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.
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. metabolismo de lipideos
When energy and carbohydrate intake exceed immediate needs, the liver and adipose tissue convert excess acetyl-CoA into fatty acids via . This pathway occurs in the cytoplasm. The key regulated enzyme is acetyl-CoA carboxylase (ACC), which converts acetyl-CoA to malonyl-CoA. ACC is activated by citrate (a sign of abundant energy) and insulin, and inhibited by AMPK (energy stress) and glucagon. The fatty acid synthase (FAS) complex, a large multienzyme protein, then uses NADPH (supplied primarily by the pentose phosphate pathway) to extend the malonyl-CoA-derived two-carbon units into palmitate. Further elongation and desaturation (introducing double bonds via desaturases like SCD1) yield the diverse spectrum of cellular fatty acids. 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,
Introduction
When energy demands rise or glucose is scarce (e.g., fasting, exercise), fatty acids become the primary fuel. Hormone-sensitive lipase (HSL) in adipose tissue is activated by glucagon and epinephrine, liberating FFAs into the bloodstream. FFAs, bound to serum albumin, are transported to oxidative tissues like heart, skeletal muscle, and liver.
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.