3/9/151Biochemistry401Lecture 26Fatty Acids: Overview TriacylglycerolsCatabolism of TriacylglycerolDietary SourcesEndogenousFatty Acid Oxidation Catabolism of Saturated Fatty Acids Catabolism of Unsaturated Fatty Acids Carboxylate Hydrocarbon Chain 18C Monounsaturated Fatty Acid 16C Saturated Fatty Acid At physiologic pH, carboxylic acid is deprotonated to carboxylate Double bonds kink the hydrocarbon chain Fatty Acids Overview Fatty acids are hydrocarbon chains that end in carboxylic acid Three stearates C18 One oleate between two stearates Fatty acids can have short medium or long hydrocarbon chains They can also have differing degrees of saturation Long saturated fatty acids pack well, and so have higher melting temperatures than shorter or than unsaturated fatty acids.3/9/152C16:0 C18:1 (cis-Δ9) Monounsaturated Fatty Acid Saturated Fatty Acid 2 1 3 4 5 6 7 8 9 Two means of identifying locations of double bonds 1) Numbering from the Carboxylate End: identify the double bond location by the number of the carbon in the double bond closer to the carboxylate end 2) Numbering from the methyl end, called the ω (omega) end: the carbon in the double bond that is closer to the ω end identifies the location of the double bond. CIn animals even number: 16-24 carbons, unbranched. Most common are 16 and 18 carbon FAs. Double bonds are cis, not trans. Polyunsaturated double bonds are separated by a methylene group. Odd- & branched-chain fatty acids are synthesized by bacteria. Oddly enough, ruminant animal fat contains odd numbered fatty acids.3/9/153Odd-numbered and branched chain fatty acids are found in bacteria.They are rare in animals!! Bacteria found in the digestive tract of ruminant animals are ingested by these animals, and branched chain fatty acids are found in the body fat of these animals. !Odd-numbered and Branched Chain Fatty Acids TriacylglycerolDiacylglycerol + 1 FAMonoacylglycerol + 2 FAGlycerol !Three fatty acids!Covalent ester linkage!TriacylglycerolGlycerol + 3 FATriacylglycerols (fats) High energy fuel. Preferred Fuel of: • Liver • Heart Used as fuel by skeletal muscles. Most of our stored fuel is triacylglycerol. Yields a greater quantity of ATP per gram than Glycogen: • Highly reduced hydrocarbon FAs • Hydrophobic - no hydration shell Nucleus Fats Adipocyte Glycerol !Three fatty acids!Covalent ester linkage!3/9/154Bile Salts, amphipathic derivatives of cholesterol • Synthesized in the liver • Stored in the gall bladder • Released into the small intestine • Emulsify TAGs. Catabolism of dietary fats begins in the small intestine a bile salt blood adipocytes, and muscle Glucagon, Epinephrine Induce Lipolysis Through Activation of PKA3/9/155mitochondria Nucleus Fats Triacylglycerols (fats) High energy fuel. Preferred Fuel of: • Liver • Heart Used as fuel by skeletal muscles. Most of our stored fuel is triacylglycerol. Yields a greater quantity of ATP per gram than Glycogen: • Highly reduced hydrocarbon FAs • Hydrophobic - no hydration shell Adipocyte Bile Salts, amphipathic derivatives of cholesterol • Synthesized in the liver, • Stored in the gall bladder • Released into the small intestine • Emulsify TAGs. Catabolism of dietary fats begins in the small intestine , a bile salt3/9/156TAGs cannot diffuse through cell membranes. FAs are removed through hydrolysis by pancreatic lipase. FAs and Monoacylglycerol can enter intestinal mucosal cells. blood adipocytes, and muscle Glucagon, Epinephrine Induce Lipolysis Through Activation of PKA3/9/157mitochondria Glycerol Can Be Used by the Liver to Synthesize Glyceraldehyde 3-P for Use in Glycolysis, or Gluconeogenesis. Oxidation Triose Phosphate Isomerase Oxidation of fatty acids occurs in mitochondria Begins with activation of the fatty acid by CoA.3/9/158Two step process occurs on the outer mitochondrial membrane 1) Activation: The fatty acid activated by ATP to form acyl adenylate and PPi is released. The reaction is driven forward through hydrolysis of PPi, and is irreversible. 2) Transfer: fatty acid is transferred to CoA and AMP is released. Fatty Acid Oxidation Occurs in the Mitochondrial Matrix The activated fatty acid is transferred to carnitine for transport across the inner mitochondrial membrane to the matrix. Enzyme: Carnitine acyltransferase I Once in the mitochondrial matrix, CoA is again attached and carnitine is released. Enzyme: Carnitine acyltransferase II Long-chain fatty acids (greater than 8-10C)must be transported across the inner mitochondrial membrane3/9/159Because the beta carbon will be oxidized, fatty acid degradation is also called the beta-oxidation of fatty acids 1) Oxidation I 2) Hydration 3) Oxidation II 4) Thiolysis, removal of an activated two carbon acetyl unit through addition of Coenzyme A Oxidation of activated saturated fatty acids occurs in the mitochondria in 4 steps: First FAD Next NAD+ Oxidation reductions require Electron carriers:3/9/15103/9/1511Round 1 Round 2 Round 3 With each round of β-oxidation, one Acetyl CoA is produced Hydration Double bonds present a problem, and require a special enzyme: cis-∆3 -Enoyl CoA Isomerase Causes a rearrangement that creates a double bond at C-2 in an isomerization reaction yielding trans-∆2 -Enoyl CoA Can enter β-oxidation pathway Saturated Oxidation 1 Hydration Oxidation 2 With monounsaturated fatty acids, Oxidation 1 and its FADH are lost Thiolysis3/9/1512Polyunsaturated Fatty Acids present special problems due to its complexity…we will not be covering this topic… How many cycles are needed to break palmitate down completely to Acetyl CoA? How many Acetyl CoA produced? How many NADH and how many FADH2 produced? 16C Saturated Fatty Acid3/9/151316C Saturated Fatty Acid How many cycles are needed to break palmitate down completely to Acetyl CoA?_________________ How many Acetyl CoA produced? ___________ How many NADH and how many FADH2 produced? _______________________ This is the end of Lecture 26…!have a great
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