15: Lipids Catabolism

Digestion of Fatty Foods

    When you eat foods rich in fat—like burgers, fried chicken, pizza, or peanut butter—your body begins the process of digesting and absorbing these fats so they can be used for energy, hormone production, or storage. The primary form of fat in food is the triglyceride, which is made up of three fatty acids attached to a glycerol backbone. However, triglycerides are large, hydrophobic (water-fearing) molecules, and our digestive system is water-based. Therefore, the body needs special strategies to process and absorb them.

    Digestion begins in the stomach, where an enzyme called gastric lipase starts the preliminary breakdown of triglycerides. However, this enzyme is not very efficient and acts mostly on short- and medium-chain triglycerides (like those found in milk). This step is minimal and mainly prepares the fats for further digestion. Most fat digestion happens in the small intestine, especially in the duodenum, where powerful enzymes and bile are released. The pancreas secretes an enzyme called pancreatic lipase, which is specialized in breaking down triglycerides. But before the enzyme can act, bile salts from the liver and gallbladder emulsify the fat droplets—breaking them into much smaller droplets called micelles. This emulsification increases the surface area for pancreatic lipase to work efficiently. Pancreatic lipase then hydrolyzes triglycerides into 2 free fatty acids and 1 monoacylglycerol (a glycerol with one fatty acid still attached). These smaller units are small and hydrophobic enough to be absorbed by enterocytes, the epithelial cells lining the small intestine.

    Once absorbed into the enterocytes, these components are re-esterified—reassembled back into full triglycerides. But since triglycerides are still too hydrophobic to travel through the watery blood, they are packed into chylomicrons, which are large, spherical lipoprotein particles made of triglycerides, cholesterol, and proteins, which act as transport carriers.

Transport and Storage of Lipids

    After their assembly into lipoprotein, triglycerides leave the intestinal cells and enter the lymphatic system—not the bloodstream right away. This is because lipoprotein are too large to enter the small blood capillaries. Instead, they are taken up by lymph vessels, which eventually dump their contents into the thoracic duct, which connects to the subclavian vein, allowing entry into the bloodstream.

     Once in the bloodstream, lipoprotein delivers triglycerides to various tissues, including Muscle cells, which use the triglycerides for energy (especially during exercise or fasting), and Adipose (fat) tissue, which stores them for later use when energy is scarce. To facilitate this delivery, an enzyme called lipoprotein lipase (LPL)—anchored on the surface of capillaries—breaks down the triglycerides again into free fatty acids, which can then enter muscle or fat cells.

    In fat cells, the fatty acids are again reassembled into triglycerides and stored in lipid droplets. These droplets can expand or shrink based on your body's energy demands. When you're in a fasted state, triglycerides in these droplets are broken down (lipolysis) to release fatty acids into the bloodstream for use.

    Besides transporting triglycerides, lipoproteins are crucial for cholesterol homeostasis. Two types of lipoproteins are most relevant: LDL and HDL. LDL particles carry cholesterol from the liver to peripheral tissues. This is essential because cholesterol is a building block for cell membranes and steroid hormones. However, when LDL is oxidized (especially due to smoking, poor diet, or stress), it becomes dangerous. Oxidized LDL is taken up by immune cells called macrophages, which then become foam cells—lipid-laden cells that accumulate inside blood vessel walls. Over time, these form plaques, leading to atherosclerosis and increased risk of heart attack or stroke. HDL particles work in reverse—they collect excess cholesterol from tissues and blood vessels and bring it back to the liver for excretion. This protective action helps clear the bloodstream and prevents plaque buildup.

     Statins like Atorvastatin (Lipitor) help lower LDL cholesterol. They work by inhibiting HMG-CoA reductase, an enzyme the liver uses to make cholesterol, and upregulating LDL receptors on liver cells, allowing the liver to pull more LDL out of circulation. This dual action lowers blood LDL levels and reduces the risk of cardiovascular diseases. If someone has high cholesterol and their doctor prescribes Lipitor, it helps reduce LDL in their blood and prevent artery plaque formation—protecting against heart disease.

Fatty Acid Activation

    Before your cells can use fatty acids for energy, the fatty acids need to be activated. This process occurs in the cytoplasm and involves "tagging" the fatty acid with a molecule of Coenzyme A (CoA), creating a compound called fatty acyl-CoA. This activation step is catalyzed by the enzyme acyl-CoA synthetase (also known as thiokinase), and it requires energy from ATP: Fatty Acid + CoA + ATP → Fatty Acyl-CoA + AMP + PPi

    This reaction uses 2 high-energy phosphate bonds because ATP is converted to AMP (not ADP), and pyrophosphate (PPi) is quickly broken down to drive the reaction forward, making it essentially irreversible.

Once formed, fatty acyl-CoA has two major fates:

1. Biosynthesis: It can be used to make structural lipids, such as phospholipids, sphingolipids, or waxes—important in membranes, skin, and signaling molecules.
2. Energy production: It can be transported into the mitochondrial matrix for β-oxidation, a catabolic process that breaks down fatty acids to produce ATP.

    What About Glycerol? When triglycerides are broken down (especially during fasting or prolonged exercise), glycerol is released alongside fatty acids. Glycerol, being water-soluble, travels through the bloodstream to the liver, where it has two potential fates:

1. It can enter glycolysis, being converted into pyruvate, which can then become acetyl-CoA or lactate.
2. Or, it can enter gluconeogenesis, the pathway to generate glucose, helping maintain blood sugar levels during fasting.

β-Oxidation

    Once inside the mitochondria, fatty acyl-CoA enters the β-oxidation cycle, which is the process that breaks down fatty acids two carbons at a time, producing acetyl-CoA, NADH, and FADH₂ in each cycle. This process continues until the entire fatty acid chain is chopped into two-carbon units. Each round of β-oxidation includes four key steps, each catalyzed by a specific enzyme.

Unsaturated Fatty Acids

    Unsaturated fats (like oleic acid or linoleic acid found in olive oil and nuts) have pre-existing double bonds, which skip the first oxidation step in β-oxidation. Because the first oxidation step produces FADH₂, skipping it means you lose the ATP that FADH₂ would’ve generated. So, for each double bond in an unsaturated fatty acid, you will miss out on 1 FADH₂ = 2 ATP lost. Thus, A 12-carbon unsaturated fatty acid with one double bond yields: 85 ATP – 2 ATP (for skipped FADH₂) = ~83 ATP 

    Though unsaturated fats give slightly less ATP, they are healthier for cardiovascular health and have other metabolic benefits (like modulating inflammation and membrane fluidity).

Summary Table: Beta-Oxidation of a 12-Carbon Fatty Acid