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How Ketones Are Formed?

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 >>

Understanding Ketosis

Understanding Ketosis

To gain a better understanding of ketosis and the ketogenic diet, it is important to take a look at the physiology behind the diet. If you recall from the article What is a Ketogenic Diet? the goal of a ketogenic diet is to induce ketosis by increasing ketone body production. A key step in understanding the diet is to learn what ketosis is, what are ketones and what do they do. “Normal” Metabolism Learning the basics of the various metabolic processes of the body will better your ability to understand ketosis. Under the normal physiological conditions that are common today, glucose is our body’s primary source of energy. Following ingestion, carbohydrates are broken down into glucose and released into the blood stream. This results in the release of insulin from the pancreas. Insulin not only inhibits fat oxidation but also acts as a key holder for cells by allowing glucose from the blood to be shuttled into cells via glucose transporters (GLUT). The amount of insulin required for this action varies between individuals depending on their insulin sensitivity. Once inside the cell, glucose undergoes glycolysis, a metabolic process that produces pyruvate and energy in the form of adenosine triphosphate (ATP). Once pyruvate is formed as an end product of glycolysis, it is shuttled into the mitochondria, where it is converted to acetyl-CoA by pyruvate dehydrogenase. Acetyl-CoA then enters the TCA cycle to produce additional energy with the aid of the electron transport chain. Since glucose is so rapidly metabolized for energy production and has a limited storage capacity, other energy substrates, such as fat, get stored as triglycerides due to our body’s virtually infinite fat storage capacity. When a sufficient source of carbohydrates is not available, the body adap 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 >>

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 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 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

Ketone Bodies

Introductory discusion of fat metabolism, exercise, and fasting. Fatty acids can be used as the major fuel for tissues such as muscle, but they cannot cross the blood-brain barrier, and thus cannot be used by the central nervous system (CNS). This becomes a major problem during starvation (fasting), particularly for organisms such as ourselves in which CNS metabolism constitute a major portion of the resting basal metabolic rate. These organism must provide glucose to the CNS to provide for metabolic needs, and thus during the initial fasting period must break down substantial amounts of muscle tissue (protein) to provide the amino acid precursors of gluconeogenesis. Obviously the organism could not survive long under such a regime. What is needed is an alternate fuel source based on fat rather than muscle. The so-called ketone bodies serve this function: Note that only two of the ketone bodies are in fact ketones, and that acetone is an "unintentional" breakdown product resulting from the instability of acetoacetate at body temperature. Acetone is not available as fuel to any significant extent, and is thus a waste product. CNS tissues can use ketone bodies any time, the problem is the normally very low concentrations (< 0.3 mM) compared to glucose (about 4 mM). Since the KM's for both are similar, the CNS doesn't begin to use ketone bodies in preference to glucose until their concentration exceed's the concentration of glucose in the serum. The system becomes saturated at about 7 mM. The limiting factor in using ketone bodies then becomes the ability of the liver to synthesis them, which requires the induction of the enzymes required for acetoacetate biosynthesis. Normal glucose concentrations inhibit ketone body synthesis, thus the ketone bodies will only begin to be 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 >>

What Are Ketones?

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 >>

Ketone Bodies As A Fuel For The Brain During Starvation

Ketone Bodies As A Fuel For The Brain During Starvation

THE STATUS OF OUR KNOWLEDGE OF STARVATION AND BRAIN METABOLISM IN HUMANS WHEN I BEGAN MY RESEARCH This story begins in the early 1960s when the general level of knowledge about whole-body metabolism during human starvation was grossly deficient. This was partly caused by a lack of accurate and specific methods for measuring hormones and fuels in biological fluids, which became available about 1965.11 Rigidly designed protocols for studying human volunteers or obese patients, who underwent semi- or total starvation for prolonged periods of time, were not widely employed, and much of the published data regarding metabolic events during starvation were not readily accessible. To complicate matters further, a great deal of the available data was confusing because much of the supposition regarding mechanisms used by the body to survive prolonged periods of starvation was based upon information that was obtained from nonstandardized and often erroneous procedures for studying metabolism. For example, the rate of urinary nitrogen excretion during starvation was sometimes confounded by the consumption of carbohydrate during the studies. Today, students of biochemistry take for granted the fact that tissues of the human body have a hierarchy of fuel usage. They know that the brain, an organ devoted to using glucose, can switch to use ketone bodies during prolonged starvation (2–3 days), thus sparing glucose for other tissues (i.e. red blood cells must use glucose as a fuel; without mitochondria, they have no choice!). However, this fundamental insight into human metabolism was not recognized in the early 1960s, when my research in this area began. How this simple but fundamental fact that ketone bodies provide critical fuels for the brain was discovered and its implication for Continue reading >>

Ketone Bodies

Ketone Bodies

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[1] during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, prolonged intense exercise,[2], 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.[3] 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).[1] 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)[1]. 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 >>

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 >>

Enolate Formation From Ketones

Enolate Formation From Ketones

Voiceover: In order to see how to form enolate anions, and in this video we're just gonna look in more detail how to form enolate anions from ketones. And so the ketone we have here is acetone. To find our alpha carbon, we just look at the carbon next to our carbonyl carbon, so this could be an alpha carbon, and this could be an alpha carbon. Each one of those alpha carbons has three alpha protons, and so there's a total of six. I'm just gonna draw one in here, and this is the one that we're going to show being deprotonated here. So, the base that's going to deprotonate acetone, we're gonna use LDA, which is Lithium Diisopropyl Amide And, I could go ahead and draw in the Lithium here, so Li Plus, and then we see the two isopropyl groups like that, a negative one charge on our nitrogen. So this is a very strong base, it's also very bulky and sterically hindered. So you can think about a lone pair of electrons in the nitrogen, taking that proton, leaving these electrons behind on this carbon, so we can go ahead and draw the conjugate base here. We would have electrons on this carbon now, that's a carbanion, so let me go ahead and show those electrons, these electrons in here magenta, are gonna come off onto this carbon. And this carbon is a [carbanae] because remember there's also two other hydrogens attached to it. So that's what gives it a negative one formal charge here. We can draw our resonance structure, we can show these electrons in magenta moving in here, these electrons coming off onto our oxygen, so for our resonance structure we would show the negative charge is now on our oxygen, this would be a negative one formal charge like that now. So the electrons in magenta moved into here to form our double bond, and then we can show the electrons in here in the blue Continue reading >>

Ketone Bodies: Formation And Utilisation | Living Organisms | Biology

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 >>

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 >>

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