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How Are Ketones Excreted From The Body

What Are Ketones And Are They Healthy?

What Are Ketones And Are They Healthy?

What Are Ketones and Are They Healthy? If you are up on your health news or follow anyone in the health field, you have likely heard the term ketogenic diet. The goal of the ketogenic diet is to adapt the body to utilize fat as its primary fuel source instead of sugar. The body does this by first converting fat into what are called ketones that the cells can then burn as fuel. It is at this point that I typically get asked, what are ketones? In this article, I am going to clear up any gaps, explain exactly how ketogenisis works, and why it can be so beneficial for the human body. Biological Role of Ketones For our ancestors, eating three meals a day just wasn’t a thing. Instead they would hunt and forage for the foods they could find. When there wasn’t food, they wouldn’t eat. What this means is that sometimes they would go for days at a time with no food. To sustain life during times of scarcity, the body is thought to have developed the ability to utilize fat as an alternative fuel source. In a traditional nutrition course, you would learn that sugar is the body’s primary fuel source while fat is a secondary fuel source. When sugar stores are burned up, the cells then convert to burning fat as an energy source. What we are finding out now is that fat can actually be a healthier and more sustainable source of energy. Our Society Is Full of Sugar Burners Modern day, we have an abundance of food that is available to us at all times. Most of us regularly eat three meals a day with intermittent snacking in between. This kind of frequent eating, along with an overemphasis on carb-rich and sugary foods, causes a reduced ability to burn fat. As these foods damage our bodies on a metabolic level, we actually lose the ability to produce ketones. This type of reliance on 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 >>

Ketone Bodies

Ketone Bodies

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 back into acetyl-CoA except via detoxification in the liver where it 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 >>

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 >>

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 >>

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 Bodies Vijay Patel

Ketone Bodies Vijay Patel

What are Ketone bodies? How are they formed? What are there uses? What is Ketogenic diet? Toxicity. E.g. Ketosis and Ketoacidosis etc.. Ketone bodies test. Written assignment. Overview Ketone bodies are three water soluble organic molecules acetone, acetoacetic acid, and β-hydroxybutyric acid, produced by liver from fatty acids during low availability of glucose for energy. What are ketone bodies ? How are ketone bodies formed? Fatty acid metabolism- - When carbohydrates are scarce, fatty acids are broken down to acetone, acetoacetic acid, and β-hydroxybutyric acid. - Acetone is produced from acetoacetic acid on spontaneous decarboxylation. Mostly excreted in urine or expelled in a breathe giving fruity or nail polish like smell. Uses of Ketone bodies Brain fuel: Acetoacetic acid and β-hydroxybutyric acid. (Up to 60 to 70% brain fuel) Anti-oxidative and anti-inflammatory effects. Possible drug like action: Direct injection of ACA and acetone into animal models of epilepsy prevented seizures. Nutritional Ketosis for weight loss: Daily restriction of carbohydrate to below 60 grams per day. (Mild ketosis ïƒ 1 mM, prolonged fasting ketosis ïƒ 8 to 10 mM) Ketogenic diets enhances energy levels, mental clarity, and decreases hunger. Ketone bodies have shown to improve memory in patients at risk for Alzheimer’s disease, stabilize mood in type II bipolar disorder, reduce symptoms in Parkinson’s disease. Ketogenic Diet The Atkins diet is by far the most famous ketogenic diet. The diet was developed by the late Robert C. Atkins, M.D. in the late 1980s Ketosis: Rate of synthesis > rate of utilization and blood concentration of ketone bodies increased leading to ketonemia followed by excretion in urine leading to ketonauria. Overall condition is known as 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 >>

Reference Range

Reference Range

Acetoacetate, beta-hydroxybutyrate, and acetone are ketone bodies. In carbohydrate-deficient states, fatty-acid metabolism spurs acetoacetate accumulation. The reduction of acetoacetate in the mitochondria results in beta-hydroxybutyrate production. Beta-hydroxybutyrate and acetoacetate, the predominant ketone bodies, are rich in energy. Beta-hydroxybutyrate and acetoacetate transport energy from the liver to other tissues. Acetone forms from the spontaneous decarboxylation of acetoacetate. Acetone is the cause of the sweet odor on the breath in persons with ketoacidosis. [1, 2] Ketone bodies fuel the brain with an alternative source of energy (close to two thirds of its needs) during periods of prolonged fasting or starvation, when the brain cannot use fatty acids for energy. The reference range for ketone is a negative value, at less than 1 mg/dL (< 0.1 mmol/L). [3] 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 >>

1 Ketones In Urine Summary

1 Ketones In Urine Summary

Ketones in urine, or ketonuria, as the name suggests, is characterized by the presence of ketones or ketone bodies in the urine. Ketones build up in the body when fat cells are burned to produce energy. This can be a dangerous condition if the amount of ketone is very high, particularly in people with diabetes who have high glucose levels. Carbohydrates, fats, and proteins are metabolized by the body for the generation of energy, which is used for various metabolic and enzymatic processes within the cells. On a priority basis, carbohydrates are always metabolized for the production of energy. This is then followed by the metabolization of fats and proteins. However, in some instances when the body starts generating high proportions of energy by metabolizing fats or fatty acids, a waste product of this activity accumulates in the body, which is called ketone bodies. This is usually associated with a lack of sugar or carbohydrates in the diet. These ketones are known to be eliminated through the kidneys. Hence, doctors usually perform urine tests to identify the presence of excessive ketones in the body. The concentration of ketone bodies in the urine under normal conditions is less than 20mg/dl. However, if this value rises to abnormal levels, it could be indicative of a condition known as ketoacidosis. Some of the common symptoms of ketonuria are: Thirst: The body loses excess fluid during the increased excretion of ketones. This leads to increased thirst. Frequent urination: The body tries to excrete accumulated ketones, which are associated with an increased urge to urinate. Nausea or vomiting: As the body tries to get rid of excess amounts of ketones through urine, it increases the excretion of salts like sodium and potassium. Low levels of sodium and potassium may l 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 >>

Understanding Ketones And Low-carbohydrate Diets

Understanding Ketones And Low-carbohydrate Diets

A common misunderstanding regarding the metabolic effects of low-carbohydrate diets concerns the formation of ketone bodies. The presence of ketones caused by fat burning is often confused with ketoacidosis resulting from uncontrolled diabetes, starvation or certain alcoholic conditions. Dietary ketones are more common than most people realize. As well as being caused by low-carbohydrate eating, they will occur as a result of any weight-loss plan when fat is burned or even after an overnight fast. Ketones and Evolution Ketones are produced when fat is utilized to meet energy needs. This happens when the diet comprises less than approximately 50 grams of carbohydrates per day. Ketones are a source of energy for the heart muscle and a backup fuel source for the brain. It is because of our bodies’ ability to utilize stored fat in times of a limited food supply that the human species has survived. This ability to safely use ketones preserves lean body mass while providing fuel for the brain. Ketoacidosis or Dietary Ketones Diabetic ketoacidosis occurs when blood glucose levels are exceedingly high because insulin levels are too low. The inability of the body to handle such high levels of glucose leads to a large production of acid compounds that the body is unable to neutralize. Dehydration occurs as the body loses large amounts of water through the urine attempting to remove excess glucose. This combination of circumstances leads to a life-threatening acidosis. To clear up the misconception and confusion common among many people (including the medical profession), one does not get acidosis simply by having ketones from controlling carbs. Note that one can be burning fat without excreting ketones in the urine. The excess ketones not used for energy are excreted. I think t Continue reading >>

Why I Stopped Testing My Ketones On A Ketogenic Diet

Why I Stopped Testing My Ketones On A Ketogenic Diet

On measuring Ketones. Like many people, when I first started a Ketogenic diet in early 2014 I bought the Ketostix and just couldn’t wait to see the color change. And change it did! It was neat, and it provided motivation for me to continue. Eventually, I got a blood meter, a breath meter and spent lots of time (and money) testing ketones. Between a Ketonix Breath Ketone Analyzer, as well as dozens of blood ketone test strips, I’ve probably spent well over $500 testing ketones. The main thing I learned from my extensive ketone testing regimen is that the results vary widely and there’s little application to my goals. Eventually, I stopped testing and here are several reasons why: 1. Burning fatty acids from fat is the main benefit of a ketogenic diet On a ketogenic diet, some of the brain’s energetic demand is fueled by ketones, but the heart, muscles, etc. are fueled by fatty acids. Most of the energy we utilize both at rest and at sub-maximal exertion on a ketogenic diet is fatty acid, not ketones. Quoting Dr. Ron Rosedale on chasing ketones at the Keto Summit: “I don’t want people to have the mindset that it’s the ketones that are the benefit of the diet. They are a beneficial side effect, but the main benefit is that you are burning fatty acids from fat. The more fatty acids from fat you are burning, the less glucose you need to burn. And that’s really where you are getting the benefit…So ketones are great but the term ketogenic diet indicating that the diet is so good because you are generating all these ketones is a misinterpretation of the benefit. The main benefit is that you are burning fatty acids, and as a side effect of burning fatty acids you are producing ketones that your body can burn too!” 2. Urine Ketones aka “peetones” are ridic Continue reading >>

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