Generation and Storage of Energy The oxidation of fatty acids (FA)in triacylglycerols is the _________________________________ for most organisms Their carbon chains are in a highly reduced form The energy yield per gram of fatty acid oxidized is greater than that per gram of carbohydrate oxidized

Catabolism of Lipids ____________ catalyze hydrolysis of bonds between fatty acid and the rest of triacylglycerols __________________ catalyze hydrolysis of bonds between fatty acid and the rest of phosphoacylglycerols May have multiple sites of action

Fatty Acid Activation Fatty acid oxidation begins with ____________ A thioester bond is formed between the carboxyl group of the FA and the thiol of CoA-SH

The Role of Carnitine in Acyl-CoA Transfer The acyl-CoA crosses the ____________ mitochondrial membrane, but not the ____________ membrane The acyl group is then transferred to carnitine, carried across the inner mitochondrial membrane, and transferred to mitochondrial CoA-SH Carnitine Palmitoyltransferase (CPT-1) has specificity for acyl groups between 14 and 18 carbons long

The Role of Carnitine in Acyl-CoA Transfer

-Oxidation -Oxidation: a series of reactions that cleaves carbon atoms __________ at a time from the carboxyl end of a fatty acid The complete cycle of one -oxidation requires four enzymes Reaction 1: Oxidation of the , carbon-carbon single bond to a carbon-carbon double bond Reaction 2: Hydration of the carbon-carbon double bond Reaction 3: Oxidation of the -hydroxyl group to a carbonyl group Reaction 4: Cleavage of the carbon chain by a reverse Claisen reaction

-Oxidation

Summary Fatty acids are activated and transported to the mitochondrial matrix for further catabolism The breakdown of fatty acids takes place in the mitochondrial matrix and proceeds by successive removal of two-carbon units as acetyl-CoA Each cleavage of a two-carbon moiety requires a four-step reaction sequences called -oxidation

Energy Yield from FA Oxidation The energy released by the oxidation of acetyl-CoA formed by -oxidation of FA can drive ___ synthesis ____________ cycles of -oxidation are required for the oxidation of stearic acid to acetyl-CoA

Energy Yield from FA Oxidation The overall equation for oxidation of stearic acid can be obtained by adding the equations for b-oxidation, the ______________________, and ___________________________________

Energy Yield from FA Oxidation

Summary The complete oxidation of FA by the citric acid cycle and the electron transport chain releases large amounts of energy When we include the reoxidation of NADH and FADH2 from -oxidation and the citric acid cycle, we obtain a net yield of 120 ATP for a single molecule of stearic acid

Catabolism of Odd-Numbered FA Odd-numbered FA are not frequently encountered, but do also undergo -oxidation The last -oxidation cycle of a fatty acid with an odd number of carbons gives _______________ _______________

Oxidation of an Unsaturated FA A cis-trans isomerization is needed to convert unsaturated FA to acetyl-CoA This enzyme is known as an ______________ Oxidation of unsaturated FA does not generate as much ATP relative to saturated FA with the same # of carbons

Oxidation of an Unsaturated FA

Summary FA with odd number of carbons produce propionyl-CoA in the last step of the oxidation Propionyl-CoA can be converted to succinyl- CoA, which plays a role in the citric acid cycle The oxidation of unsaturated FA requires enzymes that catalyze isomerization around the double bonds so that oxidation can proceed

Ketone Bodies Formation of ketone bodies occurs when the amount of acetyl-CoA produced is excessive compared to the amount of oxaloacetate available to react with it Intake high in _______ and low in ______________ Diabetes not suitably controlled Starvation Ketone bodies are: acetone, -hydroxybutyrate, and acetoacetate Formed principally in ___________ mitochondria Can be used as a fuel in most tissues and organs

Ketone Bodies Summary: • If an organism has an excess of acetyl-CoA, it produces ketone bodies. • This situation can arise from an excessive intake of fats compared to carbohydrates, or from diabetes.

Fatty Acid Biosynthesis Biosynthesis is not exact reversal of oxidation Biosynthetic reactions occur in the ___________

Fatty Acid Biosynthesis Carboxylation of acetyl-CoA occurs in the cytosol Catalyzed by acetyl-CoA carboxylase ___________ is the carrier of the carboxyl group Malonyl-CoA is key intermediate that is produced

Biosynthesis of Palmitate

Sites of Fatty Acid Metabolism in an Animal Cell

Comparison of FA Degradation and Biosynthesis Summary • Acetyl-CoA is transported to the cytosol and converted to malonyl-CoA • The biosynthesis of FA proceeds by the addition of 2-carbon units to the hydrocarbon chain. • The process is catalyzed by the fatty-acid synthase complex Comparison of FA Degradation and Biosynthesis

Triacylglycerol Biosynthesis Lipids such as triacylglycerols, phosphoacylglycerols, and steroids are derived ___________ __________________

Biosynthesis of Phosphoacylglycerols

Biosynthesis of Sphingosine/Ceramide Requires starting materials _______________ and serine

Cholesterol Biosynthesis All carbon atoms of cholesterol and steroids synthesized from it are derived from the two-carbon acetyl group of ___________________ Involves many reaction steps Involvement of ___________ units are key to the biosynthesis of steroids and other biomolecules known as ________

Overall View of Cholesterol Biosynthesis

Cholesterol Biosynthesis Synthesis begins with the condensation of 2 molecules of __________________ Next, condensation with a 3RD molecule of __________ The formation of mevalonate is completed by reduction of the thioester to a 1° alcohol

Mevalonate to Squalene The pyrophosphosphorylation of the 1° alcohol of mevalonate (two moles of ATP) is followed by phosphorylation of the 3° alcohol (one mole of ATP), then the concerted decarboxylation and -elimination of phosphate ion gives ______________________ ______________________ Then there is an enzyme-catalyzed isomerization of the carbon-carbon double bond that gives dimethylallyl pyrophosphate Dimethylallyl pyrophosphate is then converted to isopentyl pyrophosphate, which is followed by H+ loss to give farnesyl pyrophosphate The joining together of two units of farnesyl pyrophosphate (C15) units by a 2-electron oxidation gives ___________ (C30)

The Conversion of Mevalonate to Squalene

Squalene to Cholesterol

Cholesterol as a Precursor Cholesterol is the precursor for a number of ______________________ ______________________

Role of Cholesterol in Heart Disease Lipids are transported in the blood stream by ______________________ Cholesterol and its fatty acid esters are packaged into several classes of lipoproteins for transport

The LDL Particle

The Fate of Cholesterol

Summary The biosynthesis of cholesterol proceeds by the condensation of five-carbon isoprenoid units Isoprenoid units in turn are derived from the reaction of three acetyl-CoA units Once cholesterol is formed, it serves as a precursor for other steroids Cholesterol must be packaged for transport in the bloodstream. Some of these forms of cholesterol play a role in heart disease