Various types of lipids occur in the human body, namely This chapter will focus on triacylglycerol; cholesterol will be covered in a separate chapter. The metabolism of polar lipids will not be covered systematically. In contrast to polar lipids and cholesterol, which are found in the membranes of every cell, triacylglycerol is concentrated mostly in adipose (fat) tissue; minor amounts of triacylglycerol occur in other cell types, such as liver epithelia and skeletal muscle fibers. Yet, overall, triacylglycerol is the most abundant lipid species, and the only one with an important role in energy metabolism. Triacylglycerol occurs in human metabolism in two roles, namely1)as a foodstuff, which accounts for a significant fraction of our caloric intake, and 2)as a store of metabolic energy. This store can be replenished using dietary triacylglycerol or through endogenous synthesis from carbohydrates or proteins. The amount of energy stored per gram of tissue is far higher in fat than in any other tissue, for two reasons: 1.One gram of triacylglycerol itself contains more than twice as many calories as one gram of carbohydrates or protein. This is simply because triacylglycerol contains much less oxygen than carbohydrates, in which oxygen contributes half the mass but essentially no metabolic energy. Similarly, the oxygen, nitrogen and sulfur contained in protein detract from its energy density. 2.Triacylglycerol in fat cells coalesces to droplets that are entirely free of water. In contrast, protein and carbohydrates, including glycogen, always remain hydrated, which further diminishes the density of energy storage. Because of its high energy density, it makes sense that most of the excess glucose or protein is converted to fat, while only a limited fraction is stored as g Continue reading >>
Ketone Bodies: Formation And Utilisation | Living Organisms | Biology
ADVERTISEMENTS: In this article we will discuss about:- 1. Formation of Ketone Bodies 2. Conditions Leading to Ketosis 3. Source 4. Utilisation 5. Interrelation with Carbohydrate Metabolism 6. Ratio 7. Relation of Ketosis with Blood and Urine Reaction 8. Role of Endocrine. Formation of Ketone Bodies (Ketogenesis): It has been observed that acetyl CoA produced during fatty acid oxidation condense with oxalo-acetic acid for oxidation in the TCA cycle. The oxalo-acetic acid formation is depressed when glucose supply is restricted so that in this condition acetyl CoA cannot be properly metabolized through citric acid cycle. Thus acetyl CoA condenses to form aceto-acetyl CoA which in the liver produces aceto-acetic acid. The aceto-acetic acid is reduced to form β-hydroxybutyric acid which after decarboxylation forms acetones. Acetoacetic acid, acetone and β-hydroxybutyric acid are called ketone bodies. The process of formation of ketone bodies is called ketogenesis. Normally the ketone bodies are utilized without being accumulated in the body, but they may be abnormally accumulated in body fluids known as ketosis and excreted through the urine called ketonuria (or acetonuria). Its accumulation in the blood is called ketonemia. Site of Formation of Ketone Bodies: Liver is perhaps the only site where ketone bodies are normally formed since concentration of ketone bodies have been found to be higher in the hepatic vein than in other veins. Antiketogenic Substances: These are substances which prevent the formation of ketone bodies. They include the following: (1) All carbohydrates, (2) 60% of proteins (antiketogenic amino acids) from which sugar may be formed and (3) 10% of fats (the glycerol part) Conditions Leading to Ketosis: The following conditions produce ketosis: (a) Di Continue reading >>
There is a lot of confusion about the term ketosis among medical professionals as well as laypeople. It is important to understand when and why nutritional ketosis occurs, and why it should not be confused with the metabolic disorder we call ketoacidosis. Ketosis is a metabolic state where the liver produces small organic molecules called ketone bodies. Most cells in the body can use ketone bodies as a source of energy. When there is a limited supply of external energy sources, such as during prolonged fasting or carbohydrate restriction, ketone bodies can provide energy for most organs. In this situation, ketosis can be regarded as a reasonable, adaptive physiologic response that is essential for life, enabling us to survive periods of famine. Nutritional ketosis should not be confused with ketoacidosis, a metabolic condition where the blood becomes acidic as a result of the accumulation of ketone bodies. Ketoacidosis can have serious consequences and may need urgent medical treatment. The most common forms are diabetic ketoacidosis and alcoholic ketoacidosis. What Is Ketosis? The human body can be regarded as a biologic machine. Machines need energy to operate. Some use gasoline, others use electricity, and some use other power resources. Glucose is the primary fuel for most cells and organs in the body. To obtain energy, cells must take up glucose from the blood. Once glucose enters the cells, a series of metabolic reactions break it down into carbon dioxide and water, releasing energy in the process. The body has an ability to store excess glucose in the form of glycogen. In this way, energy can be stored for later use. Glycogen consists of long chains of glucose molecules and is primarily found in the liver and skeletal muscle. Liver glycogen stores are used to mai Continue reading >>
Ketone Body Formation
Ketone body formation occurs as an alternative energy source during times of prolonged stress e.g. starvation. It occurs in the liver from an initial substrate of: long chain fatty acids; the fatty acids undergo beta-oxidation by their normal pathway within mitochondria until acetyl-CoA is produced, or ketogenic amino acids; amino acids such as leucine and lysine, released at times of energy depletion, are interconverted only to acetyl-CoA Then, three molecules of acetyl-CoA are effectively joined together in three enzyme steps sequentially catalyzed by: acetyl CoA acetyltransferase HMG-CoA transferase HMG-CoA lyase Coenzyme A is regenerated and the ketone body acetoacetate is formed. Finally, acetoacetate is reduced to another ketone body, D-3-hydroxybutyrate, in a reaction catalyzed by 3-hydroxybutyrate dehydrogenase. This requires NADH. The oxidate state of the liver is such that the forward reaction is generally favoured; this results in more hydroxybutyrate being formed than acetoacetate. Continue reading >>
What is Ketogenesis? Ketogenesis (1, 2) is a biochemical process that produces ketone bodies by breaking down fatty acids and ketogenic amino acids. The process supplies the needed energy of certain organs, especially the brain. Not having enough ketogenesis could result to hypoglycaemia and over production of ketone bodies leading to a condition called ketoacidosis. It releases ketones when fat is broken down for energy. There are many ways to release ketones such as through urination and exhaling acetone. Ketones have sweet smell on the breath. (3) Ketogenesis and ketoacidosis are entirely different thing. Ketoacidosis is associated with diabetes and alcoholism, which could lead to even serious condition like kidney failure and even death. Picture 1 : Ketogenic pathway Photo Source : medchrome.com Image 2 : A pyramid of ketogenic diet Photo Source : www.healthline.com What are Ketone bodies? Ketone bodies are water soluble molecules produced by the liver from fatty acids during low food intake or fasting. They are also formed when the body experienced starvation, carbohydrate restrictive diet, and prolonged intense exercises. It is also possible in people with diabetes mellitus type 1. The ketone bodies are picked up by the extra hepatic tissues and will convert to acetyl-CoA. They will enter the citric acid cycle and oxidized in the mitochondria to be used as energy. Ketone bodies are needed by the brain to convert acetyl-coA into long chain fatty acids. Ketone bodies are produced in the absence of glucose. (1, 2, 3) It is easy to detect the presence of ketone bodies. Just observe the person’s breath. The smell of the breath is fruity and sometimes described as a nail polish remover-like. It depicts the presence of acetone or ethyl acetate. The ketone bodies includ Continue reading >>
Diabetic Ketoacidosis- Enzyme For Ketones Formation?
Case details A 54- year-old man with Type 1 diabetes is referred to an ophthalmologist for evaluation of developing cataract. Blood chemistry results are shown below- Fasting blood glucose 198 mg/dl Hemoglobin A 15 gm/dl Hemoglobin A 1c 10% of total Hb Urine ketones Positive Urine glucose Positive Which of the following enzymes is most strongly associated with ketones formation in this patient? A) Pyruvate dehydrogenase complex B) Thioesterase C) Thiophorase D) Thiokinase E) Thiolase. The correct answer is- E- Thiolase. Out of the given options thiolase is the only enzyme involved in the ketogenesis. The process of ketogenesis starts from the action of thiolase. In fact, the actual specific enzyme for ketogenesis is HMG Co A Synthase (mitochondrial isoform) which is not mentioned in the given options. Ketone bodies Acetoacetate, D (-3) -hydroxybutyrate (Beta hydroxy butyrate), and acetone are often referred to as ketone bodies (figure-1). Figure-1- Acetoacetate is the primary ketone body, the other ketone bodies are derived from it. The term “ketones” is actually a misnomer because beta-hydroxybutyrate is not a ketone and there are ketones in blood that are not ketone bodies, e.g., pyruvate, fructose. Ketogenesis takes place in liver using Acetyl co A as a substrate or a precursor molecule. Enzymes responsible for ketone body formation are associated mainly with the mitochondria. Steps of synthesis Acetoacetate (First ketone body) is formed from acetyl CoA in three steps (Figure-2). 1) Two molecules of acetyl CoA condense to form Acetoacetyl CoA. This reaction, which is catalyzed by thiolase, is the reverse of the thiolysis step in the oxidation of fatty acids. 2) Acetoacetyl CoA then reacts with acetyl CoA and water to give 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) Continue reading >>
Ketone Body Metabolism
Ketone body metabolism includes ketone body synthesis (ketogenesis) and breakdown (ketolysis). When the body goes from the fed to the fasted state the liver switches from an organ of carbohydrate utilization and fatty acid synthesis to one of fatty acid oxidation and ketone body production. This metabolic switch is amplified in uncontrolled diabetes. In these states the fat-derived energy (ketone bodies) generated in the liver enter the blood stream and are used by other organs, such as the brain, heart, kidney cortex and skeletal muscle. Ketone bodies are particularly important for the brain which has no other substantial non-glucose-derived energy source. The two main ketone bodies are acetoacetate (AcAc) and 3-hydroxybutyrate (3HB) also referred to as β-hydroxybutyrate, with acetone the third, and least abundant. Ketone bodies are always present in the blood and their levels increase during fasting and prolonged exercise. After an over-night fast, ketone bodies supply 2–6% of the body's energy requirements, while they supply 30–40% of the energy needs after a 3-day fast. When they build up in the blood they spill over into the urine. The presence of elevated ketone bodies in the blood is termed ketosis and the presence of ketone bodies in the urine is called ketonuria. The body can also rid itself of acetone through the lungs which gives the breath a fruity odour. Diabetes is the most common pathological cause of elevated blood ketones. In diabetic ketoacidosis, high levels of ketone bodies are produced in response to low insulin levels and high levels of counter-regulatory hormones. Ketone bodies The term ‘ketone bodies’ refers to three molecules, acetoacetate (AcAc), 3-hydroxybutyrate (3HB) and acetone (Figure 1). 3HB is formed from the reduction of AcAc i Continue reading >>
Diabetes And Ketones
Tweet The presence of high levels of ketones in the bloodstream is a common complication of diabetes, which if left untreated can lead to ketoacidosis. Ketones build up when there is insufficient insulin to help fuel the body’s cells. High levels of ketones are therefore more common in people with type 1 diabetes or people with advanced type 2 diabetes. If you are suffering from high levels of ketones and seeking medical advice, contact your GP or diabetes healthcare team as soon as possible. What are ketones? Ketones are an acid remaining when the body burns its own fat. When the body has insufficient insulin, it cannot get glucose from the blood into the body's cells to use as energy and will instead begin to burn fat. The liver converts fatty acids into ketones which are then released into the bloodstream for use as energy. It is normal to have a low level of ketones as ketones will be produced whenever body fat is burned. In people that are insulin dependent, such as people with type 1 diabetes, however, high levels of ketones in the blood can result from taking too little insulin and this can lead to a particularly dangerous condition known as ketoacidosis. How do I test for ketones? Ketone testing can be carried out at home. The most accurate way of testing for ketones is to use a blood glucose meter which can test for ketones as well as blood glucose levels. You can also test urine for ketone levels, however, the testing of urine means that the level you get is representative of your ketone levels up to a few hours ago. Read about testing for ketones and how to interpret the results Who needs to be aware of ketones? The following people with diabetes should be aware of ketones and the symptoms of ketoacidosis: Anyone dependent on insulin – such as all people Continue reading >>
Ketosis, Ketone Bodies, And Ketoacidosis – An Excerpt From Modern Nutritional Diseases, 2nd Edition
The following text is excerpted from Lipids (Chapter 8) of Modern Nutritional Diseases, 2nd Edition. Ketone Bodies and Ketosis: Ketones are organic chemicals in which an interior carbon in a molecule forms a double bond with an oxygen molecule. Acetone, a familiar chemical, is the smallest ketone possible. It is composed of three carbons, with the double bond to oxygen on the middle carbon. Biological ketone bodies include acetone, larger ketones, and biochemicals that can become ketones. The most important of the ketone bodies are hydroxybutyrate and acetoacetate, both of which are formed from condensation of two acetyl CoA molecules. Acetone is formed from a nonenzymatic decarboxylation of acetoacetate. Ketone bodies are fuel molecules that can be used for energy by all organs of the body except the liver. The production of ketone bodies is a normal, natural, and important biochemical pathway in animal biochemistry (17, p. 577). Small quantities of ketone bodies are always present in the blood, with the quantity increasing as hours without food increase. During fasting or carbohydrate deprivation, larger amounts of ketone bodies are produced to provide the energy that is normally provided by glucose. Excessive levels of circulating ketone bodies can result in ketosis, a condition in which the quantity of circulating ketone bodies is greater than the quantity the organs and tissues of the body need for energy. People who go on extremely low-carbohydrate diets to lose a large excess of body fat usually go into a mild ketosis that moderates as weight is lost. There is no scientific evidence that a low-carbohydrate diet is capable of producing sufficient ketone bodies to be harmful. Excess ketone bodies are excreted by the kidneys and lungs. Exhaled acetone gives the brea Continue reading >>
Ketone Bodies: A Review Of Physiology, Pathophysiology And Application Of Monitoring To Diabetes.
Abstract Ketone bodies are produced by the liver and used peripherally as an energy source when glucose is not readily available. The two main ketone bodies are acetoacetate (AcAc) and 3-beta-hydroxybutyrate (3HB), while acetone is the third, and least abundant, ketone body. Ketones are always present in the blood and their levels increase during fasting and prolonged exercise. They are also found in the blood of neonates and pregnant women. Diabetes is the most common pathological cause of elevated blood ketones. In diabetic ketoacidosis (DKA), high levels of ketones are produced in response to low insulin levels and high levels of counterregulatory hormones. In acute DKA, the ketone body ratio (3HB:AcAc) rises from normal (1:1) to as high as 10:1. In response to insulin therapy, 3HB levels commonly decrease long before AcAc levels. The frequently employed nitroprusside test only detects AcAc in blood and urine. This test is inconvenient, does not assess the best indicator of ketone body levels (3HB), provides only a semiquantitative assessment of ketone levels and is associated with false-positive results. Recently, inexpensive quantitative tests of 3HB levels have become available for use with small blood samples (5-25 microl). These tests offer new options for monitoring and treating diabetes and other states characterized by the abnormal metabolism of ketone bodies. Continue reading >>
Ketone bodies Acetone Acetoacetic acid (R)-beta-Hydroxybutyric acid Ketone bodies are three water-soluble molecules (acetoacetate, beta-hydroxybutyrate, and their spontaneous breakdown product, acetone) that are produced by the liver from fatty acids during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, prolonged intense exercise,, alcoholism or in untreated (or inadequately treated) type 1 diabetes mellitus. These ketone bodies are readily picked up by the extra-hepatic tissues, and converted into acetyl-CoA which then enters the citric acid cycle and is oxidized in the mitochondria for energy. In the brain, ketone bodies are also used to make acetyl-CoA into long-chain fatty acids. Ketone bodies are produced by the liver under the circumstances listed above (i.e. fasting, starving, low carbohydrate diets, prolonged exercise and untreated type 1 diabetes mellitus) as a result of intense gluconeogenesis, which is the production of glucose from non-carbohydrate sources (not including fatty acids). They are therefore always released into the blood by the liver together with newly produced glucose, after the liver glycogen stores have been depleted (these glycogen stores are depleted after only 24 hours of fasting). When two acetyl-CoA molecules lose their -CoAs, (or Co-enzyme A groups) they can form a (covalent) dimer called acetoacetate. Beta-hydroxybutyrate is a reduced form of acetoacetate, in which the ketone group is converted into an alcohol (or hydroxyl) group (see illustration on the right). Both are 4-carbon molecules, that can readily be converted back into acetyl-CoA by most tissues of the body, with the notable exception of the liver. Acetone is the decarboxylated form of acetoacetate which cannot be converted Continue reading >>
Overview Structure two types acetoacetate β-hydroxybutyrate β-hydroxybutyrate + NAD+ → acetoacetate + NADH ↑ NADH:NAD+ ratio results in ↑ β-hydroxybutyrate:acetoacetate ratio 1 ketone body = 2 acetyl-CoA Function produced by the liver brain can use ketones if glucose supplies fall >1 week of fasting can provide energy to body in prolonged energy needs prolonged starvation glycogen and gluconeogenic substrates are exhausted can provide energy if citric acid cycle unable to function diabetic ketoacidosis cycle component (oxaloacetate) consumed for gluconeogenesis alcoholism ethanol dehydrogenase consumes NAD+ (converts to NADH) ↑ NADH:NAD+ ratio in liver favors use of oxaloacetate for ketogenesis rather than gluconeogenesis. RBCs cannot use ketones as they lack mitochondria Synthesis occurs in hepatocyte mitochondria liver cannot use ketones as energy lacks β-ketoacyl-CoA transferase (thiophorase) which converts acetoacetate to acetoacetyl under normal conditions acetoacetate = β-hydroxybutyrate HMG CoA synthase is rate limiting enzyme Clinical relevance ketoacidosis pathogenesis ↑ ketone levels caused by poorly controlled type I diabetes mellitus liver ketone production exceeds ketone consumption in periphery possible in type II diabetes mellitus but rare alcoholism chronic hypoglycemia results in ↑ ketone production presentation β-hydroxybutyrate > acetoacetate due to ↑ NADH:NAD+ ratio acetone gives breath a fruity odor polyuria ↑ thirst tests ↓ plasma HCO3 hypokalemia individuals are initially hyperkalemic (lack of insulin + acidosis) because K leaves the cells overall though the total body K is depleted replete K in these patients once the hyperkalemia begins to correct nitroprusside urine test for ketones may not be strongly + does not detect Continue reading >>
Ketone Bodies Formed In The Liver Are Exported To Other Organs
Ketone Bodies In human beings and most other mammals, acetyl-CoA formed in the liver during oxidation of fatty acids may enter the citric acid cycle (stage 2 of Fig. 16-7) or it may be converted to the "ketone bodies" acetoacetate, D-β-hydroxybutyrate, and acetone for export to other tissues. (The term "bodies" is a historical artifact; these compounds are soluble in blood and urine.) Acetone, produced in smaller quantities than the other ketone bodies, is exhaled. Acetoacetate and D-β-hydroxybutyrate are transported by the blood to the extrahepatic tissues, where they are oxidized via the citric acid cycle to provide much of the energy required by tissues such as skeletal and heart muscle and the renal cortex. The brain, which normally prefers glucose as a fuel, can adapt to the use of acetoacetate or D-β-hydroxybutyrate under starvation conditions, when glucose is unavailable. A major determinant of the pathway taken by acetyl-CoA in liver mitochondria is the availability of oxaloacetate to initiate entry of acetyl-CoA into the citric acid cycle. Under some circumstances (such as starvation) oxaloacetate is drawn out of the citric acid cycle for use in synthesizing glucose. When the oxaloacetate concentration is very low, little acetyl-CoA enters the cycle, and ketone body formation is favored. The production and export of ketone bodies from the liver to extrahepatic tissues allows continued oxidation of fatty acids in the liver when acetyl-CoA is not being oxidized via the citric acid cycle. Overproduction of ketone bodies can occur in conditions of severe starvation and in uncontrolled diabetes. The first step in formation of acetoacetate in the liver (Fig. 16-16) is the enzymatic condensation of two molecules of acetyl-CoA, catalyzed by thiolase; this is simply Continue reading >>
What Are Ketones?
What are ketones and what causes them? Ketones are the result of the body burning fat for energy or fuel. For a person with diabetes, ketones are often the result of prolonged high blood sugar and insulin deficiency. Without the right amount of insulin, glucose starts to build up in the blood stream and doesn't enter the cells. The cells burn fat instead of glucose, and ketones form in the blood and spill into the urine. Some causes of high blood sugar are: Missing an insulin dose or skipping some oral medications. A disconnected or blocked insulin pump tube. Being sick with the flu. High levels of stress. Eating more carbohydrates than your medication covers. What are the signs that I should test for ketones? Symptoms of high blood sugar include frequent urination, frequent thirst, blurry vision, dry mouth, vomiting, and fatigue. There are several scenarios that should prompt a test for ketones. If your blood sugar is over 240 mg/dl for two tests in a row. When you are ill. When your blood sugar is over 240 mg/dl and you are planning on exercising. If you are pregnant, you should test for ketones each morning before breakfast and whenever blood sugars are elevated. How do I test for ketones? There are two ways to test for ketones - by testing your urine or your blood. Ketones appear first in the blood stream and are later present in the urine, so testing your blood for ketones is the best way to check for an early problem. To check urine for ketones, you must collect a urine sample or dip a ketone test strip into a fresh stream of urine. After waiting for the time suggested by the ketone strip manufacturer, you compare the color strip to the chart on the bottle. The darker the color, the higher the amount of ketones in the urine. At this time, there are just a few mete Continue reading >>
Sort Ketone Bodies -->Represent 3 molecules that are formed when excess acetyl CoA cannot enter the TCA Cycle -->Represents 3 major molecules: 1)Acetoacetate 2)β-Hydroxybutyrate 3)Acetone -->Normal people produces ketones at a low rate -->Are only formed in the **LIVER**(by liver mitochondria) Reactions that lead to the formation of ketone bodies (***See pwrpt***) 1)2 Acetyl CoA molecules condense to form ***Acetoacetyl-CoA -->Is catalyzed by THIOLASE -->Represent the oppostie of thiolysis step in the oxidation of fatty acids -->Represent the parent compound of the 3 ketone bodies (2)Acetoacetyl CoA then reacts with another mol. of acetyl CoA to form **HMG-CoA* (3-hydroxy-3-methylglutaryl CoA) & *CoA** -->Reaction is catalyzed by **HMG-CoA Synthetase** -->HMG-CoA has 2 fates (can either progress to form ketone bodies OR can enter the pathway of CHOLESTEROL synthesis) -->Represent the **RATE-LIMITING STEP** in the synthesis of ketone bodies (3)HMG-CoA is cleaved to form **Acetoacetate**(First major ketone; represent ~20% of ketones) & another mol. of acetyl CoA -->Catalyzed by **HMG-CoA Lyase** (4) Acetoacetae can lead to the formation of β-hydroxybutyrate (~78% of ketone bodies) & Acetone (~2% of ketone bodies) via 2 separte reactions Interrelationships of the ketone bodies from Acetoacetate (1)Formation of β-hydroxybutyrate -->Acetoacetate will be reduced to form β-hyroxybutyrate in the mitochondrial matrix of the liver cell -->Is a REVERSIBLE RXN. -->Requires 1 mol of NADH (***Dependent on the NADH/NAD ratio inside the mitochondria) -->Catalyzed by β-hydroxybutyrate dehydrogenase (2)Formation of Acetone -->A slower, **spontaneous** decarboxylation to acetone -->In **DIABETIC KETOACIDOSIS, acetone imparts a characteristic smell to the patient's breath Features of Continue reading >>