Fatty Acid Metabolism

Fatty Acid MetabolismWhy are fatty acids important to cells?fuel moleculesstored as triacylglycerolsbuilding blocksphospholipidsglycolipidsprecursors of hormones and other messengersused to target proteins to membrane sites

Fatty Acid MetabolismWhy do triacylglycerols store large amounts of energy?fatty acid portion is highly reducednonpolar molecules are stored in anhydrous formWhere are triacylglycerols stored?adipocytes

Fatty Acid MetabolismWhat is needed for triacylglycerol breakdown?bile saltsmade in liver, stored in gall bladderglycocholatelipasespancreashydrolyze ester bond

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

Fatty Acid MetabolismWhat are chylomicrons?particles consisting of triacylglycerols and proteinapolipoproteins

Fatty Acid MetabolismHow are fatty acids made available to peripheral tissues as an energy source?hormones trigger lipolysis in adipose tissueepinephrine, glucagon, ACTHinsulin inhibits lipolysisreleased fatty acids insoluble in plasmamust be attached to serum albumin for transport

Fatty Acid Metabolism

Fatty Acid MetabolismWhat happens to the glycerol released?converted to glyceraldehyde-3-PO4glycolysisgluconeogenesis

Fatty Acid DegradationWhat must happen to fatty acids for them to be oxidized?activatedtransported into mitocondria

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

Fatty Acid DegradationWhat is the reaction sequence for the oxidation of fatty acids?first step is an oxidationacyl CoA dehydrogenase

Fatty Acid DegradationSecond step is a hydrationenoyl CoA hydratasestereospecificonly L isomer is formed

Fatty Acid DegradationThird step is a second oxidationL-3-hydroxyacyl CoA dehydrogenase

Fatty Acid DegradationLast step is cleavage of 3-ketoacyl CoA by thiol group of CoAacyl CoA shortened by 2 carbonsacetyl CoA formed

Fatty Acid DegradationWhat are the products of fatty acid degradation?For a C16 fatty acid8 acetyl CoA7 FADH27NADH + 7 H+How much energy does this generate?7 x 1.5 ATP = 10.57 x 2.5 ATP = 17.5 8 x 10 ATP = 80Total = 108 ATP 2 ATP (activation) = 106 ATP

Fatty Acid DegradationUnsaturated fatty acids require additional steps for degradationisomerizationshifts position and configuration of a double bondreductionneeded to remove double bond in wrong position

Fatty Acid Degradation

Fatty Acid DegradationHow is the oxidation of odd-chain fatty acids different from even-chain ones?in final round of degradation products are acetyl CoA and proprionyl CoAproprionyl CoA is converted to succinyl CoA

Fatty Acid DegradationProprionyl CoA is carboxylated to give D-methylmalonyl CoAcatalyzed by proprionyl CoA carboxylaseuses biotin

Fatty Acid DegradationD-methylmalonyl CoA is racemized to L formmethylmalonyl CoA mutaseuses a derivative of vitamin B12

Fatty Acid DegradationIn last step a 5-deoxyadenosyl free radical removes a H atom to aid in rearrangement of L-methylmalonyl CoA to succinyl CoA

Fatty Acid DegradationWhere, in addition to the mitocondria does fatty acid oxidation take place?peroxisomesHow is this different from oxidation?in first step electrons are transferred to O2

Fatty Acid DegradationWhat are ketone bodies and under what conditions are they formed?acetoacetate, -hydroxybutyrate, acetonewhen fats are rapidly broken down

Fatty Acid DegradationHow can ketone bodies be used?major fuel source for heart muscle and kidney cortexduring starvation or diabetes may be used by brainhigh levels of acetoacetate decreases lipolysis

What is one important difference between plants and animals with respect to fatty acid metabolism?animals cannot use fatty acids to make glucosespecifically, in animals acetyl CoA cannot be converted to oxaloacetateplants have enzymes associated with glyoxylate cycle that allow acetyl CoA to form oxaloacetateFatty Acid Degradation

Fatty Acid MetabolismWhat are some of the differences between fatty acid degradation and synthesis?location in celluse of acyl carrier protein vs. coenzyme Aassociation of synthetic enzymes into complexuse of NADPH as opposed to NAD+ and FAD

Fatty Acid SynthesisWhat is the first committed step in fatty acid synthesis?formation of malonyl CoAacetyl CoA carboxylase - biotin

Fatty Acid SynthesisIntermediates in fatty acid synthesis are linked to an acyl carrier proteinrole similar to coenzyme A

Fatty Acid SynthesisWhat are the steps in fatty acid synthesis catalyzed by the fatty acid synthase complex?

Fatty Acid Synthesis

Fatty Acid Synthesis

Fatty Acid Synthesis

Fatty Acid Synthesis

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

Fatty Acid SynthesisSince synthesis occurs in cytosol acetyl CoA must be transported from mitocondriacarried by citratecleavage of citrate requires an ATP

Fatty Acid SynthesisFrom where does NADPH needed for synthesis come?pentose phosphate pathway6 molecules reduction of OAA to malate followed by oxidative decarboxylation of malate to pyruvate8 molecules

Fatty Acid MetabolismWhich enzyme plays a key role in regulating fatty acid metabolism?acetyl CoA carboxylaseGlobal control of ACC by glucagon, epinephrine and insulininsulin activatesglucagon and epinephrine inactivate

Fatty Acid MetabolismACC is inhibited by phosphorylation and allosterically activated by binding of citrate

Synthesis and degradation are reciprocally regulatedstarvation degradation occurs because epinephrine & glucagon stimulate lipolysisfed state insulin inhibits lipolysisACC also influences degradationmalonyl CoA inhibits carnitine acetyltransferaselimits beta oxidation in mitocondriaLong-term control mediated by sythesis and degradation of key enzymesadaptive controlFatty Acid Metabolism