Lipids are a class of biological molecules defined by low solubility in water and high solubility in nonpolar solvents. As molecules that are largely hydrocarbon in nature, lipids represent highly reduced forms of carbon and, upon oxidation in metabolism, yield large amounts of energy.

LIPIDS AND MEMBRANES

Fatty acids occur in large amounts in biological systems, but rarely in the free, uncomplexed state. They typically are esterified to glycerol or other backbone structures.

• Definition: water insoluble compounds• Most lipids are fatty acids or ester of fatty acid• They are soluble in non-polar solvents such as petroleum ether, benzene,

chloroform• Functions

Upon oxidation in metabolism, yield large amounts of energy.Energy storage (38 KJ/g) (proteins and carbohydrates yield only about 17 kJ/g)

• Structure of cell membranes• Thermal blanket and cushion• Precursors of hormones (steroids and prostaglandins)

• Types:• Fatty acids• Neutral lipids• Phospholipids and other lipids

Fatty acids

Tail

Head

Ionized underphysiological conditionsGeneral structure – CH3-(CH2)n-COOH:

(Hydrophilic)

(Hydrophobic)

polarNon-polar

Fatty acids are carboxylic acids with long-chain hydrocarbon chains

Are rarely 'free' (uncomplexed) in nature

The carboxyl group has a pKa of 4-5 Is charged at neutral pH values

Estrutura de ácidos gordos

saturated unsaturated

Fatty acids are either saturated (all carbon–carbon bonds are single bonds) or unsaturated (with one or more double bonds in the hydrocarbon chain; mono or polyunsaturated)

C16 C18 C18 �9

C1

C18 �9, 12 C18 �9, 12, 15 C18 �5, 8, 11,14

Unsaturated fatty acids

Double bond is alwayscis in natural fatty acids.This lowers the meltingpoint due to “kink” inthe chain

C18:1 cis �9

There is free rotation about C-C bonds in the fatty acid hydrocarbon, except where there is a double bond.

Each cis double bond causes a kink in the chain.

As shown the cis bonds cause a "kink" or bend in the FA chain. Because of these kinks, unsaturated FAs are unable to pack as closely together as can saturated FAs. (They are prevented from packing due to van der Waals radii.) This produces flexible, fluid membranes and aggregates.

a rigid 30°bend inthe hydrocarbon chain of unsaturated fatty acids that interfereswith packing in space.

Most of the fatty acids found in nature have an even number of carbon atoms (usually 14 to 24).

Structures and melting points of some common fatty acids

Triacylglycerols

Triacylglycerols are a major energy reserve and the principal neutral derivatives of glycerol found in animals. These molecules consist of a glycerol esterified with three fatty acids

Adipocytes or fat cells (oil droplets)

Glycerol + fatty acid Fat + water

Dehydratation synthesis

Lipids: Mostly Carbon and Hydrogen; little Oxygen

In most glycerophospholipids (phosphoglycerides), Pi is in turn esterified to OH of a polar head group (X): e.g., serine, choline, ethanolamine, glycerol, or inositol.

The 2 fatty acids tend to be non-identical. They may differ in length and/or the presence/absence of double bonds.

Phospholipids

�fatty acids are esterified to hydroxyls on C1 & C2�the C3 hydroxyl is esterified to Pi.

Amphipathic lipids in association with water form complexes in which polar regions are in contact with water and hydrophobic regions away from water.

Depending on the lipid, possible molecular arrangements:

� Various micelle structures. E.g., a spherical micelle is a stable configuration for amphipathic lipids with a conical shape, such as fatty acids.

� A bilayer. This is the most stable configuration for amphipathic lipids with a cylindrical shape, such as phospholipids.

liquid crystal crystal

In the liquid crystal state, hydrocarbon chains of phospholipids are disordered and in constant motion.

At lower temperature, a membrane containing a single phospholipid type undergoes transition to a crystalline statein which fatty acid tails are fully extended, packing is highly ordered, & van der Waals interactions between adjacent chains are maximal.

Kinks in fatty acid chains, due to cis double bonds, interfere with packing in the crystalline state, and lower the phase transition temperature.

Membrane fluidity:The interior of a lipid bilayer is normallyhighly fluid.

Cholesterol, an important constituent of cell membranes, has a rigidring system and a short branched hydrocarbon tail. Is present in all animal tissues, and particularly in neural tissue. It is a major constituent of cellular membranes, in which it regulates fluidity

Cholesterol is largely hydrophobicbut it has one polar group, a hydroxyl, making it amphipathic.

Cholesterol is a major component

of the cell’s plasma membrane

(structural function), but it is also

the precursor for the key hormones

testosterone & estrogen

Cholesterol inserts into bilayer membranes

Cholesterol inserts into bilayer membranes with its hydroxyl group oriented toward the aqueous phase & its hydrophobic ring system adjacent to fatty acid chains of phospholipids.

The OH group of cholesterol forms hydrogen bonds with polar phospholipid head groups.

Interaction with the relatively rigidcholesterol decreases the mobility of hydrocarbon tails of phospholipids.

• Cholesterol:– 90% is found in cell membranes– Produced by the liver– Associated with cardiovascular

disease– Produced by animals only. None

found in plants.

Funções das membranas1. Barreira Selectiva

a) Rodeiam as células mantendo os enzimas e metabolitos no interiorb) Compartimentalização celular: definem organelos

2. Contêm sistemas enzimáticos – metabolismo energético (fosforilação oxidativa, fotossintese, ...)

3. Contêm sistemas de transporte – transporte de moleculas para o interior e manutenção da concentração iónica

4. Contêm locais de reconhecimento específico – eg.hormonas

As membranas biológicas são compostas por:1. Lipidos – a dupla camada lipídica cria uma barreira hidrofóbia

(maioritariamente fosfolípidos, glicolípidos e colesterol).

2. Proteínas – conferem específicidadea) proteinas periféricas ligadas à superfícieb) proteinas integrantes da membrana c) glicoproteinas

Quatro dos fosfólipidos mais abundantes em membranas de mamíferos

Rotation

Caudas hidrocarbonadas insaturadas possuem dobras que impedem as moleculas de se empacotarem perfeitamente aumentando a fluidez das membranas.

Cholesterol embeds among the fatty acids

Cholesterol (green) restricts the motility of the fatty acid tails of the phospholipids

Proteínas integrais da membrana atravessam a camada bilipídica

numa conformação de hélice alpha, na qual os grupos hidrofílicos formam pontes de H entre si, enquanto os grupos laterais

hidrofóbicos dos aminoácidos se projectam para o exterior da hélice,

contactando com as caudas hidrocarbonadas das moléculas

lipídicas.

Estrutura de proteínas membranares

polar Non-polar

Estrutura de proteínas membranares – hélices α

Lipid rafts

Microdomains of membranes relatively enriched in cholesterol and sphingolipids with saturated fatty acidsLipid rafts are less fluid than the surrounding membrane and enriched in certain proteins