Metabolismo De Lipideos [extra Quality] -
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.
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
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. Dysregulation of these pathways underlies major diseases
