CHEM 43: Biochemistry I - Lipids (PDF)

CHEM 43: Biochemistry I LIPIDS Overview of Lipids The steroid class of lipids (cholesterol) is found in biological membranes and used...

CHEM 43: Biochemistry I LIPIDS Overview of Lipids The steroid class of lipids (cholesterol) is found in biological membranes and used Lipids as a precursor for many hormones Greek word, lipos, which means “fat” Acts as thermal blanket and cushion compounds that are relatively insoluble in Function: water, but freely soluble in nonpolar organic solvents like benzene, chloroform, ether, hot Triglycerides - storage form of energy alcohol, acetone Phospholipids and cholesterol - structural components of biomembranes Unlike proteins (polymers of amino acid) or Steroid hormones and prostaglandins - DNA (polymers of nucleic acid), lipids are not metabolic regulators polymers of a specific mono unit due to their Amphipathic lipids - act as surfactants, diverse structure detergents, and emulsifying agents Characteristics: Acts as electric insulators in neurons Subcutaneous fat - provides insulation Water-insoluble compounds against changes in external temperature Soluble in non-polar solvents such as Pads of fat - protect internal organs by petroleum ether, benzene, chloroform providing a cushioning effect Found in biological systems Help in the absorption of fat-soluble Diverse Group of Biomolecules: vitamins (A, D, E, and K) Amphipathic – have a non-polar and polar Improve taste and palatability of food end Non-polar lipids (fats) are the principal molecules for energy storage Polar lipids (nitrogen and phosphorus containing) are components of biological membranes Prepared by: Mai  CHEM 43: Biochemistry I LIPIDS Classification of Lipids State at Type Note on SFA I. Storage or Neutral Lipids room temp A) Triacylglycerols (TAGs)/Triglycerides Saturated Solid (SFA) Consumption esters of glycerol and fatty acids must be no more than 10% of storage forms of fats in animals and humans Monounsatur Thick liquids total kilocalories ated (MSFA) or soft solids due to the risk of cardiovascular Structure disease Polyunsatura liquid ted (PSFA) Saturated Unsaturated Molecules that fit Have nonlinear closely together in a chains that do not regular pattern. allow molecules to pack closely. Strong attractions Have low melting between fatty acid points. chains. High melting points Are liquids at room make them solids at temperature Nomenclature: room temperature. Stearate | steric acid | C18:0 | n-octadecanoic acid 1. Saturated Fatty Acids General Structure: Systematic Names of Saturated FA Short Hand Common Systematic Notation Name Name Fatty Acid Component of TAGs/Triglycerides 1 Formic Methanoic Aliphatic carboxylic acids 2:0 Acetic Ethanoic Fatty acids usually in the cis conformation: Causes kink in the chain 3:0 Propionic Propanoic Rotation about other C-C bonds would 4:0 Butyric Butanoic permit a more linear structure 5:0 Valeric Pentanoic Number and Position of Double Bonds: Saturated: single C-C bonds 6:0 Caproic Hexanoic Unsaturated: double C=C bonds 8:0 Caprylic Octanoic Monosaturated: 1 double bond present Polyunsaturated: 2 0r more double bonds 10:0 Capric Decanoic The number of double bonds influences the physical nature of fatty acids: Prepared by: Mai  CHEM 43: Biochemistry I LIPIDS 12:0 Lauric Dodecanoic 14:0 Myristic Tetradecanoic 2. Unsaturated Fatty Acids Polyunsaturated Fatty Acids (PUFA) - essential fatty acids Mammals cannot synthesize the two main 2. Saponification types of polyunsaturated fatty acids: linoleic Hydrolysis of triglycerides by alkali/bases (omega-6) and linolenic (omega-3). Also known as soap formation Most prostaglandins are synthesized from arachidonic acid (a linoleic acid derivative). B) Waxes esters of fatty acids and high molecular weight monohydric alcohols simple esters of long-chain Waxes alcohols Glycerol and ester of glycerol Omega fatty acids Glycerides (mono glycerides, diglycerides and triglycerides) II. Membrane Lipids A) Phospholipids 1. Glycerophospholipids or Phosphoglycerides Esters of glycerol, fatty acids, phosphate, and a polar head group Reactions of Triglycerides 1. Hydrolysis This occurs in the body during dietary fat digestion and TAG mobilization from adipose tissue. Triglycerides in the body are hydrolyzed by enzymes called lipases Prepared by: Mai  CHEM 43: Biochemistry I LIPIDS Examples of Phosphoglycerides: Net charge Name Name of X Formula of X (at pH 7) Phosphatic acid - -1 Phosphatidylethanolamine ethanolamine 0 Phosphatidylcholine choline 0 Phosphatidylserine serine -1 Phosphatidylglycerol glycerol -1 Phosphatidylinositol-4,5-biphos myo-Inositol-4,5-biphosphat -4 phate e Cardiolipin phosphatidylglycerol -2 2. Sphingolipids Composed of sphingosine, fatty acids, Lactosylceramide Di-, tr-, or (a globoside) tetrasaccharide phosphate, and a polar head group Name Name of X Formula of X Complex Ganglioside GM2 oligosaccharide Ceramide - Sphingomyelin phosphocholine Neutral glycolipids Glucosyl- glucose cerebroside Prepared by: Mai  CHEM 43: Biochemistry I LIPIDS B) Archaeal ether lipids precursor to horme that Vitamin D regulates calcium metabolism antioxidant and promotes Vitamin E healing of damaged tissues III. Nonsaponifiable Lipids α-Tocopherol A) Terpenes Polymers of the isoprene unit blood-clotting co-factor Vitamin K Fat-soluble vitamins (A, D, E, K) (phylloquinone) furnishes visual pigment of B) Eicosanoids the vertebrate eye and Vitamin A 20-C compounds derived from arachidonate regulator of gene expression during epithelial cell growth Short-range signal molecules Alter activities both of the cells in which they are synthesized and of adjoining cells nature of effects may vary from one type of cell to another Prepared by: Mai  CHEM 43: Biochemistry I LIPIDS Examples of Eicosanoids: Cholesterol non–aliphatic, steroidal Prostaglandins built from four linked hydrocarbon rings Major classes are designated PGA through absent in prokaryotes PGI found in virtually all animal membranes absent in plant membranes Precursors of bile acids, steroid hormones, and Vitamin D Sources: diet: only found in animal fat biosynthesis: primarily synthesized in the Functions: liver from acetyl-CoA; biosynthesis is stimulate inflammation inhibited by LDL uptake regulate blood flow to particular organs degradation: only occurs in the liver control ion transport across membranes induce sleep Bile Acids derived from cholesterol C) Steroids detergent molecules secreted in bile from Numbering System: the gallbladder; assist in the absorption of dietary lipids in the intestine Bile Salts polar derivatives of cholesterol highly effective detergents – contain both polar and nonpolar regions Sterols synthesized in the liver, stored and Steroid alcohols concentrated in the gall bladder, and then released into the small intestine to solubilize dietary lipids Solubilization increases the effective surface area of lipids more surface area is exposed to the digestive action of lipases lipids more readily absorbed by the intestine Prepared by: Mai  CHEM 43: Biochemistry I LIPIDS Lipoprotein particles are classified according to Bile salts = major breakdown products of cholesterol increasing density: Chylomicrons very low-density lipoproteins (VLDL) Other steroids derived from cholesterol: intermediate-density lipoproteins (IDL) Testosterone (androgen) and estradiol low-density lipoproteins (LDL) (estrogen) mediate the development of high-density lipoproteins (HDL) sexual characteristics and sexual function in animals Progesterone – controls menstrual cycle and pregnancy Glucocorticoid (cortisol) – participates in the control of carbohydrate, protein and lipid metabolism Mineralocorticoids – regulate salt (Na+, K+, and Cl-) balances in tissues LDL HDL the major carrier of picks up cholesterol cholesterol in the released into the blood plasma from dying cells transports cholesterol to peripheral tissues Cholesterol shuttled to the liver for regulates cholesterol degradation by bile synthesis at these salts – Excreted sites Excess cholesterol is in the form of LDL IV. Lipoproteins Lipoproteins transport cholesterol and “bad” cholesterol “good” cholesterol triacylglycerols throughout the organism Lipoprotein particles consist of a core of The ratio of LDL, HDL used to evaluate hydrophobic lipids surrounded by a shell of susceptibility to the development of heart more polar lipids and apoproteins disease Protein components have 2 roles: For a healthy person, the LDL/HDL ratio is - solubilize hydrophobic lipids 3.5 - contain cell-targeting signals Prepared by: Mai  CHEM 43: Biochemistry I LIPIDS Biological Membranes Double bonds make it more difficult to pack Important for cell viability the chains together, making the lipid bilayer Composed of lipids, proteins, carbohydrates more difficult to freeze. Lipid components include: - PAGs (main) - Glycolipids - Steroids (cholesterol) Phospholipids are the major class of membrane lipids Some common phosphoglycerides found in membranes: Phosphatidyl serine Phosphatidyl ethanolamine Phosphatidylcholine Phosphatidyl inositol Movement in the Membrane Diphosphatidyl glycerol (cardiolipin) Archaeal Lipids Phosphoglyceride Sphingomyelin Archaeal lipid Structure of membranes: Membranes usually exist as lipid bilayers - Polar head groups in contact with H2O - The nonpolar tail lies in the interior Nonpolar HC tail may contain saturated or unsaturated fatty acids Bilayer held together by noncovalent interactions - e.g., Van der Waals forces Prepared by: Mai  CHEM 43: Biochemistry I LIPIDS Glycolipids in Membranes Usually sphingosine derivatives May contain 1 or more attached sugars - Usually, NAG or N-GalNAc Important in cell-cell recognition, intracellular signaling Membrane Proteins Integral Peripheral interact extensively with the bind to the surfaces Catalyzed Movement hydrocarbon region of the of integral proteins bilayer. traverse the lipid bilayer Cholesterol in Membranes Cholesterol: key regulator of membrane fluidity inserts into bilayers -OH group forms H-bond with –COO- of a PAG disrupts the regular interactions between fatty acyl chains Prepared by: Mai  CHEM 43: Biochemistry I LIPIDS Fluid Mosaic Model Selective Permeability of Cell Membrane membranes = 2D solutions of oriented lipids and globular proteins membranes = 2D solutions of oriented lipid bilayer has a dual role lipids and globular proteins - solvent for integral membrane proteins - permeability barrier Biological membranes are asymmetric Outer inner surfaces of all known biological membranes have different components, enzymatic activities Carbohydrates only on the ECM side In the RBC membrane, sphingomyelin and phosphatidylcholine are located in the outer layer (ECM) phosphatidyl ethanolamine and phosphatidyl serine are located in the inner layer (cytosol) cholesterol present in both layers General Factors Affecting Transport: Molecular size and shape Solubility in membrane environment - Membrane Asymmetry lipid solubility of the substance The asymmetrical distribution of Charge - degree of ionization phospholipids and glycolipids in the lipid bilayer of human RBCs Prepared by: Mai  CHEM 43: Biochemistry I LIPIDS Influential Characteristics of Chemicals a) Partitioning Distribution of a solute between 2 immiscible solvents at equilibrium Partition Coefficient Measure of the partitioning of a chemical between the 2 phases (lipid and aqueous phases) Depends on lipophilicity or hydrophobicity Higher coefficient, more permeable (DDT, Chemical Transport dioxin, PCBs) a) Passive Diffusion 𝐶𝐿 KQW or octanol-water No external energy is expanded 𝐾= 𝐶𝑊 partition coefficient At equilibrium, the net transfer is zero b) Water Solubility Polar groups: -OH, -NH2, -COOR (less permeable) Increased ionization (less permeable) c) Ionization Based on the partitioning theory Only non-ionized, nonpolar chemicals penetrate the membrane At equilibrium, the concentration of the non-ionized species is equal on both sides Features that favor diffusion: Ionized substances cannot penetrate membranes by simple diffusion Chemical Properties - Low molecular weight - Lipid solubility Transport Processes As determined by the chemical structure, non-polar molecules or non-ionized states. 3 general classes of transport systems: uniport (blue protein), Membrane Properties Antiport (green protein), and - Large surface area symport (orange protein). - Thin membrane High concentration of gradient Both antiport and symport are collectively called cotransport. Prepared by: Mai  CHEM 43: Biochemistry I LIPIDS b) Carrier Mediated Transport Active Transport (Proton Pump) May involve energy use (active: against the concentration gradient) or not (facilitated) Important for substances lacking sufficient lipid solubility Facilitated Transport Active Transport Driven by a Transport against concentration gradient concentration gradient No energy consumption, Requires energy still a passive process consumption b) Secondary Active Transport against the electrochemical gradient, Assisted by membrane Assisted by integral driven by ions moving down its gradient proteins membrane proteins (carrier may be specific (Carrier may be highly (e.g., transport of lactose) for the chemical) specific for the chemical) Transport of glucose in intestinal epithelial cells Active Transport a) Primary Active Transport transport is linked to the hydrolysis of ATP or other high-energy molecules (e.g., Na+/K+ ion pump) Prepared by: Mai