Fatty Acid Oxidation

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fatty acid oxidation

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<ul><li><p>Fatty Acid Oxidation</p><p>Molecular Biochemistry II</p></li><li><p>A 16-C fatty acid with numbering conventions is shown.</p><p>Most naturally occurring fatty acids have an even number of carbon atoms.</p><p>The pathway for catabolism of fatty acids is referred to as the b-oxidation pathway, because oxidation occurs at the b-carbon (C-3).</p><p>C</p><p>O</p><p>O</p><p>-</p><p>1</p><p>2</p><p>3</p><p>4</p><p>a</p><p>b</p><p>g</p><p>C</p><p>O</p><p>O</p><p>-</p><p>1</p><p>2</p><p>3</p><p>4</p><p>a</p><p>b</p><p>g</p><p> EMBED ChemDraw.Document.4.5 </p><p>fatty acid with a cis-9 </p><p>double bond</p>_1008576813.cdx_1008576919.cdx_965825676.cdx</li><li><p>Triacylglycerols (triglycerides) are the most abundant dietary lipids. They are the form in which we store reduced C for energy. </p><p>Each triacylglycerol has a glycerol backbone to which are esterified 3 fatty acids </p><p>Most triacylglycerols are mixed. The 3 fatty acids differ in chain length &amp; number of double bonds.</p><p>H</p><p>2</p><p>C</p><p>H</p><p>C</p><p>H</p><p>2</p><p>C</p><p>O</p><p>H</p><p>O</p><p>H</p><p>O</p><p>H</p><p>H</p><p>2</p><p>C</p><p>H</p><p>C</p><p>H</p><p>2</p><p>C</p><p>O</p><p>O</p><p>O</p><p>C</p><p>R</p><p>O</p><p>C</p><p>C</p><p>R</p><p>O</p><p>R</p><p>O</p><p>H</p><p>O</p><p>C</p><p>R</p><p>O</p><p>H</p><p>2</p><p>C</p><p>H</p><p>C</p><p>H</p><p>2</p><p>C</p><p>O</p><p>H</p><p>O</p><p>H</p><p>O</p><p>H</p><p>H</p><p>2</p><p>C</p><p>H</p><p>C</p><p>H</p><p>2</p><p>C</p><p>O</p><p>O</p><p>O</p><p>C</p><p>R</p><p>O</p><p>C</p><p>C</p><p>R</p><p>O</p><p>R</p><p>O</p><p>H</p><p>O</p><p>C</p><p>R</p><p>O</p><p> glycerol fatty acid triacylglycerol</p><p> EMBED ChemDraw.Document.4.5 </p>_977227313.cdx_977227727.cdx_1008575693.cdx_977227399.cdx_977163222.cdx</li><li><p>Lipid digestion, absorption, transport will be covered separately. </p><p>Lipases hydrolyze triacylglycerols, releasing 1 fatty acid at a time, yielding diacylglycerols, &amp; eventually glycerol. </p><p>H</p><p>2</p><p>C</p><p>H</p><p>C</p><p>H</p><p>2</p><p>C</p><p>O</p><p>H</p><p>O</p><p>H</p><p>O</p><p>H</p><p>H</p><p>2</p><p>C</p><p>H</p><p>C</p><p>H</p><p>2</p><p>C</p><p>O</p><p>O</p><p>O</p><p>C</p><p>R</p><p>O</p><p>C</p><p>C</p><p>R</p><p>O</p><p>R</p><p>O</p><p>H</p><p>O</p><p>C</p><p>R</p><p>O</p><p>H</p><p>2</p><p>C</p><p>H</p><p>C</p><p>H</p><p>2</p><p>C</p><p>O</p><p>H</p><p>O</p><p>H</p><p>O</p><p>H</p><p>H</p><p>2</p><p>C</p><p>H</p><p>C</p><p>H</p><p>2</p><p>C</p><p>O</p><p>O</p><p>O</p><p>C</p><p>R</p><p>O</p><p>C</p><p>C</p><p>R</p><p>O</p><p>R</p><p>O</p><p>H</p><p>O</p><p>C</p><p>R</p><p>O</p><p> glycerol fatty acid triacylglycerol</p><p> EMBED ChemDraw.Document.4.5 </p>_977227313.cdx_977227727.cdx_1008575693.cdx_977227399.cdx_977163222.cdx</li><li><p>Glycerol, arising from hydrolysis of triacylglycerols, is converted to the Glycolysis intermediate dihydroxyacetone phosphate, by reactions catalyzed by:</p><p> 1 Glycerol Kinase </p><p> 2 Glycerol Phosphate Dehydrogenase. </p><p>C</p><p>H</p><p>2</p><p>C</p><p>H</p><p>C</p><p>H</p><p>2</p><p>O</p><p>H</p><p>H</p><p>O</p><p>O</p><p>P</p><p>O</p><p>3</p><p>-</p><p>C</p><p>H</p><p>2</p><p>C</p><p>H</p><p>C</p><p>H</p><p>2</p><p>O</p><p>H</p><p>H</p><p>O</p><p>O</p><p>H</p><p>C</p><p>H</p><p>2</p><p>C</p><p>C</p><p>H</p><p>2</p><p>O</p><p>H</p><p>O</p><p>P</p><p>O</p><p>3</p><p>-</p><p>O</p><p>C</p><p>H</p><p>2</p><p>C</p><p>H</p><p>C</p><p>H</p><p>2</p><p>O</p><p>H</p><p>H</p><p>O</p><p>O</p><p>P</p><p>O</p><p>3</p><p>-</p><p>C</p><p>H</p><p>2</p><p>C</p><p>H</p><p>C</p><p>H</p><p>2</p><p>O</p><p>H</p><p>H</p><p>O</p><p>O</p><p>H</p><p>C</p><p>H</p><p>2</p><p>C</p><p>C</p><p>H</p><p>2</p><p>O</p><p>H</p><p>O</p><p>P</p><p>O</p><p>3</p><p>-</p><p>O</p><p> glycerol glycerol-3-P dihydroxyacetone-P</p><p> EMBED ChemDraw.Document.4.5 </p><p>ATP ADP</p><p> H+ + </p><p>NAD+ NADH</p><p>1</p><p>2</p>_977171398.cdx</li><li><p>Free fatty acids, which in solution have detergent properties, are transported in the blood bound to albumin, a serum protein produced by the liver. </p><p>Several proteins have been identified that facilitate transport of long chain fatty acids into cells, including the plasma membrane protein CD36. </p><p>C</p><p>O</p><p>O</p><p>-</p><p>1</p><p>2</p><p>3</p><p>4</p><p>a</p><p>b</p><p>g</p><p>C</p><p>O</p><p>O</p><p>-</p><p>1</p><p>2</p><p>3</p><p>4</p><p>a</p><p>b</p><p>g</p><p> EMBED ChemDraw.Document.4.5 </p><p>fatty acid with a cis-9 </p><p>double bond</p>_1008576813.cdx_1008576919.cdx_965825676.cdx</li><li><p>Fatty acid activation: </p><p>Fatty acids must be esterified to Coenzyme A before they can undergo oxidative degradation, be utilized for synthesis of complex lipids, or be attached to proteins as lipid anchors. </p><p>Acyl-CoA Synthases (Thiokinases) of ER &amp; outer mitochondrial membranes catalyze activation of long chain fatty acids, esterifying them to coenzyme A.</p><p>This process is ATP-dependent, &amp; occurs in 2 steps. </p><p>There are different Acyl-CoA Synthases for fatty acids of different chain lengths. </p></li><li><p>Acyl-CoA Synthases </p><p>Exergonic PPi (P~P) hydrolysis, catalyzed by Pyrophosphatase, makes the coupled reaction spontaneous. </p><p>2 ~P bonds of ATP are cleaved. </p><p>The acyl-CoA product includes one "~" thioester linkage.</p><p>N</p><p>N</p><p>N</p><p>N</p><p>N</p><p>H</p><p>2</p><p>O</p><p>O</p><p>H</p><p>O</p><p>H</p><p>H</p><p>H</p><p>H</p><p>C</p><p>H</p><p>2</p><p>H</p><p>O</p><p>P</p><p>O</p><p>P</p><p>O</p><p>P</p><p>-</p><p>O</p><p>O</p><p>O</p><p>-</p><p>O</p><p>-</p><p>O</p><p>O</p><p>O</p><p>-</p><p>N</p><p>N</p><p>N</p><p>N</p><p>N</p><p>H</p><p>2</p><p>O</p><p>O</p><p>H</p><p>O</p><p>H</p><p>H</p><p>H</p><p>H</p><p>C</p><p>H</p><p>2</p><p>H</p><p>O</p><p>P</p><p>O</p><p>C</p><p>O</p><p>O</p><p>-</p><p>R</p><p>O</p><p>S</p><p>C</p><p>R</p><p>O</p><p>C</p><p>o</p><p>A</p><p>R</p><p>C</p><p>O</p><p>O</p><p>-</p><p>P</p><p>P</p><p>i</p><p>C</p><p>o</p><p>A</p><p>S</p><p>H</p><p>A</p><p>M</p><p>P</p><p>2</p><p>P</p><p>i</p><p>N</p><p>N</p><p>N</p><p>N</p><p>N</p><p>H</p><p>2</p><p>O</p><p>O</p><p>H</p><p>O</p><p>H</p><p>H</p><p>H</p><p>H</p><p>C</p><p>H</p><p>2</p><p>H</p><p>O</p><p>P</p><p>O</p><p>P</p><p>O</p><p>P</p><p>-</p><p>O</p><p>O</p><p>O</p><p>-</p><p>O</p><p>-</p><p>O</p><p>O</p><p>O</p><p>-</p><p>N</p><p>N</p><p>N</p><p>N</p><p>N</p><p>H</p><p>2</p><p>O</p><p>O</p><p>H</p><p>O</p><p>H</p><p>H</p><p>H</p><p>H</p><p>C</p><p>H</p><p>2</p><p>H</p><p>O</p><p>P</p><p>O</p><p>C</p><p>O</p><p>O</p><p>-</p><p>R</p><p>O</p><p>S</p><p>C</p><p>R</p><p>O</p><p>C</p><p>o</p><p>A</p><p>R</p><p>C</p><p>O</p><p>O</p><p>-</p><p>P</p><p>P</p><p>i</p><p>C</p><p>o</p><p>A</p><p>S</p><p>H</p><p>A</p><p>M</p><p>P</p><p>2</p><p>P</p><p>i</p> Fatty acid activation<p> EMBED ChemDraw.Document.4.5 </p><p>fatty acid</p><p>ATP</p><p>acyl-</p><p>adenylate</p><p>acyl-CoA</p>_1104392193.cdx</li><li><p>Summary of fatty aid activation:</p><p>fatty acid + ATP acyladenylate + PPi</p><p>PPi 2 Pi</p><p>acyladenylate + HS-CoA acyl-CoA + AMP</p><p>Overall: </p><p>fatty acid + ATP + HS-CoA acyl-CoA + AMP + 2 Pi</p></li><li><p>For most steps of the pathway there are multiple enzymes specific for particular fatty acid chain lengths. </p><p>b-Oxidation pathway:</p><p>Fatty acids are degraded in the mitochondrial matrix via the b-Oxidation Pathway. </p><p>Fatty acyl-CoA formed in cytosol by enzymes of outer mitochondrial membrane &amp; ER</p><p>inner </p><p>membrane </p><p>-Oxidation pathway in matrix</p><p>Mitochondrion</p></li><li><p>Fatty acyl-CoA formed outside can pass through the outer mitochondrial membrane (which has large VDAC channels), but cannot penetrate the inner membrane. </p><p>Many of the constituent enzymes are soluble proteins located in the mitochondrial matrix.</p><p>But enzymes specific for very long chain fatty acids are associated with the inner membrane, facing the matrix. </p><p>Fatty acyl-CoA formed in cytosol by enzymes of outer mitochondrial membrane &amp; ER</p><p>inner </p><p>membrane </p><p>-Oxidation pathway in matrix</p><p>Mitochondrion</p></li><li><p>Carnitine Palmitoyl Transferases catalyzes transfer of a fatty acid between the thiol of Coenzyme A and the hydroxyl on carnitine.</p><p>Transfer of the fatty acid moiety across the mitochondrial inner membrane involves carnitine.</p><p>H</p><p>3</p><p>C</p><p>N</p><p>C</p><p>H</p><p>2</p><p>C</p><p>H</p><p>C</p><p>H</p><p>2</p><p>C</p><p>H</p><p>3</p><p>C</p><p>H</p><p>3</p><p>O</p><p>H</p><p>C</p><p>O</p><p>O</p><p>-</p><p>+</p><p>R</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>+</p><p>H</p><p>3</p><p>C</p><p>N</p><p>C</p><p>H</p><p>2</p><p>C</p><p>H</p><p>C</p><p>H</p><p>2</p><p>C</p><p>H</p><p>3</p><p>C</p><p>H</p><p>3</p><p>O</p><p>C</p><p>O</p><p>O</p><p>-</p><p>+</p><p>C</p><p>R</p><p>O</p><p>+</p><p>H</p><p>S</p><p>C</p><p>o</p><p>A</p><p>H</p><p>3</p><p>C</p><p>N</p><p>C</p><p>H</p><p>2</p><p>C</p><p>H</p><p>C</p><p>H</p><p>2</p><p>C</p><p>H</p><p>3</p><p>C</p><p>H</p><p>3</p><p>O</p><p>H</p><p>C</p><p>O</p><p>O</p><p>-</p><p>+</p><p>R</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>+</p><p>H</p><p>3</p><p>C</p><p>N</p><p>C</p><p>H</p><p>2</p><p>C</p><p>H</p><p>C</p><p>H</p><p>2</p><p>C</p><p>H</p><p>3</p><p>C</p><p>H</p><p>3</p><p>O</p><p>C</p><p>O</p><p>O</p><p>-</p><p>+</p><p>C</p><p>R</p><p>O</p><p>+</p><p>H</p><p>S</p><p>C</p><p>o</p><p>A</p><p> EMBED ChemDraw.Document.4.5 </p><p>carnitine</p><p>fatty acyl carnitine</p><p>Carnitine Palmitoyl Transferase</p>_1008786327.cdx</li><li><p>Carnitine-mediated transfer of the fatty acyl moiety into the mitochondrial matrix is a 3-step process: </p><p>1. Carnitine Palmitoyl Transferase I, an enzyme on the cytosolic surface of the outer mitochondrial membrane, transfers a fatty acid from CoA to the OH on carnitine. </p><p>2. An antiporter in the inner mitochondrial membrane mediates exchange of carnitine for acylcarnitine. </p><p> cytosol mitochondrial matrix</p><p> O O</p><p> R-C-SCoA HO-carnitine HO-carnitine R-C-SCoA</p><p> HSCoA R-C-O-carnitine R-C-O-carnitine HSCoA</p><p> O O</p><p>1</p><p>2</p><p>3</p></li><li><p>3. Carnitine Palmitoyl Transferase II, an enzyme within the matrix, transfers the fatty acid from carnitine to CoA. (Carnitine exits the matrix in step 2.) </p><p>The fatty acid is now esterified to CoA in the matrix.</p><p> cytosol mitochondrial matrix</p><p> O O</p><p> R-C-SCoA HO-carnitine HO-carnitine R-C-SCoA</p><p> HSCoA R-C-O-carnitine R-C-O-carnitine HSCoA</p><p> O O</p><p>1</p><p>2</p><p>3</p></li><li><p>Control of fatty acid oxidation is exerted mainly at the step of fatty acid entry into mitochondria. </p><p>Malonyl-CoA (which is also a precursor for fatty acid synthesis) inhibits Carnitine Palmitoyl Transferase I. </p><p>Malonyl-CoA is produced from acetyl-CoA by the enzyme Acetyl-CoA Carboxylase. </p><p>H</p><p>3</p><p>C</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>C</p><p>H</p><p>2</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>-</p><p>O</p><p>O</p><p>C</p><p>H</p><p>3</p><p>C</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>C</p><p>H</p><p>2</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>-</p><p>O</p><p>O</p><p>C</p><p> EMBED ChemDraw.Document.4.5 </p><p>acetyl-CoA</p><p>malonyl-CoA</p>_1033147502.cdx</li><li><p>Activated Kinase, leading to decreased malonyl-CoA. </p><p>The decrease in malonyl-CoA concentration leads to increased activity of Carnitine Palmitoyl Transferase I. </p><p>Increased fatty acid oxidation then generates acetyl-CoA, for entry into Krebs cycle with associated ATP production.</p><p>AMP-Activated Kinase, a sensor of cellular energy levels, is allosterically activated by AMP, which is high in concentration when [ATP] is low.</p><p>Acetyl-CoA Carboxylase is inhibited when phosphorylated by AMP-</p><p>H</p><p>3</p><p>C</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>C</p><p>H</p><p>2</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>-</p><p>O</p><p>O</p><p>C</p><p>H</p><p>3</p><p>C</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>C</p><p>H</p><p>2</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>-</p><p>O</p><p>O</p><p>C</p><p> EMBED ChemDraw.Document.4.5 </p><p>acetyl-CoA</p><p>malonyl-CoA</p><p>ATP + HCO3</p><p> ADP + Pi</p><p>Acetyl-CoA Carboxylase</p><p>(inhibited by AMP-Activated Kinase)</p>_1155582881.cdx</li><li><p>AMP-Activated Kinase functions under a variety of conditions that lead to depletion of cellular ATP (reflected as increased AMP), including:</p><p>glucose deprivation, exercise, hypoxia &amp; ischaemia. </p><p>AMP-Activated Kinase regulates various metabolic pathways to:</p><p>promote catabolism leading to ATP synthesis <br />(e.g., stimulation of fatty acid oxidation)</p><p>inhibit energy-utilizing anabolic pathways <br />(e.g., fatty acid synthesis). </p><p>AMP-Activated Kinase in the hypothalamus of the brain is involved also in regulation of food intake.</p></li><li><p>bond between carbon atoms 2 &amp; 3. </p><p>There are different Acyl-CoA Dehydrogenases for short (4-6 C), medium (6-10 C),long and very long (12-18 C) chain fatty acids. </p><p>Very Long Chain Acyl-CoA Dehydrogenase is bound to the inner mitochondrial membrane. The others are soluble enzymes located in the mitochondrial matrix. </p><p>b-Oxidation Pathway: </p><p>Step 1. Acyl-CoA Dehydrogenase catalyzes oxidation of the fatty acid moiety of acyl-CoA to produce a double </p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>C</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>H</p><p>H</p><p>H</p><p>H</p><p>O</p><p>1</p><p>2</p><p>3</p><p>a</p><p>b</p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>C</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>H</p><p>H</p><p>O</p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>C</p><p>H</p><p>2</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>H</p><p>O</p><p>H</p><p>2</p><p>O</p><p>F</p><p>A</p><p>D</p><p>H</p><p>2</p><p>F</p><p>A</p><p>D</p><p>H</p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>C</p><p>H</p><p>2</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>O</p><p>H</p><p>+</p><p>+</p><p>N</p><p>A</p><p>D</p><p>H</p><p>N</p><p>A</p><p>D</p><p>+</p><p>C</p><p>H</p><p>3</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>+</p><p>O</p><p>H</p><p>S</p><p>C</p><p>o</p><p>A</p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>C</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>H</p><p>H</p><p>H</p><p>H</p><p>O</p><p>1</p><p>2</p><p>3</p><p>a</p><p>b</p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>C</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>H</p><p>H</p><p>O</p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>C</p><p>H</p><p>2</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>H</p><p>O</p><p>H</p><p>2</p><p>O</p><p>F</p><p>A</p><p>D</p><p>H</p><p>2</p><p>F</p><p>A</p><p>D</p><p>H</p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>C</p><p>H</p><p>2</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>O</p><p>H</p><p>+</p><p>+</p><p>N</p><p>A</p><p>D</p><p>H</p><p>N</p><p>A</p><p>D</p><p>+</p><p>C</p><p>H</p><p>3</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>+</p><p>O</p><p>H</p><p>S</p><p>C</p><p>o</p><p>A</p><p> EMBED ChemDraw.Document.4.5 </p><p>fatty acyl-CoA</p><p>trans-2-enoyl-CoA</p><p>fatty acyl-CoA acetyl-CoA</p><p>(2 C shorter)</p><p>Acyl-CoA Dehydrogenase</p>_1008570455.cdx_1008572580.cdx_1008574690.cdx_1008571291.cdx_1008570153.cdx</li><li><p>FAD is the prosthetic group that functions as e- acceptor for Acyl-CoA Dehydrogenase. Proposed mechanism: </p><p>A Glu side-chain carboxyl extracts a proton from the a-carbon of the substrate, facilitating transfer of 2 e- with H+ (a hydride) from the b position to FAD. </p><p>The reduced FAD accepts a 2nd H+, yielding FADH2.</p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>C</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>H</p><p>H</p><p>H</p><p>H</p><p>O</p><p>1</p><p>2</p><p>3</p><p>a</p><p>b</p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>C</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>H</p><p>H</p><p>O</p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>C</p><p>H</p><p>2</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>H</p><p>O</p><p>H</p><p>2</p><p>O</p><p>F</p><p>A</p><p>D</p><p>H</p><p>2</p><p>F</p><p>A</p><p>D</p><p>H</p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>C</p><p>H</p><p>2</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>O</p><p>H</p><p>+</p><p>+</p><p>N</p><p>A</p><p>D</p><p>H</p><p>N</p><p>A</p><p>D</p><p>+</p><p>C</p><p>H</p><p>3</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>+</p><p>O</p><p>H</p><p>S</p><p>C</p><p>o</p><p>A</p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>C</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>H</p><p>H</p><p>H</p><p>H</p><p>O</p><p>1</p><p>2</p><p>3</p><p>a</p><p>b</p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>C</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>H</p><p>H</p><p>O</p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>C</p><p>H</p><p>2</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>H</p><p>O</p><p>H</p><p>2</p><p>O</p><p>F</p><p>A</p><p>D</p><p>H</p><p>2</p><p>F</p><p>A</p><p>D</p><p>H</p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>C</p><p>H</p><p>2</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>O</p><p>H</p><p>+</p><p>+</p><p>N</p><p>A</p><p>D</p><p>H</p><p>N</p><p>A</p><p>D</p><p>+</p><p>C</p><p>H</p><p>3</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>O</p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>)</p><p>n</p><p>C</p><p>S</p><p>C</p><p>o</p><p>A</p><p>+</p><p>O</p><p>H</p><p>S</p><p>C</p><p>o</p><p>A</p><p> EMBED ChemDraw.Document.4.5 </p><p>fatty acyl-CoA</p><p>trans-2-enoyl-CoA</p><p>fatty acyl-CoA acetyl-CoA</p><p>(2 C shorter)</p><p>Acyl-CoA Dehydrogenase</p>_1008570455.cdx_1008572580.cdx_1008574690.cdx_1008571291.cdx_1008570153.cdx<p>H</p><p>3</p><p>N</p><p>+</p><p>C</p><p>C</p><p>O</p><p>O</p><p>-</p><p>C</p><p>H</p><p>2</p><p>C</p><p>H</p><p>2</p><p>C</p><p>H</p><p>O</p><p>-</p><p>O</p><p>H</p><p>3</p><p>N</p><p>+</p><p>C</p><p>C</p><p>O</p><p>O</p><p>-</p><p>C</p><p>H</p><p>2</p><p>C</p><p>H</p><p>2</p><p>C</p><p>H</p><p>O</p><p>-</p><p>O</p><p> EMBED ChemDraw.Document.6.0 </p><p>glutamate </p>_1126617240.unknown</li><li><p>The carbonyl O of the thioester substrate is hydrogen bonded to the 2'-OH of the ribityl moiety of FAD, giving this part of FAD a role in positioning the substrate and increasing acidity of the substrate a-proton. </p><p>H</p><p>3</p><p>C</p><p>(</p><p>C</p><p>H</p><p>2</p><p>