Lipids 2

Steven E. Massey, Ph.D.Assistant Professor of Bioinformatics

Department of Biology and Environmental SciencesUniversity of Puerto Rico – Río Piedras

Office & Lab:Bioinformatics Lab NCN#343BTel: 787-764-0000 ext. 7798

E-mail: stevenemassey@gmail.com

SphingolipidsSphingolipids are an additional type of membrane lipids, after glycerophospholipids, galactolipids and sulfolipids

They also have a polar head and two long alkyl tails, but theydo not contain glycerol, having sphingosine instead, whichis a long chain amino alcohol

They can fit into the categories of phosholipid or glycolipiddepending on the head group

Head group

Ceramide is the structural parent of all sphingolipids

Sphingomyelins contain phosphocholine, common in myelin

Glycosphingolipids are found on the outside of membranes 1) Cerebrosides are found in neural tissue and have a single sugar, while 2) globosides have two or more sugars. These are also known as neutral glycolipids, as they have no charge at pH 73) Gangliosides are the most complex sphingolipids and use oligosaccharides

Different types of sphingolipids

The structures of glycerophospholipids and sphingolipidsare similar:

Glycerophospholipid Sphingolipid

Sphingolipids are often recognition sites, found in neurons and on the surfaces of red blood cells

For example, glycosphingolipids are determinants of blood groups,with different oligosaccharide headgroups determining the blood types

Glycerophospholipids and sphingolipids are degraded in the lysosome so there is a constant turnover of membrane lipids

Degradation of lipids uses lipases - one for each hydrolyzable bond in a glycerophospholipid

The breakdown of sphingolipids is an important process, defects in this process will lead to serious illnesses

Eg. Tay-Sachs disease leads to developmental retardation,paralysis, blindness and early death

It is caused by the accumulation of ganglioside GM2 in the brain, resulting from a defect in its breakdown

Abnormal gangliosidedeposits in brainlysosomes

Sterols are structural lipids found in most eukaryotic cell membranes

The characteristic structure is called the steroid nucleus, which is four fused rings, 3 of them have 6 carbon atoms, the other one has 5 carbon atoms

Cholesterol is the major sterol in animal tissues and is amphipathic, with a polar head group (C3 hydroxy), and a nonpolar body (steroid nucleus and hydrocarbon chain at C17)

Sterols

Bile acids are derivatives of cholesterol that emulsifydietry fats and oils, acting as detergents in the intestine

Eicosanoids are fatty acid derivatives that act as paracrinehormones

Involved in reproductive function, inflammation, blood clotting and other processes

Derived from arachidonic acid, which is an omega 6 polyunsaturated fatty acid (20:4)

There are three classes of eicosanoids:ProstaglandinsThromboxanesLeukotrienes

Other functions of lipids: hormones, cofactors and pigments

Prostaglandins have a five membered ring and an array of functions eg. smooth muscle contractions during menstruation and child birth, wake-sleep cycle, fever,inflammation

Thromboxanes have a six membered ring with an internal ether group. Produced by platelets and are involved in blood clotting

Leukotrienes found in leukocytes and involved in contraction of smooth muscle eg. during breathing. Overproduction causes asthma

Non-steroidal anti inflammatory drugs (NSAIDs) inhibit the synthesis of thromboxane and prostaglandin from arachidonic acid

This can result in a reduction in fever

Common NSAIDs include aspirin, ibuprofen and paracetamol / acetaminophen

They can also result in reduction in clotting; this is beneficialin the case of cardiovascular disease – aspirin is used to 'thinthe blood' and prevent strokes, but is detrimental in the case of Dengue fever (never take aspirin or ibuprofen !!!!!!!!!)

Steroids

Steroids are oxidized derivatives of sterols, without the long alkyl chain

They include sex hormones (testosterone and estradiol) and adrenal hormones (cortisol and aldosterone)

Prednisone and prednisolone are steroid drugs that inhibit the synthesis of leukotrienes, prostaglandins and thromboxanes, by blocking arachidonic acid production

This reduces inflammation and they can be used for treatingallergies and asthma

Plant volatilesPlants produce thousands of different volatile substancesused in attracting pollinators, attracting protective organisms, communicating with other plants and repellingherbivores

Many are derived from fatty acids (eg. jasmonate, from jasmine, involved in plant defence to herbivores), or from condensation of 5 carbon isoprene units (eg. limonene, from limes)

Fat soluble VitaminsVitamins A, D, E and K are all fat soluble and are formed by condensation of isoprene units

A and D are hormone precursors

Vitamin D3 (cholecalciferol) is formed in the skin on exposure to light

Vitamin D regulates calcium uptake in the intestine and kidneys, deficiencycauses rickets

precursor vitamin D hormone

Vitamin A (retinol) in its different forms functions as a hormone important for growth of epithelial cells(retinoic acid) and is a visual pigment (retinal)

Carotene, found in carrots and other vegetables and fruits,is a good source of vitamin A

Vitamin E contains an aromatic ring and long isoprenoid chain. It functions as an antioxidant. Vitamin K is similar in structure and is involved in blood clotting

Many naturally occurring pigments are synthesized fromisoprene subunits. The alternating double bonds leads toelectron delocalization and absorbance of visible light

The following are carotenoids :

Working with lipids

It is necessary to use solvent to extract lipids fromcrude tissue extracts

Then, it may be separatedusing chromatographytechniques

TLC

After separation, gas-liquid chromatography (GC) or HPLC will separate the mixtures further

In GC stationary phase is liquid, while the mobile phase is gas

Mass spectrometry will reveal the complete lipid structure

Lipidomics is the attempt to catalog all lipids in a sample