Ketosis

Ketosis is a metabolic state in which some of the body's energy supply comes from ketone bodies in the blood, in contrast to a state of glycolysis in which blood glucose provides energy. Generally, ketosis occurs when the liver is metabolizing fatty acids or ethanol at a high rate in the absence of glucose and converting the product acetyl-CoA into ketone bodies. The first ketone body to be produced is acetoacetate, followed by enzymatic reduction by beta-hydroxybutyrate dehydrogenase to beta-hydroxybutyrate with NADH and a proton as a cofactor, or loss of a carbon dioxide molecule to form acetone. As the liver itself lacks the metabolic machinery required to utilize them, the product ketone bodies are entirely released into the blood for use by the rest of the body. Ketosis is a metabolic state in which some of the body's energy supply comes from ketone bodies in the blood, in contrast to a state of glycolysis in which blood glucose provides energy. Generally, ketosis occurs when the liver is metabolizing fatty acids or ethanol at a high rate in the absence of glucose and converting the product acetyl-CoA into ketone bodies. The first ketone body to be produced is acetoacetate, followed by enzymatic reduction by beta-hydroxybutyrate dehydrogenase to beta-hydroxybutyrate with NADH and a proton as a cofactor, or loss of a carbon dioxide molecule to form acetone. As the liver itself lacks the metabolic machinery required to utilize them, the product ketone bodies are entirely released into the blood for use by the rest of the body. Ketosis is a nutritional process characterised by serum concentrations of ketone bodies over 0.5 mM, with low and stable levels of insulin and blood glucose. It is almost always generalized with hyperketonemia, that is, an elevated level of ketone bodies in the blood throughout the body. Ketone bodies are formed by ketogenesis when liver glycogen stores are depleted (or from metabolising medium-chain triglycerides). Ketones can also be consumed in exogenous ketone foods and supplements. The main ketone bodies used for energy are acetoacetate and β-hydroxybutyrate, and the levels of ketone bodies are regulated mainly by insulin and glucagon. Most cells in the body can use both glucose and ketone bodies for fuel, and during ketosis, free fatty acids and glucose synthesis (gluconeogenesis) fuel the remainder. Longer-term ketosis may result from fasting or staying on a low-carbohydrate diet (ketogenic diet), and deliberately induced ketosis serves as a medical intervention for various conditions, such as intractable epilepsy, and the various types of diabetes. In glycolysis, higher levels of insulin promote storage of body fat and block release of fat from adipose tissues, while in ketosis, fat reserves are readily released and consumed. For this reason, ketosis is sometimes referred to as the body's 'fat burning' mode. The difference between ketosis and ketoacidosis is the level of ketones in the blood. Ketosis is a physiological adaptation to a low carbohydrate environment like fasting or a ketogenic diet. There are situations (such as treatment-resistant epilepsy) where ketosis can be beneficial to health. Ketoacidosis is an acute life-threatening state requiring prompt medical intervention; its most common form is diabetic ketoacidosis where both glucose and ketone levels are significantly elevated. Ketone bodies are acidic, but acid-base homeostasis in the blood is normally maintained through bicarbonate buffering, respiratory compensation to vary the amount of CO2 in the bloodstream, hydrogen ion absorption by tissue proteins and bone, and renal compensation through increased excretion of dihydrogen phosphate and ammonium ions. Prolonged excess of ketone bodies can overwhelm normal compensatory mechanisms, defined as acidosis if blood pH falls below 7.35.