Fatty Acid Catabolism & Energy Storage

Fatty Acid Catabolism

• Fatty acids are catabolized, and their inherent energy is captured by organisms

Energy Storage

• Fatty acids are used by organisms for energy storage due to two reasons: reduced carbon and non-hydrated nature
• Carbon in fatty acids (mostly -CH2-) is reduced, so its oxidation yields the most energy possible
• Fatty acids are not hydrated like mono- and polysaccharides, allowing them to pack more closely in storage tissues

Mobilization of Fats

• "Fats" in diet and adipose tissue predominantly consist of triglycerides
• Triglycerides are a major energy input in the modern American diet
• Triglycerides are the major form of stored energy in the body
• Hormones such as glucagon, epinephrine, and ACTH trigger the release of fatty acids from adipose tissue

Fat Digestion

• Pancreatic lipases and PLA2 break down triacylglycerols (TAGs)
• After absorption, these are reconstituted

Fatty Acid Breakdown

• Knoop discovered that fatty acids are degraded by removing 2-carbon units
• Albert Lehninger discovered that this degradation occurs in the mitochondria
• F. Lynen and E. Reichart found that the 2-carbon unit released is acetyl-CoA, not free acetate
• The breakdown process starts with oxidation of the carbon that is "ẞ" to the carboxyl carbon, known as "ẞ-oxidation"

CoA Activation

• Acyl-CoA synthetase condenses fatty acids with CoA, hydrolyzing ATP to AMP and PPi
• Formation of a CoA ester is energetically expensive
• Free energy change barely breaks even with ATP hydrolysis
• Subsequent hydrolysis of PPi drives the reaction strongly forward
• The mechanism includes an acyl-adenylate intermediate

Carnitine as a Carrier

• Carnitine transports fatty acyl groups across the mitochondrial membranes
• Short-chain fatty acids are directly transported into the mitochondrial matrix
• Long-chain fatty acids cannot be directly transported into the matrix
• Instead, long-chain fatty acids are converted to acyl-carnitines and then transported into the mitochondria
• Acyl-CoA esters are formed inside the inner mitochondrial membrane from transported acylcarnitines

β-Oxidation

• Key steps in β-oxidation involve a repeated sequence of 4 reactions
• The strategy is to create a carbonyl group at the β-carbon
• The first 3 reactions achieve this
• The fourth reaction cleaves the "β-keto ester" in a reverse Claisen condensation
• Products are acetyl-CoA and a fatty acid that is two carbons shorter
• The first three reactions are crucial and classic, repeating in other pathways

Acyl-CoA Dehydrogenases

• Are a family of membrane-bound and soluble matrix enzymes
• As a fatty acyl chain shortens through β-oxidation cycles, it moves from the membrane-bound complex to soluble matrix enzymes
• The Acyl-CoA dehydrogenase mechanism involves proton abstraction, followed by double-bond formation and hydride removal by FAD
• Electrons are passed to an electron transfer flavoprotein (ETF), and then to the electron transport chain