The production and utilization of ketones.

acetone body(acetone bodies) is a special intermediate product of fatty acids produced by normal decomposition metabolism in the liver, including acetylacetic acid (about 30%), β-hydroxybutyric acid (beta hydroxybutyric acid about 70%) and very small amounts of acetone (acetone). Normal people have very little ketone in their blood (about 0.8?). 0mg/dl, 0.22mM), which is normal for the human body to use fat oxidation for energy supply. However, in certain physiological conditions (hunger, fasting) or pathological conditions (e.g. diabetes), the source of sugar or oxidative energy supply disorders, fat mobilization increases, fatty acids become the body's main energy supply.
If the amount of synthetic ketones in the liver exceeds the ability of the
tissues outside the liver
to utilize the ketone body, the balance between the two is lost and the blood concentration is too high, leading to ketoemia (acetonemia) and ketoaemia (acetonuria). Acetylacetic acid and β-hydroxybutyric acid are acidic substances, so the accumulation of ketones in the body can also cause acidosis. . 1. Ketone production process:ketones are produced in the mitochondrials of liver cells, the raw material is fatty acids β-oxidation-generated acetylCoA. The first is the dimolecules acetylCoA in the action of sulfur dissociase to take off a molecule coenzyme A, the production of acetylCoA.at hydroxy-3-methyl diamide CoA (hydroxy methyl glutarylCoA, HMGCoA) synthase catalysis, acetylCoA reacts with a molecule of acetylCoA to produce HMGCoA and releases a molecule of coenzyme. This step is a speed limit step for ketone body production.. HMG-CoA lysis enzymes catalyz HMG-CoA to produce acetyl acetic acid and acetyl CoA, which can then be used for the synthesis of ketones.β-hydroxybutyric acid
dehydrogenase
catalytic acetic acid hydrodygenation reduction (NADH-H-plus hydrogenation) in the mitochondrials to produce β-hydroxybutyric acid, which is determined by the ratio of the mitochondrial to the ratio of the mitochondrials to the production of acetone by a small amount of acetic acid.the above ketone body generation process is actually a circular process, also known as the lynen cycle, through which two molecules acetylCoA produce a molecule of acetylacetic acid.ketone body is rapidly passed through the hepato mitochondrial membrane and cell membrane into the blood, transported to the liver tissue for use.. 2. The utilization process of ketone bodiesthere is amber coa thiophorase (succinyl Coa thiophorase) in the skeletal muscle, heart muscle and kidneys, which catalyzed acetyl acetic acid to produce acetylCoA when amber CoA was present.also have sulfur
kinase
in the heart muscle, kidneys and brain, which catalytic acetylate acid is active into acetylCoA when ATP and coenzyme T are present.acetylCoA, which is catalyzed by the two enzymes mentioned above, is broken down into two molecules, acetylCoA, which is mainly oxidized and decomposed by the triacetic acid cycle.acetone is excreted with urine, a portion is exhaled directly from the lungs and does not metabolically play an important role, and the process of using acetylacetic acid and β-hydroxybutyric acid in liver tissue can be indicated in the figure below.there is no amber coA transthionase and acetylacetic acid sulfur kinase in liver cells, so liver cells cannot use ketones.the amount of ketones used in extra-liver tissue is directly related to the concentration of ketones in arterial blood, and the utilization capacity of extra-liver tissue reaches saturation when the concentration of extra-hepatic tissue reaches 70 mg/dl. The renal ketone threshold is also 70 mg/dl, the concentration of ketones in the blood exceeds this value, the filtration of ketones through the kidney sphere exceeds the re-absorption capacity of the renal tube, ketouria occurs. The ability of brain tissue to use ketones is associated with blood sugar levels, which are used only when blood sugar levels drop.. 3. Meaning of ketone body production (1) Ketone body easy transport: long-chain fatty acids through the mitochondrial membrane need carrier carnitine transport, fatty acid transport in the blood needs to be combined with albumin to produce lipid albumin, and ketone body through mitochondrial membrane and blood transport does not need carrier. (2) easy to use: fatty acids after bio-oxidation into β-oxidation, every 4 steps of reaction to produce a molecule of acetylCoA, and acetylacetic acid after the activity of only one step can produce two molecules of acetylCoA, β-hydroxybutyric acid utilization is only one step more oxidation reaction than acetylacetic acid. Therefore, ketones can be thought of as semi-finished products produced by fatty acids processed in the liver. (3) Save glucose for use by the brain and red blood cells: extra-hepatic tissue uses ketones to produce a large amount of acetylCoA, a large amount of acetylCoA inhibits the activity of acetone acid dehydrogenase system, limiting the use of sugar. At the same time, acetylCoA can also activate acetone acetate pyrase, promoting sugar isoenzyme. The use of oxidation of ketones to supply energy in liver tissue reduces the need for glucose to ensure the need for glucose in brain tissue and red blood cells. Brain tissue can not use long-chain fatty acids, but when hungry can use ketone body energy, hunger 5 weeks ketone body supply can be up to 70%. (4) muscle tissue using ketones can inhibit the breakdown of muscle
protein
and prevent excessive protein consumption, the action of which is not clear. (5) increase in ketone production is common in cases of hunger, pregnancy poisoning, diabetes, etc. A low-sugar, high-fat diet can also increase ketone production.


. .