Ketogén

Ketogén refers to ketogenesis or the ketogenic state, in which ketone bodies are produced as an energy source during periods of limited carbohydrate intake. The main ketone bodies are acetoacetate, beta-hydroxybutyrate, and acetone. They are produced primarily in the liver’s mitochondria from acetyl-CoA derived from fatty acid oxidation. When glucose availability is low, oxaloacetate is diverted to gluconeogenesis, limiting the entry of acetyl-CoA into the TCA cycle. Excess acetyl-CoA is then diverted into ketogenesis, yielding acetoacetate, which can be reduced to beta-hydroxybutyrate or decarboxylate to acetone. Ketone bodies are released into the bloodstream and used by peripheral tissues as an alternative energy source.

Key enzymes involved include HMG-CoA synthase 2 and HMG-CoA lyase in hepatocytes. Ketone bodies are transported to other tissues and converted back to acetyl-CoA by enzymes such as BDH1 to fuel cellular respiration. Hormonal regulation involves insulin, which inhibits ketogenesis, and glucagon, epinephrine, and norepinephrine, which promote it by stimulating lipolysis and increasing fatty acid supply to the liver.

Physiological contexts: fasting, prolonged exercise, pregnancy, and very-low-carbohydrate diets can raise ketone production. In untreated type 1 diabetes, excessive ketogenesis can lead to ketoacidosis, a dangerous condition. Ketosis from fasting or diet is a normal adaptive response, whereas ketoacidosis is pathological and requires medical attention.

Clinical and dietary relevance: the ketogenic diet is a high-fat, very-low-carbohydrate regimen used therapeutically for certain conditions, notably refractory epilepsy and some metabolic disorders. Long-term adherence should consider potential dehydration, electrolyte imbalances, kidney stones, and micronutrient deficiencies. Distinguishing physiological ketosis from diabetic or alcoholic ketoacidosis is important for appropriate management.