Basics of Biochemistry - 2 PDF

 Chemistry of lipids : o Lipids are a heterogeneous group of water-insoluble (hydrophobic) organic molecules o They can be extracted from tissues by nonpolar solvents o Transported in plasma in association with protein, as in lipoprotein particles  Biological Functions of Lipids: Cel...

 Chemistry of lipids : o Lipids are a heterogeneous group of water-insoluble (hydrophobic) organic molecules o They can be extracted from tissues by nonpolar solvents o Transported in plasma in association with protein, as in lipoprotein particles  Biological Functions of Lipids: Cell Membrane structure Storage of energy Insulation from environment Water repellent Signaling molecules, Paracrine hormones, Steroid hormones. Pigments, Color of tomatoes, carrots. Antioxidants, Vitamin E Cofactors for enzymes, Vitamin K  Deficiencies or imbalances of lipid metabolism: It can lead to some of the major clinical problems such as : - Obesity - Atherosclerosis  Fatty acids: They are aliphatic mono-carboxylic acids R-(CH2)n-COOH , "n" is mostly an even number of carbon atoms (4-36) longer fatty acids (>22 carbons) being found in the brain  Classification of fatty acids: A- Saturated Fatty Acids , 1- Short chain Saturated F.A. (2-10 carbon). Acetic F.A. (2 C ) CH3-COOH. 2- Long chain Saturated F.A. (more the10 carbon) palmitic(16 C) CH3-(CH2)14-COOH  B- Unsaturated Fatty Acids: 1. Monounsaturated, they contain one double bonds - Palmitoleic acid: CH3-( CH2 )5CH=CH-(CH2)7 –COOH double bond between C9-C10 2. Polyunsaturated (Essential fatty acids), - They cannot be synthesized in the human body. - They are required for normal growth and metabolism - Deficiency Essential fatty acid deficiency (rare) can result in a dry, scaly dermatitis as a result of an inability to synthesize molecules that provide the water barrier in skin - Linoleic: (2 double bonds) CH3-(CH2)4-CH = CH-CH2-CH=CH-(CH2)7-COOH  Nomenclature: IUPAC nomenclature: carboxyl carbon is C-1. Common nomenclature: α,β,γ,δ,ε etc. from C-1. Carbon farthest from carboxyl is ω.  C18:1Δ9 = oleic acid, C18:1(9) 18 carbon fatty acid with a double bond positioned at the 9th carbon (between carbons 9 and 10).  Trans fats However, they are produced by fermentation and are obtained from dairy products and meat They are produced during hydrogenation of f ish or vegetable oils which contain unsaturated fatty acids. They are bad to the health because they increase blood levels of LDL (bad cholesterol), decrease HDL (good cholesterol).  Melting points o At room temperature, the saturated fatty acids have a waxy consistency o Unsaturated fatty acids of these lengths are oily liquids Specific gravity of lipids 1. Simple lipids: (a) Fats and oils Types of triglycerides: 1-Simple triglycerides: 2-Mixed triglycerides:  Triacylglycerols Provide Stored Energy Cytosol Fat cells under skin , Mammary glands , Abdominal cavity  Triglyceridesvs polysaccharides as a storage fuel  Triacylglycerols Provide Insulation  Structural Lipids in Membranes; Membrane lipids are amphipathic Metabolism of lipids 1. Lipogenesis. 2. Synthesis of TAG. 3. Catabolism of TAG. 4. Fatty acid beta oxidation. 5. Ketogenesis and Ketone Bodies formation.  Catabolism of TAG: :  Catabolism of TAG: :  Fate of Glycerol  Fate of Glycerol  Fatty acid beta oxidation: The free fatty acids bind to albumin in the plasma. Fatty Acid Activation by esterification with CoASH. Membrane transport of fatty acyl CoA ester. Carbon Backbone Reaction Sequence: Dehydrogenation. Hydration. Dehydrogenation. Thiolase Reaction.  Activation of Fatty Acids:  Transport into Mitochondrial Matrix: carnitine palmitoyltransferase I carnitine palmitoyltransferase II o First, an acyl group is transferred from the cytosolic coenzyme A to carnitine by carnitine palmitoyltransferase I, an enzyme associated with the outer mitochondrial membrane o This reaction forms acylcarnitine, and regenerates free coenzyme A. o Second, the acylcarnitine is transported into the mitochondrion in exchange for free carnitine by translocase. o C arni t i ne pal mi t o yl t ransfe rase I I , an e nz yme o f t he i nne r mitochondrial membrane catalyzes the transfer of the acyl group from carnitine to coenzyme A in the mitochondrial matrix, thus regenerating free carnitine.  Fatty acid Beta oxidation: step 1  Fatty acid Beta oxidation: step 2  Fatty acid Beta oxidation: step 3  Fatty acid Beta oxidation: step 4   -Oxidation and ATP :  Activation of a fatty acid requires: 2 ATP  One cycle of oxidation of a fatty acid produces: 1 NADH → 3 ATP & 1 FADH 2 ATP. 2 →  Acetyl CoA entering the citric acid cycle produces: 1 Acetyl CoA 12 ATP. →  From one fatty acid ( ex,,,, n-10) ------- (n/2 - 1) NADH and FADH 2. (n/2) Acetyl-CoA  REGULATION OF β-OXIDATION:  Positive Effectors: - Low insulin and high glucagon (i.e. low insulin:glucagon ratio). - ADP.  Negative Effectors: - High insulin and low glucagon - High ATP.