Fatty Acid Catabolism and Digestion

Fatty Acid Catabolism

• Fats are esters of glycerol and fatty acids.
• Highly reduced structures, similar to hydrocarbons, providing high energy.
• Liver and heart use fats for ~80% of energy.
• Fats are hydrophobic and inert, storing easily in lipid droplets without raising cell osmolarity.
• Fats are a sole energy source for hibernating animals and migratory birds.

Digestion, Mobilization, and Transport of Fats

• Bile salts emulsify dietary fats in the small intestine, forming mixed micelles.
• Intestinal lipases degrade triacylglycerols.
• Fatty acids and other breakdown products are absorbed by the intestinal mucosa and converted into triacylglycerols.
• Triacylglycerols are incorporated with cholesterol and apolipoproteins into chylomicrons.
• Chylomicrons travel through the lymphatic and bloodstream to tissues.
• Lipoprotein lipase converts triacylglycerols into fatty acids and glycerol.

Structure of Chylomicrons

• Size: 100-500 nm.
• Composition: triacylglycerols (80%), phospholipids, cholesterol, cholesterol esters, and apolipoproteins (lipid-binding proteins).
• Different combinations of lipids and proteins: chylomicrons, VLDL, and VHDL.
• Apolipoproteins are recognized by cell surface receptors.

Mobilization of Triacylglycerols Stored in Adipose Tissue

• Binding of epinephrine to adipocyte receptors stimulates adenylyl cyclase.
• cAMP activates PKA.
• PKA phosphorylates perilipin, making fats accessible to hormone-sensitive lipase (HSL).
• HSL hydrolyzes triglycerides into fatty acids and glycerol.
• Fatty acids leave adipocytes and are transported by serum albumin to muscles.

Metabolism of Glycerol

• Glycerol accounts for ~5% of total fat energy.
• Glycerol is converted into glyceraldehyde 3-phosphate and enters glycolysis.
• Phosphorylated species are trapped in the cytoplasm.

Fatty Acid "Activation"

• Enzymes for fatty acid oxidation are in the mitochondrial matrix.
• Fatty acids are conjugated with CoA in the cytoplasm before entering the mitochondria.
• Conjugation is highly exothermic due to pyrophosphate release, which is further hydrolyzed into phosphates.

Fatty Acid Transport into Mitochondria

• Carnitine acts as a fatty acid shuttle between the cytosol and the inner mitochondrial membrane.
• Fatty acids are converted into carnitine esters.

Oxidation of Fatty Acids

• In humans, beta-oxidation occurs primarily in the mitochondria.
• Stages involve sequential beta-oxidation rounds to generate acetyl-CoA, oxidation of acetyl-CoA to CO2, FADH2, and NADH using the citric acid cycle, and transfer of electrons to generate ATP.

Stage 1: Beta-Oxidation of Saturated Fatty Acids

• Sequential cycles of dehydrogenation, hydration, oxidation, and thiolysis use FAD, NAD+, and CoA.
• Producing Acetyl-CoA and shorter fatty acid chains.

Beta-Oxidation of Saturated Fatty Acids: Energy Balance

• Complete energy yield from palmitic (C16) acid to acetyl-CoA is 129 ATP.
• Each round of beta-oxidation generates 1 FADH2, 1 NADH, and 1 acetyl-CoA.

Monounsaturated Fatty Acid Oxidation

• Additional isomerase step needed for proper beta-oxidation.

Polyunsaturated Fatty Acid Oxidation

• Requires reducing power (NADPH).
• Fewer ATP compared to saturated fatty acids.

Mono/Polyunsaturated Fatty Acid Oxidation: Summary

• Most unsaturated fatty acids have the cis conformation, requiring special enzymes for beta-oxidation.

Oxidation of Odd-Number Fatty Acids

• Odd-number fatty acids yield propionyl-CoA as a final product.
• Propionyl-CoA is converted to succinyl-CoA, allowing entry into the citric acid cycle.
• Coenzyme B12 is necessary for succinyl-CoA formation.

Regulation of Fatty Acid Oxidation

• High glucose levels stimulate malonyl-CoA synthesis.
• Malonyl-CoA inhibits fatty acid transport into mitochondria.

Ketone Bodies – Alternative Fuel to Sugars

• Acetyl-CoA produced from fatty acid oxidation can form ketone bodies: acetoacetate, acetone, and beta-hydroxybutyrate.
• Ketone bodies are alternative fuels for tissues when glucose is unavailable.
• Accumulation results in ketoacidosis.
• Peripheral tissues can't use up ketone bodies fast enough with net acidosis.

Ketone Bodies Formation and Export from the Liver

• Starvation or poorly controlled diabetes leads to excess ketone production.
• Liver converts acetyl-CoA to ketone bodies.
• Ketone bodies are exported as energy sources for other tissues.

Drugs and Diseases

• Diseases: diabetes, diabetic ketoacidosis (metabolic acidosis).
• Drugs and vitamins: epinephrine, vitamin B12, hydroxocobalamin.
• Metabolites: chylomicrons, VLDL, LDL, HDL, ketone bodies.

Explore the intricate processes of fatty acid catabolism and digestion. This quiz covers the transformation of fats from dietary intake to energy sources, detailing the roles of bile salts, lipases, and chylomicrons in fat metabolism. Test your understanding of how fats are utilized by the body for energy and how they are transported.