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Why Ketone Bodies Are Formed?

Diabetes And Ketones

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 >>

Utilization Of Ketone Bodies, Regulation And Clinical Significance Of Ketogenesis

Utilization Of Ketone Bodies, Regulation And Clinical Significance Of Ketogenesis

Ketone bodies are utilized by extra hepatic tissues via a series of cytosolic reactions that are essentially a reversal of ketone body synthesis; the ketones must be reconverted to acetyl Co A in the mitochondria (figure-1) Steps 1) Utilization of β-Hydroxy Butyrate Beta-hydroxybutyrate is first oxidized to acetoacetate with the production of one NADH (Figure-1, step-1). In tissues actively utilizing ketones for energy production, NAD+/NADH ratio is always higher so as to drive the β-hydroxybutyrate dehydrogenase catalyzed reaction in the direction of acetoacetate synthesis. Biological significance D (-)-3-Hydroxybutyrate is oxidized to produce acetoacetate as well as NADH for use in oxidative phosphorylation. D (-)-3-Hydroxybutyrate is the main ketone body excreted in urine. 2) Utilization of Acetoacetate a) Coenzyme A must be added to the acetoacetate. The thioester bond is a high energy bond, so ATP equivalents must be used. In this case the energy comes from a trans esterification of the CoASH from succinyl CoA to acetoacetate by Coenzyme A transferase (Figure-1, step-2), also called Succinyl co A: Acetoacetate co A transferase, also known as Thiophorase. The Succinyl CoA comes from the TCA cycle. This reaction bypasses the Succinyl-CoA synthetase step of the TCA cycle; hence there is no GTP formation at this step although it does not alter the amount of carbon in the cycle. Biological significance The liver has acetoacetate available to supply to other organs because it lacks this particular CoA transferase and that is the reason “Ketone bodies are synthesized in the liver but utilized in the peripheral tissues”. The latter enzyme is present at high levels in most tissues except the liver. Importantly, very low-level of enzyme expression in the liver allows t Continue reading >>

Ketone Bodies

Ketone Bodies

The term “ketone bodies” refers primarily to two compounds: acetoacetate and β‐hydroxy‐butyrate, which are formed from acetyl‐CoA when the supply of TCA‐cycle intermediates is low, such as in periods of prolonged fasting. They can substitute for glucose in skeletal muscle, and, to some extent, in the brain. The first step in ketone body formation is the condensation of two molecules of acetyl‐CoA in a reverse of the thiolase reaction. The product, acetoacetyl‐CoA, accepts another acetyl group from acetyl‐CoA to form β‐hydroxy‐β‐hydroxymethylglutaryl‐CoA (HMG‐CoA). HMG‐CoA has several purposes: It serves as the initial compound for cholesterol synthesis or it can be cleaved to acetoacetate and acetyl‐CoA. Acetoacetate can be reduced to β‐hydroxybutyrate or can be exported directly to the bloodstream. Acetoacetate and β‐hydroxybutyrate circulate in the blood to provide energy to the tissues. Acetoacetate can also spontaneously decarboxylate to form acetone: Although acetone is a very minor product of normal metabolism, diabetics whose disease is not well‐managed often have high levels of ketone bodies in their circulation. The acetone that is formed from decarboxylation of acetoacetate is excreted through the lungs, causing characteristic “acetone breath.” Continue reading >>

Ketones

Ketones

Excess ketones are dangerous for someone with diabetes... Low insulin, combined with relatively normal glucagon and epinephrine levels, causes fat to be released from fat cells, which then turns into ketones. Excess formation of ketones is dangerous and is a medical emergency In a person without diabetes, ketone production is the body’s normal adaptation to starvation. Blood sugar levels never get too high, because the production is regulated by just the right balance of insulin, glucagon and other hormones. However, in an individual with diabetes, dangerous and life-threatening levels of ketones can develop. What are ketones and why do I need to know about them? Ketones and ketoacids are alternative fuels for the body that are made when glucose is in short supply. They are made in the liver from the breakdown of fats. Ketones are formed when there is not enough sugar or glucose to supply the body’s fuel needs. This occurs overnight, and during dieting or fasting. During these periods, insulin levels are low, but glucagon and epinephrine levels are relatively normal. This combination of low insulin, and relatively normal glucagon and epinephrine levels causes fat to be released from the fat cells. The fats travel through the blood circulation to reach the liver where they are processed into ketone units. The ketone units then circulate back into the blood stream and are picked up by the muscle and other tissues to fuel your body’s metabolism. In a person without diabetes, ketone production is the body’s normal adaptation to starvation. Blood sugar levels never get too high, because the production is regulated by just the right balance of insulin, glucagon and other hormones. However, in an individual with diabetes, dangerous and life-threatening levels of ketone Continue reading >>

Ketone Body

Ketone Body

ketone body n. Any of three compounds, acetoacetic acid, acetone, and beta-hydroxybutyric acid, that are ketones or derivatives of ketones and are intermediate products of fatty acid metabolism. Ketone bodies accumulate in the blood and urine when fats are being used for energy instead of carbohydrates, as in individuals affected by starvation or uncontrolled diabetes mellitus. Also called acetone body. American Heritage® Dictionary of the English Language, Fifth Edition. Copyright © 2016 by Houghton Mifflin Harcourt Publishing Company. Published by Houghton Mifflin Harcourt Publishing Company. All rights reserved. ketone body n (Biochemistry) biochem any of three compounds (acetoacetic acid, 3-hydroxybutanoic acid, and acetone) produced when fatty acids are broken down in the liver to provide a source of energy. Excess ketone bodies are present in the blood and urine of people unable to use glucose as an energy source, as in diabetes and starvation. Also called: acetone body Collins English Dictionary – Complete and Unabridged, 12th Edition 2014 © HarperCollins Publishers 1991, 1994, 1998, 2000, 2003, 2006, 2007, 2009, 2011, 2014 ke′tone bod′y n. any of several compounds, as acetoacetic acid, acetone, and hydroxybutyric acid, that are intermediate in the metabolism of fatty acids and are produced in excessive amounts under certain abnormal conditions, as in diabetes mellitus. Random House Kernerman Webster's College Dictionary, © 2010 K Dictionaries Ltd. Copyright 2005, 1997, 1991 by Random House, Inc. All rights reserved. Noun 1. ketone body - a ketone that is an intermediate product of the breakdown of fats in the body; any of three compounds (acetoacetic acid, acetone, and/or beta-hydroxybutyric acid) found in excess in blood and urine of persons with meta Continue reading >>

Ketone Bodies Mimic The Life Span Extending Properties Of Caloric Restriction

Ketone Bodies Mimic The Life Span Extending Properties Of Caloric Restriction

The extension of life span by caloric restriction has been studied across species from yeast and Caenorhabditis elegans to primates. No generally accepted theory has been proposed to explain these observations. Here, we propose that the life span extension produced by caloric restriction can be duplicated by the metabolic changes induced by ketosis. From nematodes to mice, extension of life span results from decreased signaling through the insulin/insulin-like growth factor receptor signaling (IIS) pathway. Decreased IIS diminishes phosphatidylinositol (3,4,5) triphosphate (PIP3) production, leading to reduced PI3K and AKT kinase activity and decreased forkhead box O transcription factor (FOXO) phosphorylation, allowing FOXO proteins to remain in the nucleus. In the nucleus, FOXO proteins increase the transcription of genes encoding antioxidant enzymes, including superoxide dismutase 2, catalase, glutathione peroxidase, and hundreds of other genes. An effective method for combating free radical damage occurs through the metabolism of ketone bodies, ketosis being the characteristic physiological change brought about by caloric restriction from fruit flies to primates. A dietary ketone ester also decreases circulating glucose and insulin leading to decreased IIS. The ketone body, d-β-hydroxybutyrate (d-βHB), is a natural inhibitor of class I and IIa histone deacetylases that repress transcription of the FOXO3a gene. Therefore, ketosis results in transcription of the enzymes of the antioxidant pathways. In addition, the metabolism of ketone bodies results in a more negative redox potential of the NADP antioxidant system, which is a terminal destructor of oxygen free radicals. Addition of d-βHB to cultures of C. elegans extends life span. We hypothesize that increasing t Continue reading >>

Ketosis, Ketone Bodies, And Ketoacidosis – An Excerpt From Modern Nutritional Diseases, 2nd Edition

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 >>

Urine Tests For Diabetes: Glucose Levels And Ketones

Urine Tests For Diabetes: Glucose Levels And Ketones

The human body primarily runs on glucose. When your body is low on glucose, or if you have diabetes and don’t have enough insulin to help your cells absorb the glucose, your body starts breaking down fats for energy. Ketones (chemically known as ketone bodies) are byproducts of the breakdown of fatty acids. The breakdown of fat for fuel and the creation of ketones is a normal process for everyone. In a person without diabetes, insulin, glucagon, and other hormones prevent ketone levels in the blood from getting too high. However, people with diabetes are at risk for ketone buildup in their blood. If left untreated, people with type 1 diabetes are at risk for developing a condition called diabetic ketoacidosis (DKA). While rare, it’s possible for people with type 2 diabetes to experience DKA in certain circumstances as well. If you have diabetes, you need to be especially aware of the symptoms that having too many ketones in your body can cause. These include: If you don’t get treatment, the symptoms can progress to: a fruity breath odor stomach pain trouble breathing You should always seek immediate medical attention if your ketone levels are high. Testing your blood or urine to measure your ketone levels can all be done at home. At-home testing kits are available for both types of tests, although urine testing continues to be more common. Urine tests are available without a prescription at most drugstores, or you can buy them online. You should test your urine or blood for ketones when any of the following occurs: Your blood sugar is higher than 240 mg/dL. You feel sick or nauseated, regardless of your blood sugar reading. To perform a urine test, you urinate into a clean container and dip the test strip into the urine. For a child who isn’t potty-trained, a pa Continue reading >>

Triacylglycerol Metabolism

Triacylglycerol Metabolism

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 >>

Urine - For Ketone, Ketone Bodies (ketonuria)

Urine - For Ketone, Ketone Bodies (ketonuria)

Sample The is done on the urine. Indication It is advised in diabetic patients for the early diagnosis of ketoacidosis. To evaluate the diabetic patient in a coma. Definition Increased ketone bodies in blood are called Ketonemia. Increased excretion in the urine is called Ketonuria. Pathophysiology Ketone bodies are seen in case of decreased availability of carbohydrates like starvation or frequent vomiting. Another possibility is decreased utilization of carbohydrates like diabetes mellitus, and glycogen storage disease. High fat and low carbohydrates diet are ketogenic and increase ketone bodies in the blood. Ketones are the end product of fatty acid catabolism. Ketones are formed when the glucose as a source of energy is not present. This situation happens when there is no insulin so glucose cannot enter the cells. In that case, ketone bodies are the source of energy for the body, particularly to the brain. In case of fasting for 3 to 4 days, then 30 to 40% body energy is provided by the ketone bodies. Ketones bodies are the end product of fatty acid breakdown and consists of : Beta-hydroxybutyric acid. Acetoacetic acid. Acetone. The β- hydroxybutyric acid + acetoacetic acid readily converts to acetone. In the blood: Acetone is the minor amount. Acetoacetate and β- hydroxybutyrate are equal in amount and are the main ketone bodies. in a healthy person, ketones are formed in the liver but there is a negligible amount in urine. The outcome of Increased Ketones in the blood leads to : Electrolyte imbalance. Dehydration. If not corrected then leads to acidosis coma and ultimately death. Ketones are present in the urine when a threshold level of ketones exceed the normal level in the blood. Normal In Urine Ketone bodies are negative. Small amount = < 20 mg/dL. Moderate Continue reading >>

Ketone Body Metabolism

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 >>

Ketone Bodies Metabolism

Ketone Bodies Metabolism

1. Metabolism of ketone bodies Gandham.Rajeev Email:[email protected] 2. • Carbohydrates are essential for the metabolism of fat or FAT is burned under the fire of carbohydrates. • Acetyl CoA formed from fatty acids can enter & get oxidized in TCA cycle only when carbohydrates are available. • During starvation & diabetes mellitus, acetyl CoA takes the alternate route of formation of ketone bodies. 3. • Acetone, acetoacetate & β-hydroxybutyrate (or 3-hydroxybutyrate) are known as ketone bodies • β-hydroxybutyrate does not possess a keto (C=O) group. • Acetone & acetoacetate are true ketone bodies. • Ketone bodies are water-soluble & energy yielding. • Acetone, it cannot be metabolized 4. CH3 – C – CH3 O Acetone CH3 – C – CH2 – COO- O Acetoacetate CH3 – CH – CH2 – COO- OH I β-Hydroxybutyrate 5. • Acetoacetate is the primary ketone body. • β-hydroxybutyrate & acetone are secondary ketone bodies. • Site: • Synthesized exclusively by the liver mitochondria. • The enzymes are located in mitochondrial matrix. • Precursor: • Acetyl CoA, formed by oxidation of fatty acids, pyruvate or some amino acids 6. • Ketone body biosynthesis occurs in 5 steps as follows. 1. Condensation: • Two molecules of acetyl CoA are condensed to form acetoacetyl CoA. • This reaction is catalyzed by thiolase, an enzyme involved in the final step of β- oxidation. 7. • Acetoacetate synthesis is appropriately regarded as the reversal of thiolase reaction of fatty acid oxidation. 2. Production of HMG CoA: • Acetoacetyl CoA combines with another molecule of acetyl CoA to produce β-hydroxy β-methyl glutaryl CoA (HMC CoA). • This reaction is catalyzed by the enzyme HMG CoA synthase. 8. • Mitochondrial HMG CoA is used for ketogenesis. Continue reading >>

Ketone Bodies

Ketone Bodies

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 >>

Ketones

Ketones

Ketones are a beneficial product of fat metabolism in the body. When carbohydrate intake is restricted, it lowers blood sugar and insulin levels. As insulin levels fall and energy is needed, fatty acids flow from the fat cells into the bloodstream and are taken up by various cells and metabolized in a process called beta-oxidation. The end result of beta-oxidation is a molecule called acetyl-coA, and as more fatty acids are released and metabolized, acetyl-coA levels in the cells rise. This causes a sort of metabolic “feedback loop” which triggers liver cells to shunt excess acetyl-Coa into ketogenesis, or the making of ketone bodies. Once created, the liver dumps the ketone bodies into the blood stream and they are taken up by skeletal and heart muscle cells at rates of availability. In addition, the brain begins to use ketones as an alternate fuel when blood levels are high enough to cross the blood brain barrier. Testing Laboratory Microbiology - Air Quality - Mold Asbestos - Environmental - Lead emsl.com There are three major types of ketone bodies present in the human blood stream when the metabolic process of ketosis is dominant: Acetoacetate (AcAc) is created first β-hydroxybutyrate (BHB) is created from acetoacetate Acetone is a spontaneously created side product of acetoacetate In times of starvation, or a low carbohydrate intake resulting in low insulin levels, ketone bodies supply up to 50% of the energy requirements for most body tissues, and up to 70% of the energy required by the brain. Glucose is the main source of fuel for neurons when the diet is high in carbohydrates. But when carbs are restricted, ketogenesis becomes the primary fuel process for most cells. During fasting or low carbohydrate intake, levels of ketone bodies in the blood stream can Continue reading >>

Ketone Ester Effects On Metabolism And Transcription

Ketone Ester Effects On Metabolism And Transcription

Abstract Ketosis induced by starvation or feeding a ketogenic diet has widespread and often contradictory effects due to the simultaneous elevation of both ketone bodies and free fatty acids. The elevation of ketone bodies increases the energy of ATP hydrolysis by reducing the mitochondrial NAD couple and oxidizing the coenzyme Q couple, thus increasing the redox span between site I and site II. In contrast, metabolism of fatty acids leads to a reduction of both mitochondrial NAD and mitochondrial coenzyme Q causing a decrease in the ΔG of ATP hydrolysis. In contrast, feeding ketone body esters leads to pure ketosis, unaccompanied by elevation of free fatty acids, producing a physiological state not previously seen in nature. The effects of pure ketosis on transcription and upon certain neurodegenerative diseases make approach not only interesting, but of potential therapeutic value. PRODUCTION OF KETONE BODIES Ketone bodies are formed in the liver from free fatty acids released from adipose tissue. As the blood concentration of free fatty acids increases, concentration of blood ketone bodies is correspondingly increased (1, 2). Ketone bodies serve as a physiological respiratory substrate and are the physiological response to prolonged starvation in man (3, 4), where the blood level of ketones reaches 5–7 mM (5). If the release of free fatty acids from adipose tissue exceeds the capacity of tissue to metabolize them, as occurs during insulin deficiency of type I diabetes or less commonly in the insulin resistance of type II diabetes, severe and potentially fatal diabetic ketoacidosis can occur, where blood ketone body levels can reach 20 mM or higher (2) resulting in a decrease in blood bicarbonate to almost 0 mM and blood pH to 6.9. Diabetic ketoacidosis, which is a Continue reading >>

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