Lipids 2 Steven E. Massey, Ph.D. Assistant Professor of Bioinformatics Department of Biology and Environmental Sciences University of Puerto Rico Río Piedras Office & Lab: Bioinformatics Lab NCN#343B Tel: 787-764-0000 ext. 7798 E-mail: stevenemassey@gmail.com
Sphingolipids Sphingolipids are an additional type of membrane lipids, after glycerophospholipids, galactolipids and sulfolipids They also have a polar head and two long alkyl tails, but they do not contain glycerol, having sphingosine instead, which is a long chain amino alcohol Head group They can fit into the categories of phosholipid or glycolipid depending on the head group
Different types of sphingolipids 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 7 3) Gangliosides are the most complex sphingolipids and use oligosaccharides
The structures of glycerophospholipids and sphingolipids are 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 head groups 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 ganglioside deposits in brain lysosomes
Sterols 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)
Bile acids are derivatives of cholesterol that emulsify dietry fats and oils, acting as detergents in the intestine
Other functions of lipids: hormones, cofactors and pigments Eicosanoids are fatty acid derivatives that act as paracrine hormones 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: Prostaglandins Thromboxanes Leukotrienes
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 beneficial in the case of cardiovascular disease aspirin is used to 'thin the 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 treating allergies and asthma
Plant volatiles Plants produce thousands of different volatile substances used in attracting pollinators, attracting protective organisms, communicating with other plants and repelling herbivores 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 Vitamins Vitamins 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, deficiency causes 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 from isoprene subunits. The alternating double bonds leads to electron delocalization and absorbance of visible light The following are carotenoids :
Working with lipids It is necessary to use solvent to extract lipids from crude tissue extracts Then, it may be separated using chromatography techniques TLC
After separation, gasliquid 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