.

Packing arrangements of lipid molecules in an aqueous environment

Three views of a plasma membrane

Membrane Model

Cholesterol immobilize the first few hydrocarbon groups of the phospholipid molecules. This makes the lipid bilayer less deformable and decreases its permeability to small water-soluble molecules. Without cholesterol a cell would need a cell wall. Cholesterol and the Lipid Bilayer

The influence of cis-double bonds in hydrocarbon chain

The assymetrical distribution of phospholipids molecules in the lipid bilayer of human red blood cells

Phosphpolipid mobility  The types of movements possible for phospholipid molecules in lipid bilayer.

In Summary  Lipids are hydrophobic and are related by physical characteristic rather than by chemical structure.  They perform different functions in the cell. For example, triglycerides stores energy whereas phospholipids are involved in membrane formation. Another constituent of the membrane cholesterol controls fluidity and block passage of small molecules.  Membrane bilayers have polar groups of phospholipids facing the aqueous environment whereas hydrophobic fatty acid chain is buried in the hydrophobic environment.  Proteins occupy this bilayer in an integral or peripheral manner.

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