Chapter 24 fatty acid catabolism

Chapter 24 Fatty Acid Catabolism Outline • 24.1 Mobilization of Fats from Dietary Intake and Adipose Tissue • 24.2 Beta-Oxidation of Fatty Acids • 24.3 Odd-Carbon Fatty Acids • 24.4 Unsaturated Fatty Acids • 24.5 Other Aspects of Fatty Acid Oxidation • 24.6 Ketone Bodies Why Fatty Acids? (For energy storage?) • Two reasons: – The carbon in fatty acids (mostly CH2) is almost completely reduced (so its oxidation yields the most energy possible) – Fatty acids are not hydrated (as monoand polysaccharides are), so they can pack more closely in storage tissues Fat from Diet & Adipose Cells Triacylglycerols either way • Triglycerides represent the major energy input in the modern American diet (but it wasn't always this way) • Triglycerides are also the major form of stored energy in the body • See Table 24.1 • Hormones (glucagon, epinephrine, ACTH) trigger the release of fatty acids from adipose tissue Figure 24.1 · Scanning electron micrograph of an adipose cell (fat cell) Globules of triacylglycerols occupy most of the volume of such cells Figure 24.2 · Liberation of fatty acids from triacylglycerols in adipose tissue is hormonedependent Figure 24.3 · (a) A duct at the junction of the pancreas and duodenum secretes pancreatic juice into the duodenum, the first portion of the small intestine (b) Hydrolysis of triacylglycerols by pancreatic and intestinal lipases Pancreatic lipases cleave fatty acids at the C-1 and C-3 positions Resulting monoacylglycerols with fatty acids at C-2 are hydrolyzed by intestinal lipases Fatty acids and monoacylglycerols are absorbed through the intestinal wall and assembled into lipoprotein aggregates termed chylomicrons • Figure 24.4 · In the small intestine, fatty acids combine with bile salts in mixed micelles, which deliver fatty acids to epithelial cells that cover the intestinal villi • Triacylglycerols are formed within the epithelial cells Beta Oxidation of Fatty Acids Knoop showed that fatty acids must be degraded by removal of 2-C units • Albert Lehninger showed that this occurred in the mitochondria • F Lynen and E Reichart showed that the 2C unit released is acetyl-CoA, not free acetate • The process begins with oxidation of the carbon that is "beta" to the carboxyl carbon, so the process is called"beta-oxidation" Figure 24.5 The oxidative breakdown of phenyl fatty acids observed by Franz Knoop • He observed that fatty acid analogs with even numbers of carbon atoms yielded phenyl acetate, whereas compounds with odd numbers of carbon atoms produced only benzoate Unsaturated Fatty Acids Consider monounsaturated fatty acids: • Oleic acid, palmitoleic acid • Normal b-oxidation for three cycles • cis-3 acyl-CoA cannot be utilized by acyl-CoA dehydrogenase • Enoyl-CoA isomerase converts this to trans- 2 acyl CoA  b-oxidation continues from this point Polyunsaturated Fatty Acids Slightly more complicated • Same as for oleic acid, but only up to a point: – cycles of b-oxidation – enoyl-CoA isomerase – more round of b-oxidation – trans- 2, cis- 4 structure is a problem! • 2,4-Dienoyl-CoA reductase to the rescue! Peroxisomal b-Oxidation Peroxisomes - organelles that carry out flavin-dependent oxidations, regenerating oxidized flavins by reaction with O2 to produce H2O2 • Similar to mitochondrial b-oxidation, but initial double bond formation is by acyl-CoA oxidase • Electrons go to O2 rather than e- transport • Fewer ATPs result Branched-Chain Fatty Acids An alternative to b-oxidation is required • Branched chain FAs with branches at odd-number carbons are not good substrates for b-oxidation  -oxidation is an alternative • Phytanic acid -oxidase decarboxylates with oxidation at the alpha position  b-oxidation occurs past the branch Ketone Bodies • • • • • • A special source of fuel and energy for certain tissues Some of the acetyl-CoA produced by fatty acid oxidation in liver mitochondria is converted to acetone, acetoacetate and bhydroxybutyrate These are called "ketone bodies" Source of fuel for brain, heart and muscle Major energy source for brain during starvation Synthesis in Figure 24.28 They are transportable forms of fatty acids! Ketone Bodies - II Interesting Aspects of Their Synthesis • Occurs only in the mitochondrial matrix • First step - Figure 24.28 - is reverse thiolase • Second reaction makes HMG-CoA • These reactions are mitochondrial analogues of the (cytosolic) first two steps of cholesterol synthesis • Third step - HMG-CoA lyase - is similar to the reverse of citrate synthase Ketone Bodies and Diabetes "Starvation of cells in the midst of plenty" • Glucose is abundant in blood, but uptake by cells in muscle, liver, and adipose cells is low • Cells, metabolically starved, turn to gluconeogenesis and fat/protein catabolism • In type I diabetics, OAA is low, due to excess gluconeogenesis, so Ac-CoA from fat/protein catabolism does not go to TCA, but rather to ketone body production • Acetone can be detected on breath of type I diabetics ... • 24. 1 Mobilization of Fats from Dietary Intake and Adipose Tissue • 24. 2 Beta-Oxidation of Fatty Acids • 24. 3 Odd-Carbon Fatty Acids • 24. 4 Unsaturated Fatty Acids • 24. 5 Other Aspects of Fatty. .. Fatty Acids • 24. 5 Other Aspects of Fatty Acid Oxidation • 24. 6 Ketone Bodies Why Fatty Acids? (For energy storage?) • Two reasons: – The carbon in fatty acids (mostly CH2) is almost completely... lipases Pancreatic lipases cleave fatty acids at the C-1 and C-3 positions Resulting monoacylglycerols with fatty acids at C-2 are hydrolyzed by intestinal lipases Fatty acids and monoacylglycerols