Nutr 470 1st Edition Lecture 16Current LectureThe TCA cycle provides substrates for the respiratory chain.The TCA cycle, also named as citric acid cycle andKrebs cycle, is the final common pathway for the oxidation of carbohydrate, lipid, and protein. In response to energy demands, the fatty acids of stored triglycerides are mobilized for use by peripheral tissues.The release of metabolic energy, in the form of fatty acids, is controlled by a complex series of interrelated cascades that result in the activation of hormone-sensitive lipase. Significance of Fatty Acid MetabolismFatty acids provide more than two times the amount of fuel as the same weight of carbohydrate and protein.Fatty acids are the main source of energy for the heart at all times.Whole bodyWhen liver and muscle glycogen is depleted, fatty acids become the main fuel for the entire body.BrainFatty acids are also used to make ketone bodies, a fuel for the brain when glycogen stores are depleted.Fatty Acid OxidationFatty acid oxidation, also known as beta oxidation, is the process by which fatty acids are broken into acetyl-CoA.These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.Place FAO occurs in mitochondrial matrix.Beta oxidation is termed because it occurs through the sequential removal of 2-carbon units by oxidationat the b-carbon position (next to carbonyl group) of the fatty acyl-CoA molecule. Sources of Free Fatty Acids Free fatty acidsHydrolysis of chylomicrons and VLDL – dietary and endogenous sources – mainly for storageHydrolysis of triglycerides – adipose tissueUnder fasting conditions, free fatty acids, also known as non-esterified fatty acids (NEFA), are derived mainly from the hydrolysis of triglycerides by hormone-sensitive lipase (HSL) in fat cells.Reactions of Fatty Acid OxidationFFA must be activated in the cytosol before being oxidized in the mitochondria.Activation is catalyzed by fatty acyl-CoA ligase Transferring acyl-CoA into mitochondria is the rate-determining step of beta oxidation. <<— ImportantCarnitine palmitoyltransferase 1 CPT1, present in the out mitochondrial membrance, converts long chainacyl-CoA to acylcarnitine.Inside mitochondrial matrix, CPT2 converts acylcarnitine back to acyl-CoA.Modulating CPT1 activities controls the rate of b-oxidation. Reaction of Fatty Acid OxidationThe β-oxidation of fatty acids occurs via four recurring steps1) Oxidation by FADThe formation of a double bond between the C-2 and C-3 is catalyzed by acyl-CoA dehydrogenase – generation of enoyl-CoA. 2) HydrationThe hydration of the bond between C-2 and C-3 is catalyzed by enoyl CoA hydratase – generation of hydroxyacyl-CoA.3)Oxidation by NAD+Hydroxyacyl-CoA dehydrogenase converts the hydroxyl group into a keto group – generation of 3-ketoacyl-CoA.4) Thiolysis3-ketoacyl-CoA is split at the 2,3-position by thiolase to generate acyl-CoA and acetyl-CoA.Regulations of Fatty Acid OxidationTransferring acyl-CoA into mitochondria is the rate-determining step of beta oxidation.Carnitine palmitoyltransferase 1CPT1 is inhibited by malonyl-CoA, an intermediate of fatty acid synthesisGlucose and insulin work together to increase the levels of malonyl-CoA, which in turn suppresses fatty acid oxidation. Fatty Acid Oxidation and Energy ExpenditureEnergy expenditure can be quantified using indirect calorimetry.Fatty acid oxidation makes a greater contribution to energy expenditure than glucose oxidation.Fatty acid oxidation in muscle makes a predominant contribution to whole body energy expenditure.Fatty Acid Oxidation in Obesity and DiabetesImpairment in fatty acid oxidation is associated with insulin resistance and hyperglycemia.Obesity and insulin resistanceFat accumulation is due to the rates of fatty acid synthesis larger than those of fatty acid oxidation.Fat storage in adipose tissue contributes to insulin resistance.SummarySources of fatty acidsSignificance of beta oxidationReaction & regulation of beta oxidationFatty acids and energy