BCM - lipids

Definition of lipids

• Lipids are as broad group of naturally occurring molecules including fats, waxes, sterols, fat-soluble vitamins, monoglycerides, diglycerides, phospholipids, and others

• May be broadly defined as hydrophobic or amphipathic small molecules; the amphipathic nature of some lipids allows them to form structures e.g. vesicles, liposomes, or membranes in an aqueous environment

Lipid bilayer in water - types of intermolecular forces

• Water-water - hydrogen bonds, electrostatic forces

• Water-head group - hydrogen bonds, electrostatic forces

• Tail-tail - London dispersion forces (stronger if tails are long, unbranched and saturated)

Glycerophospholipids

• 2 fatty acids are covalently linked to glycerol via ester bonds

• The fatty acids can be saturated or unsaturated

•  The third OH group of glycerol is bound to the ‘head group’ of the lipid (phosphocholine in this example)

Longer fatty acids have melting points than shorter ones

• melting point increases by ~10C per C2 unit

• Fatty acids have an even number of C atoms because they are synthesised form C2 units

• All saturated fatty acids are solids in their pure form at room temp 

Saturated fatty acids have higher melting points than unsaturated ones

• The biggest drop in melting point is caused by the first double bond

• This is because the double bonds are in the cis configuration, the tails become kinked and do not pack as well as the straight saturated tails - this makes the solid state less stable

• Unsaturated fatty acids are liquid in their pure form at room temp

Fatty acid nomenclature

Most dietary fats are triglycerides 

• butter, coconut oil and palm oil are solids because of their high content of saturated fatty acids - olive oil and rapeseed oil are liquids

Trans fats

• In food production, liquid vegetable oils are hydrogenated to produce saturated fats with a higher melting temperature and longer shelf life

• Partial hydrogenation of unsaturated fats converts some of the cis double bonds into trans double bonds

• Dietary intake of trans fats is linked to an increased risk of coronary artery disease

Types of head groups in glycerophospholipids

Cardiolipins 

• contains three glycerol molecules, one in each of the phosphotidylglycerol units and another one linking the units together

• First isolated form cow hearts, hence the name

• Makes up ~20% of the inner mitochondrial membrane

• Essential for the function of enzymes involved in oxidative phosphorylation

Reversible phosphorylation of phosphatidylinositol

• PI kinase = phosphatidylinositol kinase, i.e. an enzyme that transfers a phosphate group from ATP onto the inositol group

• PIP kinase = phosphatidylinositol 4-phosphate kinase, i.e. an enzyme that transfers a phosphate group from ATP onto the inositol 4-phosphate group

Cleavage of phosphoinositides generates second messengers

• Signalling pathways involving cleavage of phosphoinositides -> acetylcholine triggering the release of amylase in the pancreas

• Phospholipase C-B is activated by a signal molecule e.g. acetylcholine binding to a receptor protein on the cell surface - the important info is that the head group of PIP2 is cleaved by an enzyme to release the second messenger IP3

Sphingolipids are a major second class of lipids

• Myelin sheaths surround the axons of nerve cells and acts like the insulation around an electrical wire - the myelin sheath is the plasma membrane of Schwann cells, wrapped around the axon in multiple layers

• Sphingosine backbone replaces glycerol and one fatty acid

• Sphingosine + fatty acid = ceramine

• Sphingosine + fatty acid + phosphocholine = sphingomyelin

Glycolipids have important functions in the nervous system

• Gangliosids make up 6% of all lipids in the nervous system

• The sugar groups project from the plasma membrane and facilitate interactions with proteins and other cells

• Gangliosides are a characteristic component of lipid rafts

• All gangliosides contain at least one sialic acid group

Asymmetric distribution of lipids in the plasma membrane

• Phosphatidylserine is excluded from the outer leaflet by an active process - a flippase

•  Exposure of phosphatidylserine on the cell surface is a pro-apoptotic signal

A 3rd major class of lipids contain isoprenyl units

• Terpenes are hydrocarbons formally derived from the condensation of isoprene units

• Terpenoids are modified terpenes containing oxygen atoms, but the distinction is often not made, and all 3 terms are used interchangeably

• e.g. of isoprenoids are cholesterol, steroid hormones, and retinal

Cholesterol has complex effects on membrane fluidity

• Rigid steroid rings stiffen the membrane, it becomes less fluid above the transition temperature

• They also interfere with the crystallisation of fatty acid chains, preventing a sharp freezing below the transition temperature

Lipoproteins

•  because of their limited solubility in water, lipids are transported by the circulation as micelle-like particles

• Core - triglycerides and cholesteryl esters

• Coating - protein, phospholipid and cholesterol

Archaea have unique lipid membranes

• Other lipids apart from archaeol have head groups and/or double bonds in the tails

• The ether linkages make archaeal lipids resistant to hydrolysis in extreme conditions

• Methanopyrus kandleri grows at temperatures up to 122 C in hydrothermal vents

Isoprenylation of cysteins anchors intracellular proteins to membranes

Lipopolysaccharides in the outer membrane of Gram-negative bacteria

• because of their toxicity lipopolysaccharides are also called endotoxins