STRUCTURE of LIPIDS


Introduction

Lipids are defined in terms of solubility, and not in terms of particular structures, as in the cases of proteins and nucleic acids.

Lipids associate with one another via van der Waals forces and the hydrophobic effect.

Lipids play three major biochemical roles:

1. as a storage form for metabolic energy (triglycerides)
2. as components of membranes
3. as messengers (prostaglandins, steroid hormones)


Examples of lipids:

Soaps and Detergents:

Soaps and detergents are called amphipathic molecules because they have a hydrophilic head group (either polar or charged) and a hydrophobic portion (usually alkyl side chains).

Soaps are the sodium or potassium salts of long-chain fatty acids.

Detergents form micelles, which are spherical bodies with hydrophilic portion of the molecules on the outside and the hydrophobic portion on the inside.


Triglycerides/Waxes:

Triglycerides are stored as a reserve of metabolic energy in fat cells and in the seeds of plants.

When the fatty acids that make up the major part of triglycerides are predominantly unsaturated, the triglycerides are called oils and are liquid at room temperature (examples are olive oil, corn oil, etc.). When the fatty acids are predominantly saturated, the lipid is a fat and is solid at room temperature (examples are butter, lard, etc.).

Waxes are the fatty acid esters of long-chain fatty alcohols, making them so hydrophobic that they repel water (as they do on the surfaces of leaves).

None of the lipids mentioned above are components of membranes.


Membrane lipids:

Membrane lipids form bilayers, and under special conditions, liposomes (or membrane vesicles).

Liposomes consist of an enclosed liquid volume surrounded by a spherical bilayer, and they are often used by biochemists for reconstitution studies of purified membrane proteins.

Membranes are made up of a variety of types of lipids, including glycerophospholipids, sphingolipids, and cholesterol.

Constituents:

Glycerophospholipids:

Glycerophospholipids comprise a group of lipids that share common structural aspects.

They contain a common core structure made up of two fatty acids, glycerol, and phosphate (referred to as phosphatidic acid) that is linked via an ester bond to an alcohol. The nature of the alcohol gives each lipid its name:

phosphatidylserine: composed of phosphatidic acid and the amino acid serine

phosphatidylethanolamine: composed of phosphatidic acid and ethanolamine (which can be derived from serine)

phosphatidylcholine: composed of phosphatidic acid and choline (which can be derived from ethanolamine via methylation)

phosphatidylinositol: composed of phosphatidic acid and inositol (which is really an alcohol, and not a sugar)


Sphingolipids:

Sphingolipids (named after the sphinx) have remained mystery lipid molecules until just recently because the study of their biological function has been so difficult.

The distinguishing mark of a sphingolipid is the presence of an unsaturated long-chain amino alcohol, most frequently a compound called sphingenine.

ceramide: sphingenine with a long-chain fatty acid attached to the amino group

sphingomyelin: ceramide + phosphocholine attached at terminal CH2OH

cerebrosides: a ceramide with a sugar at terminal CH2OH

ganglioside: a ceramide with a complex CHO structure (containing sialic acid) at terminal CH2OH

You may notice that many of these compounds have names drawn from portions of the nervous system, an indication of their abundance there.


Cholesterol:

Cholesterol is a tetracyclic alcohol containing 27 carbons that is derived from a C-5 isoprenoid precursor. It is important in membranes, and also as a precursor to detergent (bile) and as a precursor ro messenger molecules (steroid hormones).


Basic functions of membranes:

Membranes play a number of roles in biological systems:

compartmentation: they act as a boundary to keep chemical reactions localized.

concentration: they permit active transport to concentrate molecules and ions against an (electro) chemical gradient.

energy conversion: they make it possible for the electron transport chain to create a proton gradient, which can then be used to generate ATP.

information transfer: they can house receptor molecules (membrane proteins) for neurotransmitters, hormones, and cell-cell recognition.


Basic structure of a membrane:

thickness of a membrane bilayer: 6-10 nm

content of lipids and proteins: range from 25 % protein and 75 % lipids (myelin) to 75 % protein and 25 % lipid (mitochondria)

the membrane lipid portion acts as an insulator: specific resistance:

across membrane lipids: 1010 ohms/cm through the cytoplasm: 102 ohms/cm

asymmetric construction: both proteins and lipid types are disposed differently to each side (inside or outside) of the membrane.

The carbohydrate portion of glycoproteins and glycolipids are found on outside of the membrane; phosphatidylcholine and sphingomyelin, both containing quaternary amines, are more abundant in the outer half of the membrane bilayer.

Two types of membrane proteins:

a. peripheral membrane proteins are freed from the membrane by changes in ionic strength or pH. Once they are released, they are soluble in water.

b. integral membrane proteins are released from the membrane by dissolving the membrane in a non-ionic detergent. In order for these proteins to remain in solution they must reside in a detergent micelle or in a membrane vesicle (or a mixed detergent-lipid micelle).


Regulation of membrane fluidity:

Membrane fluidity is an important property of membranes because membrane proteins require a fluid (vs. crystalline) environment in order to function biochemically.

In procaryotes the length and degree of unsaturation of the fatty acids in phospholipids determines the degree of membrane fluidity.

In eucaryotes fluidity is influenced by the amount of cholesterol present in the membrane; cholesterol acts by preventing crystallization of membrane lipids.