Introduction to Lipids PDF

Introduction to Lipids  Structural relationship of the major classes of lipids Simplest lipids Contain or are derived from FAs What are Lipids? Heterogeneous group of water-insoluble organic molecules Because of insolubility in aqueous solutions lipid...

Introduction to Lipids  Structural relationship of the major classes of lipids Simplest lipids Contain or are derived from FAs What are Lipids? Heterogeneous group of water-insoluble organic molecules Because of insolubility in aqueous solutions lipids are found compartmentalized - membrane-associated lipids - droplets of TAGs in adipocytes - transported in plasma in association with protein e.g. lipoprotein particles  What are the functions of Lipids? Major source of energy Hydrophobic barrier Fat-soluble vitamins Coenzyme functions Hormones e.g. steroid and prostaglandins Protection of vital organs Vitamin carrier and hunger suppressor  Adults ingest about 81g of lipids /day More than 90% is normally triacyglycerol (TAG) The remainder of dietary lipids consists of - cholesterol - cholesterol esters - phospholipids - free (unesterified) fatty acids Some Common Lipids Hydrophobic portions are shown in orange Glycerophospholipid Fatty Acids What are they? Amphipathic molecules consisting of hydrophobic hydrocarbon tail with a terminal carboxyl group. The longer the chain the more hydrophobic the molecule What are they for? Fatty acids (FAs) exist Unesterified (free) in the body As fatty acyl esters e.g in Triacylglycerols (TAGs) Functions Can be oxidized by tissues (mostly liver and muscle) to provide energy Used by liver to produce ketone bodies Structural components of membrane lipids (Phospholipids)/glycolipids Lipids can act as signalling molecules Esterified FAs as TAG – major energy reserve in adipose tissue Serve as precursors of hormone-like compounds called prostaglandins Saturation of Fatty acids FA chains may contain no double bonds (saturated) or one or more double bonds (unsaturated) Double bonds are usually cis Cis bonds cause the tail to “kink” Membranes typically contain long chain fatty acids (LCFAs) – kinks help to maintain the membrane fluidity – changes in the FA composition can change the fluidity Chain Length and position of the double bonds Chain Length and position of the double bonds In Humans, FAs with even no predominate 16,18,20 FAs with >22 c usually found in the brain Nomenclature is important the C attached to the carboxyl group is called the -carbon The carbon of the terminal methyl group is called the -carbon The double bonds can be denoted relative to the  end e.g. arachidonic acid is called an -6 FA because the terminal double bond is 6 bonds from the  end What would that make Linolenic acid? Or linoleic acid? Triacylglycerol (TAG) Complex lipid comprised of 3 FAs and one molecule of glycerol FAs usually not the same Approx 90% of our dietary lipid Functions - Form in which lipid is stored in adipose tissue - Coalesce within WAT to form oily droplets which are nearly anhydrous – the major energy reserve of the body Question: Why is the design of the molecule well suited as storage form of energy? Why not use a carbohydrate as our main storage form of energy? PHOSPOLIPIDS What are they? Polar, ionic compounds composed of an alcohol that is attached to either a) Diacylglycerol (DAG) b) Sphingosine Amphipathic in nature – - hydrophilic head (Phosphate + alcohol) - Long hydrocarbon tail of FAs or FA-derived hydrocarbons  Phospholipids (PLs) Where do we find them? - The predominant lipids in cell membranes ALSO: Non membrane PLs - Components of lung surfactant - Essential component of bile Structure of Phospholipids 2 classes a) Those that have glycerol as a backbone - Glycerophospholipids b) Those that have sphingosine (an amino alcohol) as a backbone- Sphingophospholipids Glycerophospholipids - The major phospholipids - The predominant form in membranes - All contain or are derivatives of phosphatidic acid (PA) (DAG with a phosphate group on C-3) - PA is the simplest and is the precursor of the other forms Structural alterations result in a variety of subgroups 1. From phosphatidic acid and an alcohol e.g Phosphatidylserine , phosphatidyl choline, phosphatidylethanolamine 2. Cardiolipin – virtually exclusively found in inner mitochondrial membrane 3. Plasmalogens –ether glycerolphospholipid 4. Platelet-activating factor – triggers thrombotic and acute inflammatory events – one of the most potent bioactive molecules known (active conc 10-11 mol/l Sphingophospholipids Sphingomyelin – the only significant sphingophospholipid found in humans Backbone – amino alcohol – sphingosine Function – important component of the myelin sheath of nerve fibers  Isoprenoids Lipids derivatives of isoprene No! you do not need to know the structure of isoprene © 2014 John Wiley & Sons, Inc. All rights reserved.  Cholesterol is an isoprenoid Cholesterol is found in biological membranes. Metabolic precursor of steroid hormones – Estrogen and testosterone Has amphiphilic character © 2014 John Wiley & Sons, Inc. All rights reserved.  Steroids All structurally based on cholesterol 4 c-rings fused together Examples include the sex hormones estrogen, progesterone and testosterone 1. Phospholipid Degradation DEGRADATION OF PHOSHOLIPIDS - A) Phosphoglycerides - By Phospholipases – found in all tissues and pancreatic juice. - Also found in some toxins/venoms/pathogenic bacteria- dissolve cell membranes and facilitate infection - B) Sphigomyelin by sphingomyelinase  3. Biological membranes Niemann-Pick disease Rare genetic defect in sphingomyelinase which cleaves PC from sphingomyelin Sphingomyelin accumulates in brain, spleen and liver Becomes evident in infants and causes mental retardation and early death Commonly called Tay-Sachs disease Note: polar lipids of membranes undergo constant metabolic turnover  3. Biological membranes Niemann-Pick disease Defective degradation of Sphingomyelin Harmful accumulation in the spleen, liver, lungs, bone marrow, and the brain. In cells: accumulates in lysosomes to form fatty deposits with a foamy, swollen appearance http://www.ninds.nih.gov/disorders/niemann/niemann.htm Niemann Pick Tay Sachs MOI (mode of AR (Autosomal recessive) AR inheritance) Sphingomyelinase Hexosaminidase A Deficient enzyme Sphingomyelin GM2 (ganglioside) Accumulation Hepatosplenomegaly, Cherry red Cherry red macula (cherry- red spot on the retina of the Mental retardation Key Findings eye) Mental retardation Ashkenazi Jews Ashkenazi Jews Prevalence SO clinically HEPATOSPLENOMEGALY differentiates the 2