De Lipideos | Metabolismo

These newly synthesized fatty acids are esterified to glycerol-3-phosphate to form TAGs for storage. They are also incorporated into membrane phospholipids via the Kennedy pathway or by remodeling existing phospholipids (Lands’ cycle). Cholesterol synthesis (isoprenoid pathway) is another critical anabolic component, beginning with HMG-CoA reductase—the target of statin drugs. Cholesterol is essential for membrane fluidity, lipid rafts, and steroid hormone synthesis. The coordinated regulation of lipogenesis, TAG assembly, and cholesterol synthesis by insulin, SREBP (sterol regulatory element-binding proteins), and ChREBP (carbohydrate response element-binding protein) ensures that excess carbon is stored efficiently.

Introduction

Once inside the mitochondrial matrix, β-oxidation proceeds as a four-step cycle (dehydrogenation, hydration, dehydrogenation, thiolysis) that shortens the fatty acid chain by two carbons (acetyl-CoA) per turn. For a saturated 16-carbon palmitate, this yields 8 acetyl-CoA, 7 FADH2, and 7 NADH. The acetyl-CoA enters the TCA cycle for complete oxidation to CO2 and water, generating substantial ATP via oxidative phosphorylation. In times of prolonged fasting or uncontrolled diabetes, however, the liver produces acetyl-CoA in excess of the TCA cycle’s capacity. This surplus is channeled into —the synthesis of ketone bodies (acetoacetate, β-hydroxybutyrate, and acetone). Ketone bodies serve as a water-soluble, alternative fuel for the brain, heart, and muscle, preserving glucose for obligate users like red blood cells. Pathological overproduction leads to ketoacidosis, a life-threatening condition. metabolismo de lipideos

Inside the enterocyte, FFAs and monoacylglycerols are rapidly re-esterified to form TAGs. These, along with newly synthesized cholesteryl esters and phospholipids, are packaged into chylomicrons—the largest and least dense lipoproteins. Chylomicrons enter the lymphatic system (lacteals) and then the bloodstream, delivering dietary lipids to peripheral tissues, particularly adipose tissue and muscle. At the capillary endothelium of these tissues, lipoprotein lipase (LPL) hydrolyzes chylomicron TAGs, releasing FFAs for uptake (storage in adipocytes or oxidation in muscle). The resulting chylomicron remnants, depleted of TAGs, are cleared by the liver via receptor-mediated endocytosis. This hepatic-centric process sets the stage for endogenous lipid metabolism, where the liver produces very-low-density lipoproteins (VLDL) to distribute TAGs synthesized de novo to extrahepatic tissues. These newly synthesized fatty acids are esterified to

Dysregulation of these pathways underlies major diseases. results from chronic positive energy balance, with hypertrophied adipocytes becoming insulin-resistant and releasing excess FFAs (lipotoxicity). Atherosclerosis is driven by retention of apoB-containing lipoproteins (LDL) in artery walls, where they become oxidized, triggering inflammation and plaque formation. NAFLD arises from ectopic TAG accumulation in the liver due to increased lipogenesis and reduced VLDL export, often in the context of insulin resistance. The carnitine shuttle defects cause hypoketotic hypoglycemia and cardiomyopathy in infants. Understanding these pathways has led to effective therapies: statins (HMG-CoA reductase inhibitors), fibrates (PPAR-α activators that enhance fatty acid oxidation), and emerging inhibitors of ACC or SCD1 for NAFLD. Cholesterol is essential for membrane fluidity, lipid rafts,

Inside the cell, FFAs are activated to fatty acyl-CoA by acyl-CoA synthetase. The critical entry step into the mitochondria, where β-oxidation occurs, is mediated by the carnitine shuttle. The enzyme carnitine palmitoyltransferase I (CPT1) is the rate-limiting, regulated step; it converts fatty acyl-CoA to acylcarnitine, which is transported across the inner mitochondrial membrane by translocase and then reconverted to acyl-CoA by CPT2. Malonyl-CoA, the first intermediate in fatty acid synthesis, allosterically inhibits CPT1—a prime example of reciprocal regulation between catabolism and anabolism.

Lipids, broadly defined as hydrophobic or amphipathic biological molecules, are far more than mere passive energy reserves. The term "metabolismo de lípidos" encompasses a complex, highly regulated network of catabolic and anabolic pathways that are fundamental to cellular life. These pathways govern the breakdown of dietary fats for energy (β-oxidation), the synthesis of fatty acids and complex lipids (lipogenesis), and the formation and clearance of lipoproteins for transport. Disruptions in lipid metabolism are central to the pathogenesis of prevalent metabolic diseases, including obesity, atherosclerosis, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). This essay will provide a detailed examination of the core pathways of lipid metabolism—digestion and absorption, transport, catabolism (β-oxidation and ketogenesis), and anabolism (lipogenesis and lipogenesis)—highlighting their biochemical mechanisms, regulatory logic, and physiological integration.