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How Is Ketone Bodies Formed?

What Is Ketosis?

What Is Ketosis?

Ketosis represents a state of the organism characterized by the controlled and regulated production of ketone bodies in the blood via various metabolic processes. During very low carbohydrate intake, reduced insulin levels leads to a reduction in lipogenesis and fat accumulation. After several days of fasting, glucose reserves become insufficient both for normal fat oxidation and for the proper functioning of the brain. As the central nervous system is not able to use fatty acids for its energy because they cannot cross the blood-brain barrier, it normally utilizes glucose. Low carbohydrate intake forces the brain to find alternative energy source derived from the overproduction of acetyl coenzyme A (CoA). The production of ketone bodies in a process called ketogenesis ensues. Ketosis is a completely physiological mechanism and it needs to be differentiated from the pathological ketoacidosis seen in type 1 diabetes. Physiological ketosis that arises as a result of ketogenic diets is characterized by ketone bodies in blood reaching a maximum level of 8 mmol/l with no change in pH, compared to uncontrolled diabetic ketoacidosis where their level can exceed 20 mmol/l and result in a lower blood pH. Ketone body metabolism The term “ketone bodies” refers to three specific compounds: acetone, acetoacetate and beta-hydroxybutyrate (or beta-hydroxybutyric acid). The circulating levels of ketone bodies depend both on their rate of production (i.e. ketogenesis) and their rate of utilization (i.e. ketolysis). They are of vital importance to the brain, which is unable to derive energy from other sources when blood glucose levels are low. In healthy adults, the liver is able to produce 185 grams of ketone bodies each day. The main ketone body produced is acetoacetate, but the pr Continue reading >>

Regulation Of Ketone Body And Coenzyme A

Regulation Of Ketone Body And Coenzyme A

METABOLISM IN LIVER by SHUANG DENG Submitted in partial fulfillment of the requirements For the Degree of Doctor of Philosophy Dissertation Adviser: Henri Brunengraber, M.D., Ph.D. Department of Nutrition CASE WESTERN RESERVE UNIVERSITY August, 2011 SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of __________________ ____________ _ _ candidate for the ________________________________degree *. (signed) ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. Shuang Deng (chair of the committee) Edith Lerner, PhD Colleen Croniger, PhD Henri Brunengraber, MD, PhD Doctor of Philosophy Janos Kerner, PhD Michelle Puchowicz, PhD Paul Ernsberger, PhD I dedicate this work to my parents, my son and my husband iv TABLE OF CONTENTS Table of Contents…………………………………………………………………. iv List of Tables………………………………………………………………………. viii List of Figures……………………………………………………………………… ix Acknowledgements………………â 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 >>

Wvsom -- Biochem

Wvsom -- Biochem

Ketone Bodies are produced in the ________ Flashcards Matching Hangman Crossword Type In Quiz Test StudyStack Study Table Bug Match Hungry Bug Unscramble Chopped Targets Oxidation of Ketone Bodies Question Answer Ketone Bodies are produced in the ________ Liver Is ketone body production a fed state or a fasted state event? Fasted State Are ketones toxic? Not as long as they can be used. Why is ketone body production and use in a fasted state? Liver Beta oxidizes esxcess fatty acids mobilized from adipocytes in teh fasted state. Acetyl-CoA produced by B oxidation is the "excess" carbon for hepatic ketone body synthesis What produces Acetyl CoA for ketone production? B-Oxidation and ketogenic amino acid catabolism Why can't the liver use all the acetyl CoA it produces in the fasted state? B-oxidation produces more Aceytl CoA than can be used Why can't the liver use all of the acetyl CoA it produces in the Fasted Stated The liver must devote significant oxaloacetate to gluconeogenesis so this limites the TCA cycle activity. What does teh liver obtain from its B-oxidation of excess fatty acids? FADH2 AND NADH are used by the liver without involvement of teh TCA cycle. Can go straight to oxidative phosphorylation NADH may provide "___________" for mitochondrial malate dehydrogenase’s production of malate from oxaloacetate. reducing power What does the body do with excess acetyl CoA carbons the liver cannot catabolize? The liver converts it to ketone bodies. What organs import ketone bodies? heart, kidney and skeletal muscle Why can high energy demand organs catabolize ketone bodies? they do not have the limit on their TCA cycle activity that hepatocytes do Can the liver use ketone bodies? no Can acetoacetyl CoA cross the plasma membrane? No What CoA is at a branch point of 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 >>

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 >>

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 >>

Ketone Body Formation And Utilisation  Acetoacetate,  -hydroxy Butyrate And Acetone Are Collectively Called As Ketone Bodies.  The Process Of Formation.

Ketone Body Formation And Utilisation  Acetoacetate,  -hydroxy Butyrate And Acetone Are Collectively Called As Ketone Bodies.  The Process Of Formation.

Presentation on theme: "Ketone body formation and utilisation  Acetoacetate,  -hydroxy butyrate and acetone are collectively called as ketone bodies.  The process of formation."— Presentation transcript: 1 Ketone body formation and utilisation  Acetoacetate,  -hydroxy butyrate and acetone are collectively called as ketone bodies.  The process of formation of ketone bodies in the liver is called ketogenesis.  Blood level is usually less than 2 mg % in well-fed state.  Increased production of ketone bodies is known as ketosis.  High level of ketone bodies in blood are referred to as ketonemia  More ketone bodies in the urine is called as ketonuria.  Lungs mainly eliminate acetone. The acetyl CoA formed in fatty acid oxidation enters into TCA cycle only if fat and carbohydrate degradation are appropriately balanced 2 Conditions in which ketone body formation are Prolonged starvation: During starvation the carbohydrate level will be low. So the stored fat of the adipose tissue break down to free fatty acids. The free fatty acids formed enter the liver and undergoes  - oxidation to release acetyl CoA which cannot be utilized by the liver through TCA cycle due to lack of Oxaloacetate. In starvation TCA cycle is impaired due to the deficiency of oxaloacetate which is diverted to glucose synthesis (gluconeogenesis). Therefore acetyl CoA converted to ketone bodies to meet the energy needs. 3 Uncontrolled diabetes mellitus: Because of the lack of insulin the carbohydrate metabolism is impaired The adipose tissue fat becomes the main source of energy and its degradation is generally accelerated. This results in the excessive production of acetyl CoA, leading to accumulation of acetyl CoA and its conversion to ketone bodies Feeding high fat die 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 >>

Fenofibrate Induces Ketone Body Production In Melanoma And Glioblastoma Cells

Fenofibrate Induces Ketone Body Production In Melanoma And Glioblastoma Cells

1Department of Food Biotechnology, Faculty of Food Technology, University of Agriculture, Krakow, Poland 2Molecular and Metabolic Oncology Program, Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL, USA 3Department of Human Nutrition, Faculty of Food Technology, University of Agriculture, Krakow, Poland 4Neurological Cancer Research, Stanley S Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA Ketone bodies [beta-hydroxybutyrate (bHB) and acetoacetate] are mainly produced in the liver during prolonged fasting or starvation. bHB is a very efficient energy substrate for sustaining ATP production in peripheral tissues; importantly, its consumption is preferred over glucose. However, the majority of malignant cells, particularly cancer cells of neuroectodermal origin such as glioblastoma, are not able to use ketone bodies as a source of energy. Here, we report a novel observation that fenofibrate, a synthetic peroxisome proliferator-activated receptor alpha (PPARa) agonist, induces bHB production in melanoma and glioblastoma cells, as well as in neurospheres composed of non-transformed cells. Unexpectedly, this effect is not dependent on PPARa activity or its expression level. The fenofibrate-induced ketogenesis is accompanied by growth arrest and downregulation of transketolase, but the NADP/NADPH and GSH/GSSG ratios remain unaffected. Our results reveal a new, intriguing aspect of cancer cell biology and highlight the benefits of fenofibrate as a supplement to both canonical and dietary (ketogenic) therapeutic approaches against glioblastoma. 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 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 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 >>

21.3. Formation Of Ketone Bodies And Degradation Of Ketone Bodies.

21.3. Formation Of Ketone Bodies And Degradation Of Ketone Bodies.

154 Either for the generation of more NADH and FADH2 by entering into Krebs cycle and produce ATP. or transported for the generation of ketone bodies which are used by other tissues as energy source. For the formation of ketone bodies 2 molecules of Acetyl CoA are condensed into acetoacetyl CoA which is further processed and converted to b hydroxybutyrate. Alpha oxidation – it is an alternative form of lipid oxidation. It does not require the activation of fatty acid. COOH group of lipid is decarboxylated and then this undergoes the cycle of oxidation. This oxidation occurs for the synthesis of -OH fatty acid like cerebronic acid which constitutes cerebrosides in brain. It oxidize phytanic acid which is produced by dietry phytols of chlorophyll by phytate -oxidase and pristanic acid is oxidized by - oxidation. Defect in a oxidation causes a rare genetic disorder Refsum disease in which deficiency of phytate a oxidase enzyme. omega () oxidation – It is found in liver and microsomes. It causes the hydroxylation of omega carbon. Peroxisomal fatty acid oxidation – it is a modified form of oxidation in which acetyl CoA and H2O2 is formed as final products. This pathway does not generate ATP. Zellweger Syndrome is the condition of absence of peroxisome in all the cells of body so the patient is unable to oxidize long fatty acid chains of C26–C38. 21.5. Lipid synthesis Synthesis of fatty acids is catalyzed by fatty acid synthase which is a multifunctional enzyme. This enzyme is located in the cytoplasm which acts upon the acetyl CoA as a primer molecule. NADPH is used reducing agent in this reaction. Fatty acid synthase enzyme catalyzes all the seven reactions of this process. It is a homodimer contains two identical peptide chains. Every reaction catalyzed by a specif Continue reading >>

Ketone Bodies

Ketone Bodies

Abstract Ketone bodies are water‐soluble equivalents of fatty acids. They can substitute for glucose in peripheral tissues, especially in the brain, when glucose becomes limited in physiological and pathological states. Recent findings demonstrate that they also act as signalling metabolites, thus participating in the organism adaptation to the environment, such as during fasting, calorie restriction or prolonged exercise. Diabetes is the most common pathological cause of elevated blood ketone bodies. Ketone bodies are produced in excess in response to low insulin levels and high levels of counterregulatory hormones, the result being the development of metabolic acidosis that is associated with serious health complications. Yet, ketogenic diets have been used for decades to increase ketone body synthesis for their neuroprotective properties as central signalling metabolites and as main energy‐providing substrate for the brain, in epilepsy and neurodegenerative diseases. Key Concepts Ketone bodies are key energy substrates and signalling molecules Ketone bodies participate in energy homeostasis Diabetic ketoacidosis is the most common pathological cause of elevated blood ketone bodies and is associated with serious health complications Ketone bodies are neuroprotective Ketone bodies offer promising perspectives in clinical therapy for certain metabolic diseases, neurodegenerative diseases and cancers Keywords: ketone bodies; energy homeostasis; starvation; exercise; ketoacidosis; neuroprotection Continue reading >>

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