Fatty Acid Metabolism Fatty Acid Metabolism n Why

Fatty Acid Metabolism

Fatty Acid Metabolism n Why are fatty acids important to cells? n fuel molecules n n stored as triacylglycerols building blocks phospholipids n glycolipids n n n precursors of hormones and other messengers used to target proteins to membrane sites

Fatty Acid Metabolism n Why do triacylglycerols store large amounts of energy? n n n fatty acid portion is highly reduced nonpolar molecules are stored in anhydrous form Where are triacylglycerols stored? n adipocytes

Fatty Acid Metabolism n What is needed for triacylglycerol breakdown? n bile salts made in liver, stored in gall bladder n glycocholate n n lipases pancreas n hydrolyze ester bond n

Fatty Acid Metabolism n What are triacylglycerols broken down into? Fatty acids and monoacylglcerols are absorbed across plasma membrane of intestinal epithelial cells.

Fatty Acid Metabolism n What are chylomicrons? n particles consisting of triacylglycerols and protein n apolipoproteins

Fatty Acid Metabolism n How are fatty acids made available to peripheral tissues as an energy source? n hormones trigger lipolysis in adipose tissue epinephrine, glucagon, ACTH n insulin inhibits lipolysis n n released fatty acids insoluble in plasma n must be attached to serum albumin for transport

Fatty Acid Metabolism

Fatty Acid Metabolism n What happens to the glycerol released? n converted to glyceraldehyde-3 -PO 4 n n glycolysis gluconeogenesis

Fatty Acid Degradation n What must happen to fatty acids for them to be oxidized? n n activated transported into mitocondria

Fatty Acid Degradation n What is the role of carnitine in fatty acid oxidation? n transport into mitocondria matrix

Fatty Acid Degradation n What is the reaction sequence for the oxidation of fatty acids? n first step is an oxidation n acyl Co. A dehydrogenase

Fatty Acid Degradation n Second step is a hydration n n enoyl Co. A hydratase stereospecific n only L isomer is formed

Fatty Acid Degradation n Third step is a second oxidation n L-3 -hydroxyacyl Co. A dehydrogenase

Fatty Acid Degradation n Last step is cleavage of 3 -ketoacyl Co. A by thiol group of Co. A n n acyl Co. A shortened by 2 carbons acetyl Co. A formed

Fatty Acid Degradation n What are the products of fatty acid degradation? n For a C 16 fatty acid n n 8 acetyl Co. A 7 FADH 2 7 NADH + 7 H+ How much energy does this generate? n n 7 x 1. 5 ATP = 10. 5 7 x 2. 5 ATP = 17. 5 8 x 10 ATP = 80 Total = 108 ATP – 2 ATP (activation) = 106 ATP

Fatty Acid Degradation n Unsaturated fatty acids require additional steps for degradation n isomerization n n shifts position and configuration of a double bond reduction n needed to remove double bond in wrong position

Fatty Acid Degradation

Fatty Acid Degradation n How is the oxidation of odd-chain fatty acids different from even-chain ones? n n in final round of degradation products are acetyl Co. A and proprionyl Co. A is converted to succinyl Co. A

Fatty Acid Degradation n Proprionyl Co. A is carboxylated to give Dmethylmalonyl Co. A n catalyzed by proprionyl Co. A carboxylase n uses biotin

Fatty Acid Degradation n D-methylmalonyl Co. A is racemized to L form n methylmalonyl Co. A mutase n uses a derivative of vitamin B 12

Fatty Acid Degradation n In last step a 5 -deoxyadenosyl free radical removes a H atom to aid in rearrangement of Lmethylmalonyl Co. A to succinyl Co. A

Fatty Acid Degradation n Where, in addition to the mitocondria does fatty acid oxidation take place? n n peroxisomes How is this different from oxidation? n in first step electrons are transferred to O 2

Fatty Acid Degradation n What are ketone bodies and under what conditions are they formed? n n acetoacetate, -hydroxybutyrate, acetone when fats are rapidly broken down

Fatty Acid Degradation n How can ketone bodies be used? n n n major fuel source for heart muscle and kidney cortex during starvation or diabetes may be used by brain high levels of acetoacetate decreases lipolysis

Fatty Acid Degradation n What is one important difference between plants and animals with respect to fatty acid metabolism? n n n animals cannot use fatty acids to make glucose specifically, in animals acetyl Co. A cannot be converted to oxaloacetate plants have enzymes associated with glyoxylate cycle that allow acetyl Co. A to form oxaloacetate

Fatty Acid Metabolism n What are some of the differences between fatty acid degradation and synthesis? n n location in cell use of acyl carrier protein vs. coenzyme A association of synthetic enzymes into complex use of NADPH as opposed to NAD+ and FAD

Fatty Acid Synthesis n What is the first committed step in fatty acid synthesis? n formation of malonyl Co. A n acetyl Co. A carboxylase - biotin

Fatty Acid Synthesis n Intermediates in fatty acid synthesis are linked to an acyl carrier protein n role similar to coenzyme A

Fatty Acid Synthesis n What are the steps in fatty acid synthesis catalyzed by the fatty acid synthase complex?

Fatty Acid Synthesis

Fatty Acid Synthesis n Mammalian FAS is a homodimer with each chain containing three domains joined by flexible regions.

Fatty Acid Synthesis n Since synthesis occurs in cytosol acetyl Co. A must be transported from mitocondria n n carried by citrate cleavage of citrate requires an ATP

Fatty Acid Synthesis n From where does NADPH needed for synthesis come? n pentose phosphate pathway n n 6 molecules reduction of OAA to malate followed by oxidative decarboxylation of malate to pyruvate n 8 molecules

Fatty Acid Metabolism n Which enzyme plays a key role in regulating fatty acid metabolism? n n acetyl Co. A carboxylase Global control of ACC by glucagon, epinephrine and insulin n n insulin activates glucagon and epinephrine inactivate

Fatty Acid Metabolism n ACC is inhibited by phosphorylation and allosterically activated by binding of citrate

Fatty Acid Metabolism n Synthesis and degradation are reciprocally regulated n n n starvation – degradation occurs because epinephrine & glucagon stimulate lipolysis fed state – insulin inhibits lipolysis ACC also influences degradation n malonyl Co. A inhibits carnitine acetyltransferase n n limits beta oxidation in mitocondria Long-term control mediated by sythesis and degradation of key enzymes n adaptive control