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How Are Ketones Formed In The Body

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 >>

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 >>

Ketone Body Formation

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 >>

Ketone Bodies Formed In The Liver Are Exported To Other Organs

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 >>

Ketone Bodies: A Review Of Physiology, Pathophysiology And Application Of Monitoring To Diabetes.

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 >>

Introduction To Degradation Of Lipids And Ketone Bodies Metabolism

Introduction To Degradation Of Lipids And Ketone Bodies Metabolism

Content: 1. Introduction to degradation of lipids and ketone bodies metabolism 2. Lipids as source of energy – degradation of TAG in cells, β-oxidation of fatty acids 3. Synthesis and utilisation of ketone bodies _ Triacylglycerol (TAG) contain huge amounts of chemical energy. It is very profitable to store energy in TAG because 1 g of water-free TAG stores 5 times more energy than 1 g of hydrated glycogen. Complete oxidation of 1 g of TAG yields 38 kJ, 1g of saccharides or proteins only 17 kJ. Man that weighs 70 kg has 400 000 kJ in his TAG (that weight approximately 10,5 kg). This reserve of energy makes us able to survive starving in weeks. TAG accumulate predominantly in adipocyte cytoplasm. There are more types of fatty acid oxidation. Individual types can be distinguished by different Greek letters. Greek letter denote atom in the fatty acid chain where reactions take place. β-oxidation is of major importance, it is localised in mitochondrial matrix. ω- and α- oxidation are localised in endoplasmic reticulum. Animal cells cannot convert fatty acids to glucose. Gluconeogenesis requires besides other things (1) energy, (2) carbon residues. Fatty acids are rich source of energy but they are not source of carbon residues (there is however one important exception, i.e. odd-numbered fatty acids). This is because cells are not able to convert AcCoA to neither pyruvate, nor OAA. Both carbons are split away as CO2. PDH is irreversible. Plant cells are capable of conversion of AcCoA to OAA in glyoxylate cycle. _ Lipids as source of energy – degradation of TAG in cells, β-oxidation of fatty acids Lipids are used for energy production, this process take place in 3 phases: 1) Lipid mobilisation – hydrolysis of TAG to FA and glycerol. FA and glycerol are transported Continue reading >>

Ketone Bodies Metabolic Pathway (pw:0000069)

Ketone Bodies Metabolic Pathway (pw:0000069)

Description The ketone bodies metabolic pathway is used to convert acetyl-CoA formed in the liver into "ketone bodies": acetone, and more importantly acetoacetate and 3-hydroxybutyrate, which are transported in the blood to extrahepatic tissues where they are converted to acetyl-CoA and oxidized via the citrate cycle pathway for energy. The brain, which usually uses glucose for energy, can utilize ketone bodies under starvation conditions, when glucose is not available. When acetyl-CoA is not being metaboli...(more) Description: ENCODES a protein that exhibits 3-hydroxybutyrate dehydrogenase activity (ortholog); NAD binding (ortholog); oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor (ortholog); INVOLVED IN epithelial cell differentiation (ortholog); fatty acid beta-oxidation (ortholog); heme metabolic process (ortholog); PARTICIPATES IN butanoate metabolic pathway; ketone bodies metabolic pathway; FOUND IN cytoplasm (ortholog); cytosol (ortholog); extracellular exosome (ortholog); INTERACTS WITH 2,3,7,8-tetrachlorodibenzodioxine; 2,4-dinitrotoluene; 2,6-dinitrotoluene 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 >>

Ketosis

Ketosis

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 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

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 >>

What Are Ketones?

What Are Ketones?

With the gradual resurgence of low-carb diets in recent years, the word “ketones” is thrown around a lot. But many people aren’t really aware of the details. What are ketones, really? And what do they do in the body? There can be a lot of misinformation regarding the answers to these questions, so read on for a full overview of ketones and their role in a ketogenic diet. Ketones, also known as “ketone bodies,” are byproducts of the body breaking down fat for energy that occurs when carbohydrate intake is low. Here’s how it works: When there isn’t a sufficient level of available glucose — which is what the body uses for its main source of fuel — and glycogen levels are depleted, blood sugar and insulin are lowered and the body looks for an alternative source of fuel: in this case, fat. This process can happen when a person fasting, after prolonged exercise, during starvation, or when eating a low-carb, ketogenic diet. And when the body begins breaking down fats for energy like this, a process known as beta-oxidation, ketones are formed for use as fuel for the body and brain. This is known as ketosis. People following a ketogenic diet specifically reduce their carbohydrate intake for this reason: to create ketones for energy. Many people use the benefits of ketosis — less reliance on carbs and more burning of fat — to possibly help lower blood pressure, reduce cravings, improve cholesterol, increase weight loss, improve energy, and more. TYPES OF KETONE BODIES So, what else about ketones do we need to know? To start, there are technically three types of ketone bodies: Acetoacetate (AcAc) Beta-hydroxybutyric acid (BHB) Acetone Both acetoacetate and beta-hydroxybutyrate are responsible for transporting energy from the liver to other tissues in the body Continue reading >>

Ketone Bodies

Ketone Bodies

Also found in: Dictionary, Thesaurus, Legal, Financial, Encyclopedia, Wikipedia. Related to ketone bodies: ketosis ketone [ke´tōn] any compound containing the carbonyl group, C=O, and having hydrocarbon groups attached to the carbonyl carbon, i.e., the carbonyl group is within a chain of carbon atoms. ketone bodies the substances acetone, acetoacetic acid, and β-hydroxybutyric acid; except for acetone (which may arise spontaneously from acetoacetic acid), they are normal metabolic products of lipid and pyruvate within the liver, and are oxidized by muscles. Excessive production leads to urinary excretion of these bodies, as in diabetes mellitus; see also ketosis. Called also acetone bodies. Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. © 2003 by Saunders, an imprint of Elsevier, Inc. All rights reserved. ketone bodies two products of lipid pyruvate metabolism, beta-hydroxybutyric acid and aminoacetic acid, from which acetone may arise spontaneously. Ketone bodies are produced from acetyl-CoA in the liver and are oxidized by the muscles. Excessive production leads to their excretion in urine, as in diabetes mellitus. Also called acetone bodies. Ketones, Blood and Urine Synonym/acronym: Ketone bodies, acetoacetate, acetone. Common use To investigate diabetes as the cause of ketoacidosis and monitor therapeutic interventions. Specimen Serum (1 mL) collected from gold-, red-, or red/gray-top tube. Urine (5 mL), random or timed specimen, collected in a clean plastic collection container. Normal findings (Method: Colorimetric nitroprusside reaction) Negative. Description Ketone bodies refer to the three intermediate products of metabolism: acetone, acetoacetic acid, and β-hydroxybutyrate. Even though β-hydroxybutyrate 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 >>

What Are Ketone Bodies And Why Are They In The Body?

What Are Ketone Bodies And Why Are They In The Body?

If you eat a calorie-restricted diet for several days, you will increase the breakdown of your fat stores. However, many of your tissues cannot convert these fatty acid products directly into ATP, or cellular energy. In addition, glucose is in limited supply and must be reserved for red blood cells -- which can only use glucose for energy -- and brain tissues, which prefer to use glucose. Therefore, your liver converts many of these fatty acids into ketone bodies, which circulate in the blood and provide a fuel source for your muscles, kidneys and brain. Video of the Day Low fuel levels in your body, such as during an overnight fast or while you are dieting, cause hormones to increase the breakdown of fatty acids from your stored fat tissue. These fatty acids travel to the liver, where enzymes break the fatty acids into ketone bodies. The ketone bodies are released into the bloodstream, where they travel to tissues that have the enzymes to metabolize ketone bodies, such as your muscle, brain, kidney and intestinal cells. The breakdown product of ketone bodies goes through a series of steps to form ATP. Conditions of Ketone Body Utilization Your liver will synthesize more ketone bodies for fuel whenever your blood fatty acid levels are elevated. This will happen in response to situations that promote low blood glucose, such as an overnight fast, prolonged calorie deficit, a high-fat and low-carbohydrate diet, or during prolonged low-intensity exercise. If you eat regular meals and do not typically engage in extremely long exercise sessions, the level of ketone bodies in your blood will be highest after an overnight fast. This level will drop when you eat breakfast and will remain low as long as you eat regular meals with moderate to high carbohydrate content. Ketone Bodi Continue reading >>

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