Explain how the acetyl CoA molecules, the raw material for Fatty acids synthesis, is transferred to the cytoplasm from mitochondria? Acetyl CoA molecules combine with oxaloacetate in the mitochondria to form citrate Citrate moves from the mitochondria to the cytoplasm Citrate lyase cleave citrate back into acetyl CoA and oxaloacetate Describe the reaction catalyzed by Acetyl CoA carboxylase and explain how phosphorylation affects the activity of the Acetyl CoA carboxylase Acetyl CoA carboxylase activates acetyl CoA to malonyl CoA in the second stage of fatty acid synthesis (carboxylation step) This conversion is the committed step of fatty acid synthesis, so Acetyl CoA carboxylase is a key regulatory enzyme in fatty acid synthesis Phosphorylation of acetyl CoA carboxylase deactivates the enzyme → inhibits fatty acid synthesis AMP-activated protein kinase (AMPK) is essentially a fuel gauge Low energy charge tells AMP to phosphorylate acetyl CoA carboxylase → deactivates enzyme → inhibits fatty acid synthesis because energy charge is too low Remember, low energy charge favors catabolism (fatty acid oxidation) not anabolism (fatty acid synthesis) Case 10 Lecture Slides Lipids Rich in carbon and hydrogen Low in oxygen Insoluble in water (hydrophobic) Fatty acids are the simplest lipids Long chain hydrocarbons with a carboxylate group at one end Saturated - has no double bonds Solid at room temperature Unsaturated Monounsaturated - has 1 C=C Polyunsaturated - has > 1 C=C Lipids include Fatty acids Stored as triacylglycerol in adipocytes (adipose cells) Triacylglycerols (triglycerides) Triester made of one glycerol and 3 fatty acids (can be a mix of saturated and unsaturated Glycerol is a three-carbon alcohol with a hydroxyl group attached to each carbon A fatty acid consists of a carboxyl group attached to a long carbon skeleton Membrane lipids: phospholipids, glycoproteins, cholesterol Glycerol-phospholipid - diester that consists of one glycerol, 2 fatty acids (nonpolar tails), and one phosphate-amino alcohol (polar head) Steroid - contains four fused ring structures; 3 cyclohexane and 1 cyclopentane E.g. cholesterol Membrane phospholipids 3-carbon glycerol linked to a negatively charged phosphate group, and two fatty acids Major component of cell membranes due to their amphipathic nature (having both hydrophobic and hydrophilic parts) Trans fat (trans-unsaturated fatty acids) Adds hydrogen to unsaturated fats make them more solid Shown to be consistently associated with increased risk of coronary heart disease Raises levels of LDL (low-density lipoproteins) Lowers levels of HDL (high-density lipoproteins) Increases triglycerides in the bloodstream and promotes systemic inflammation May increase risk of alzheimer’s by up to 75% Good vs bad oil Liquid at room temperature = good oil Plant and fish oils (cis unsaturated) Solid at room temperature = bad oil Trans unsaturated fat Animal fats (saturated fats) The digestion of lipids is complicated by their hydrophobicity Stomach converts lipids into an emulsion, a mixture of lipid droplets and water Enhanced with the aid of bile salts, amphipathic molecules Lipases cleave triacylglycerols into free fatty acids and monoacylglycerol Fatty acid binding proteins (FABP) transport fatty acids and monoacylglycerol into intestinal cells Fatty acid transport proteins (FATP) transport fatty acids and monoacylglycerol to the smooth endoplasmic reticulum Triacylglycerols are resynthesized and packaged with phospholipids, cholesterol and proteins into chylomicrons Chylomicrons are released into the lymph system Fatty acids are processed in three steps Lipolysis - triacylglycerols are degraded to fatty acids and glycerol Lipases and water cleave the triacylglycerols Glycerol goes to the liver to enter gluconeogenesis or glycolysis Glycerol is absorbed by the liver and phosphorylated Dihydroxyacetone and D-glyceraldehyde 3-phosphate can enter glycolysis or gluconeogenesis Net production of ATP when one mole of glycerol is completely oxidized Cytosol Glycerol processing Enters: 1 glycerol, 1 ATP Exits: 1 dihydroxyacetone phosphate, 1 NADH Glycolysis Enters: 1 dihydroxyacetone phosphate, 1 NAD+, 2 ADP Exits: 1 pyruvate, 1 NADH, 2 ATP Mitochondria PDH Enters: 1 pyruvate Exits: 1 acetyl CoA, 1 NADH, 1 CO2 Citric acid cycle Enters: 1 acetyl CoA Exits: 1 ATP, 3 NADH, 1 FADH2, 2 CO2 Muscle ETC Enters: 3 FADH2, 4 NADH Exits: 4.5 + 10 = 14.5 ATP Heart and liver ETC Enters: 6 NADH, 1 FADH Exits: 15 + 1.5 = 16.5 ATP Muscle total 14.5 + 2 + 1 -1 = 16.5 ATP Heart and liver total 16.5 + 2 + 1-1 = 18.5 ATP Activation - fatty acids must be activated and transported into mitochondria for degradation Beta - oxidation - fatty acids and broken down in a step-by-step process into acetyl CoA, which enters the citric acid cycle
