What Are Ketone Bodies?

Ketone bodies are collectively known as acetoacetic acid, -hydroxybutyric acid, and acetone, which are intermediate products of oxidative decomposition of fatty acids in the liver. So ketone bodies are the breakdown products of fat, not glucose. The detection of blood ketone bodies is mainly used to screen, detect, and monitor ketoacidosis (DKA) for type 1 and sometimes type 2 diabetes ^[1] . The liver has a strong ketone body enzyme system, but lacks an enzyme system that utilizes ketone bodies.

Ketone bodies are intermediate metabolites in the process of fat oxidation metabolism, including acetoacetic acid, -hydroxybutyric acid, and acetone. In healthy humans, a small amount of ketone bodies are present in the blood at a ratio of 78% -hydroxybutyric acid, 20% acetoacetic acid, and 2% acetone. When the rate of production of ketones in the liver exceeds the rate of utilization of extrahepatic tissues, blood ketones increase, and ketonemia may occur, and excessive ketones are excreted from the urine to form ketonuria ^[2]

Ketone bodies are fuel of many tissues including the brain during starvation, and therefore have important physiological significance.

Once fatty acids are degraded in the liver mitochondria, the resulting acetyl CoA can have several metabolic consequences. The most important thing is of course that it enters the citric acid cycle and further electron transfer systems, and finally completely oxidizes to CO ₂ and H ₂ 0; the second is as a precursor of steroids, which generates cholesterol, which is the starting compound in cholesterol biosynthesis; The third is to play the role of precursor of fatty acid synthesis. The fourth is to convert it into acetoacetic acid, D--hydroxybutyric acid and acetone. These three compounds are collectively called ketone body.

Ketone body synthesis is primarily a function of the liver. The amount of acetone produced in the ketone body is relatively small and is absorbed immediately after the formation. Acetoacetic acid and D-beta-hydroxybutyric acid enter the extrahepatic tissues through the bloodstream, where they are oxidized, and provide more energy for those tissues such as bone, heart muscle, and kidney cortex through the citric acid cycle. Brain tissue generally only uses glucose as fuel, but when starved, glucose is inadequate. It can accept acetoacetic acid or D--hydroxybutyric acid ^[5]

1. Hydroxybutyric acid can be produced by oxidation of hydroxybutyric acid dehydrogenase

NEFA in the liver is the main source of ketone bodies. In plasma

Diabetic ketonuria, only seen in advanced severe diabetes, is

There are several aspects to prevent the production of ketone bodies:

1.Precautions

In different types

1. Ketone bodies are easy to transport: Long-chain fatty acids need to be transported by the carrier carnitine through the mitochondrial inner membrane. Fatty acids need to be combined with albumin to produce fatty acid albumin for transport in the blood, while ketone bodies are transported through the mitochondrial inner membrane and in the blood No carrier is needed.

2. Easy to use: fatty acid enters -oxidation, every 4 steps of reaction can generate one molecule of acetyl CoA, and acetoacetic acid only needs one step of reaction to generate two molecules of acetyl CoA. The use of -hydroxybutyric acid is only One more oxidation reaction than acetoacetate. Therefore, ketone bodies can be regarded as semi-finished products produced by fatty acids in the liver.

3. Save glucose for brain and red blood cell utilization: The use of ketone bodies in extrahepatic tissues will generate a large amount of acetyl CoA. A large amount of acetyl CoA inhibits the activity of pyruvate dehydrogenase and limits the use of sugar. At the same time, acetyl CoA can also activate pyruvate carboxylase and promote gluconeogenesis. Extrahepatic tissues use ketone bodies to oxidize energy, reducing the need for glucose to ensure that the brain and red blood cells need glucose. Brain tissue cannot utilize long-chain fatty acids, but can be powered by ketone bodies when starved, starvation 5? Ketone body energy can be as high as 70% per week.

4. The use of ketones in muscle tissues can inhibit the breakdown of muscle proteins and prevent excessive protein consumption. The mechanism of action is unknown.

5. Increased ketone body production is common in hunger, pregnancy poisoning, and diabetes. Low sugar and high fat diet can also increase ketone body production. When the amount of ketones produced in the liver exceeds the utilization capacity of extrahepatic tissues, the ketones in the blood can be increased, which is called ketemia, and if ketemia occurs in the urine, it is called ketonuria.

1. Effects of satiety and hunger: After satiety, insulin secretion increases, lipolysis is inhibited, fat mobilization is reduced, fatty acid entering the liver is reduced, and ketone body production is reduced. When hungry, secretion of glucagon and other lipolytic hormones increases, fatty acid mobilization is enhanced, and free fatty acid concentration in the blood increases, which increases free fatty acid uptake by the liver, which is beneficial to fatty acid -oxidation and ketone body production ^[3] .

2. The effect of glycogen content and metabolism of hepatocytes: There are two main ways for free fatty acid entering hepatocytes. One is esterification in cytosol to synthesize triglycerides and phospholipids; the other is to enter mitochondria for -oxidation. Generates acetyl-CoA (acetyl CoA) and ketone bodies. When full food and sugar supply are sufficient, liver glycogen is abundant and sugar metabolism is vigorous. At this time, the fatty acid that enters liver cells is mainly esterified with glycerol 3-phosphate and reacted to produce triglycerides and phospholipids. When starvation or insufficient sugar supply, sugar metabolism is reduced, glycerol 3-phosphate and ATP are insufficient, fatty acidification is reduced, mainly enters the mitochondria for oxidation, and ketone bodies increase ^[3] .

3. Malonyl CoA inhibits fatty acyl CoA from entering mitochondria: Acetyl CoA and citric acid generated when sugar metabolism proceeds normally after satiety can allosterically activate acetyl CoA carboxylase and promote the synthesis of malonyl CoA. The latter can competitively inhibit carnitine fatty acyltransferase I, thereby preventing fatty acyl-CoA from entering the mitochondria for -oxidation ^[3] .