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Ketogenesis

Ketogenesis – It’s All About Blood Sugar

Ketogenesis – It’s All About Blood Sugar

I’ve been on the ketogenic diet for over a year now and decided to have a week of moderate carb intake to see what effect it would have on staying in the ketozone. I define ketozone as the perfect blend of blood sugar and blood ketones resulting in a Glucose/Ketone index of 1 or below. In medical terms this shows a state of ketosis where cancer cells are deprived of their food supply. In other words, you’re starving cancer to death. I didn’t just jump off the wagon and start eating every carb I could find. I added about 100 grams of carbs to my diet, mostly from starchy veggies and a few grains. I’ll admit I celebrated with a few pieces of toast with my eggs. I ate some long fermented sourdough bread and even some gluten free bread. Still, I didn’t eat excessively and didn’t gain a pound. But what I noticed was pretty alarming. My blood sugar jumped from an average of 75-80 to 125 which is diabetic stage. My ketones dropped from an average of 4 to an average of .4—a huge drop. No matter how many tricks I tried to raise my ketones nothing worked. I decided I better go back to ground zero. I fat fasted for 40 hours which means I basically stopped eating at 7pm and didn’t eat food again until 11am 2 days later. I did consume some MCT oil and butter during my fast, since this doesn’t trigger an insulin response your body still goes through the process of using up blood sugar. I tested myself that day and my blood sugar reversed. I went from 125 to 72, and my ketones went up to 5.2 from .4. I was able to go back into ketosis and regulate my sugar in just one and a half days of dieting. During the carb week nothing I did would raise my ketones. When my sugar dropped my ketones shot way up. My body regulates itself really well on a low carb, high fat diet. It Continue reading >>

Disorders Of Ketogenesis And Ketolysis

Disorders Of Ketogenesis And Ketolysis

Disorders of ketone body metabolism are characterized by episodes of metabolic decompensation. The initial episode usually occurs in the newborn period or early childhood during an infection with vomiting. The disorders of ketogenesis cause hypoglycemia and encephalopathy. Decompensation leads to severe ketoacidosis in defects of ketone body utilization (including MCT1 transporter deficiency). Treatment aims to prevent the catabolism that leads to decompensation. Prolonged fasting is avoided and glucose is provided, orally or intravenously, during illnesses. The risk of decompensation falls with age, particularly for disorders of ketolysis. There have, however, been some fatal episodes in adults with HMG-CoA lyase deficiency, including during pregnancy. Access to the complete content on Oxford Medicine Online requires a subscription or purchase. Public users are able to search the site and view the abstracts for each book and chapter without a subscription. Please subscribe or login to access full text content. If you have purchased a print title that contains an access token, please see the token for information about how to register your code. For questions on access or troubleshooting, please check our FAQs, and if you can't find the answer there, please contact us. Glut1 Deficiency (Glut1D, OMIM #606777) is caused by impaired glucose transport into the brain. The resulting cerebral “energy crisis” causes intractable seizures, developmental delay, and a complex movement disorder. The diagnosis is based on clinical features, low CSF glucose and/or mutations in the SLC2A1 gene. Paroxysmal exertion-induced dystonia (PED) and hereditary cryohydrocytosis have been described as allelic variants. Adults are increasingly being recognized through family pedigrees. The con Continue reading >>

During This Time, The Biocyc Websites

During This Time, The Biocyc Websites

SRI International will be closed from close of business 22 Dec 2017 until opening of business 2 Jan 2018. Support issues logged while SRI is closed will be addressed when we re-open. (EcoCyc, HumanCyc, MetaCyc, BsubCyc) will be down for maintenance until noon Sunday, 31 Dec 2017 All times Pacific Standard Time Continue reading >>

What Is Ketogenesis?

What Is Ketogenesis?

In physiological conditions, the human body derives its energy from the aerobic oxidation of liver glycogen (a polymer of glucose) in the Krebs Cycle. The reserve of glycogen in the liver ensures energy supply for one day. Once hepatic glucose stores are depleted, the body has to find another 'fuel' to produce energy. Skeletal muscles and all other parts of the human body, the nervous system excluded, extract energy from acetyl-CoA, which is the result of Beta oxidation of fatty acids. The brain, instead, can only derive energy from glucose. In order to provide energy to the brain, the liver uses the process of gluconeogenesis. It consists in the formation 'ex novo' of glucose molecules that the brain can use as energy source. The process of gluconeogenesis starts from the 'oxaloacetate' molecule. Oxaloacetate is obtained by changing the carbon backbone of many amino acids (in red in the figure) through enzymatic reactions that are part of the Krebs cycle This process, in the liver causes: - Endogenous biosynthesis of glucose, using carbon skeletons of ‘glucogenic’amino acids as glucose precursors' (The structure of glucogenic aminoacids can be converted, through enzymatic reactions, into oxaloacetate, and consequently into glucose). - Surplus of Acetyl CoA, which is the second reagent of the first stage of Krebs cycle. At this purpose, to be able to reach extrahepatic tissues, it must be converted into blood solubile molecules. These molecules are the so called ketone bodies. Liver enzymes convert two molecules of Acetyl CoA into acetoacetate. Later, from this reaction, two more ketone bodies, acetone and D-beta hydroxybutyrate, will be formed. Ketone bodies are highly energetic compounds that, circulating in the blood, reach extra hepatic tissues (skeletal muscle, Continue reading >>

Ketogenesis

Ketogenesis

Also found in: Dictionary, Encyclopedia, Wikipedia. Related to ketogenesis: ketogenic diet ketogenesis [ke″to-jen´ĕ-sis] the production of ketone bodies. adj., adj ketogen´ic, ketogenet´ic. Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. © 2003 by Saunders, an imprint of Elsevier, Inc. All rights reserved. ke·to·gen·e·sis (kē'tō-jen'ĕ-sis), Metabolic production of ketones or ketone bodies. ketogenesis /ke·to·gen·e·sis/ (-jen´ĕ-sis) the production of ketone bodies.ketogenet´icketogen´ic ketogenesis the formation or production of ketone bodies. ke·to·gen·e·sis (kē'tō-jen'ĕ-sis) Metabolic production of ketones or ketone bodies. ketogenesis The formation of acid KETONE BODIES, as in uncontrolled DIABETES, starvation or as a result of a diet with a very high fat content. ketogenesis the production of ketone bodies which occurs particularly during starvation. Continue reading >>

The Biochemistry Of Ketogenesis And Its Role In Weight Management, Neurological Disease And Oxidative Stress

The Biochemistry Of Ketogenesis And Its Role In Weight Management, Neurological Disease And Oxidative Stress

Abstract Ketogenesis is the branch of mammalian metabolism concerned with the synthesis of ketone bodies. In this process, the small, water-soluble compounds acetoacetate, D-3-β-hydroxybutyrate and propanone are produced by the liver in response to reduced glucose availability. Although ketone bodies are always present at a low level in healthy individuals, dietary manipulation and certain pathological conditions can increase the levels of these compounds in vivo. In some instances, such as in refractory epilepsy, high levels of ketone bodies can be beneficial—in this instance, by exerting an anticonvulsant effect. Conversely, if the levels of ketones rise to supraphysiological levels, as can occur in diabetes mellitus, a state of ketoacidosis can occur, which has serious consequences for cellular function. More recently, research has identified a possible link between ketogenesis and free radical-mediated pathologies, highlighting the potential application of ketogenic diets to the treatment of conditions such as Alzheimer's disease. Overall, an understanding of ketone body metabolism and its links to human disease may prove to be vital in developing new regimens for the treatment of human disease. Notes This work was partially supported by the Northern Ireland R&D Office (Extension to RRG 5.42). The authors would like to thank Dr DJ Timson, School of Biological Sciences, Queen's University Belfast, for useful discussions of mammalian metabolism. Continue reading >>

The Regulation Of Ketogenesis.

The Regulation Of Ketogenesis.

Abstract Ketone bodies accumulate in the plasma in conditions of fasting and uncontrolled diabetes. The initiating event is a change in the molar ratio of glucagon:insulin. Insulin deficiency triggers the lipolytic process in adipose tissue with the result that free fatty acids pass into the plasma for uptake by liver and other tissues. Glucagon appears to be the primary hormone involved in the induction of fatty acid oxidation and ketogenesis in the liver. It acts by acutely dropping hepatic malonyl-CoA concentrations as a consequence of inhibitory effects exerted in the glycolytic pathway and on acetyl-CoA carboxylase (EC 6.4.1.2). The fall in malonyl-CoA concentration activates carnitine acyltransferase I (EC 2.3.1.21) such that long-chain fatty acids can be transported through the inner mitochondrial membrane to the enzymes of fatty acid oxidation and ketogenesis. The latter are high-capacity systems assuring that fatty acids entering the mitochondria are rapidly oxidized to ketone bodies. Thus, the rate-controlling step for ketogenesis is carnitine acyltransferase I. Administration of food after a fast, or of insulin to the diabetic subject, reduces plasma free fatty acid concentrations, increases the liver concentration of malonyl-CoA, inhibits carnitine acyltransferase I and reverses the ketogenic process. Continue reading >>

6 Health Benefits Of Ketogenesis And Ketone Bodies

6 Health Benefits Of Ketogenesis And Ketone Bodies

With heavy coverage in the media, ketogenic diets are all the rage right now. And for a good reason; for some people, they truly work. But what do all these different terms like ketogenesis and ketone bodies actually mean? Firstly, this article takes a look at what the ketogenesis pathway is and what ketone bodies do. Following this, it will examine six potential health benefits of ketones and nutritional ketosis. What is Ketogenesis? Ketogenesis is a biochemical process through which the body breaks down fatty acids into ketone bodies (we’ll come to those in a minute). Synthesis of ketone bodies through ketogenesis kicks in during times of carbohydrate restriction or periods of fasting. When carbohydrate is in short supply, ketones become the default energy source for our body. As a result, a diet to induce ketogenesis should ideally restrict carb intake to a maximum of around 50 grams per day (1, 2). Ketogenesis may also occur at slightly higher levels of carbohydrate intake, but for the full benefits, it is better to aim lower. When ketogenesis takes place, the body produces ketone bodies as an alternative fuel to glucose. This physiological state is known as ‘nutritional ketosis’ – the primary objective of ketogenic diets. There are various methods you can use to test if you are “in ketosis”. Key Point: Ketogenesis is a biological pathway that breaks fats down into a form of energy called ketone bodies. What Are Ketone Bodies? Ketone bodies are water-soluble compounds that act as a form of energy in the body. There are three major types of ketone body; Acetoacetate Beta-hydroxybutyrate Acetone (a compound created through the breakdown of acetoacetate) The first thing to remember is that these ketones satisfy our body’s energy requirements in the same w Continue reading >>

How Ketogenesis And Ketones Treat Inflammation

How Ketogenesis And Ketones Treat Inflammation

Intro Inflammation is a biological mechanism our bodies use to deal with internal and external events, such as combatting infections, repairing tissues or mitigating the immediate consequences of a fractured bone. However, it often carries a negative connotation since many diseases provoke symptoms through the process of inflammation. So although it is absolutely necessary for keeping the human body functioning properly, like so many things in biology, too much or too little is the problem. Inflammation can be managed with and without drugs. Here we will focus on ketogenesis and ketones with regards to treating inflammation since both drug and drug-free approaches can be discussed. What is ketogenesis? Ketogenesis is the process whereby your body produces molecules called ketone bodies, also known as ketones (see What’s a Ketone?). More specifically, ketogenesis is a series of biochemical reactions that builds molecules (ketones) from parts of other ones (like 2 acetyl-CoA molecules). How ketone bodies are formed? Fellow nerds can gaze upon the ketogenesis pathway below (1) whilst the non-initiated can simply keep in mind that our liver is ground-zero for ketogenesis. This is where fat is used as the raw material to produce 3 kinds of ketone bodies. Humans are remarkably good at ketogenesis. Just for comparison, dogs too can make ketones but the degree to which they require protein, carbohydrate or caloric restriction to do so is greater (2,3). Once you’ve produced enough ketones by upregulating ketogenesis, you eventually move into a metabolic state called ketosis. People are in ketosis when they are on a diet low enough in carbohydrates, known as a ketogenic diet, or when eating very very little if any food at all for example. What a ketogenic diet and fasting hav Continue reading >>

No Net Synthesis

No Net Synthesis

·Standard AAs are degraded to one of 7 metabolic intermediates: pyruvate; a-ketoglutarate; succinyl-CoA; fumarate; oxaloacetate; acetyl-CoA; or acetoacetate. ·In animals, Leucine and Lysine are the only two purely ketogenic AAs (i.e. they can be converted to acetoacetate or acetyl-CoA; no net synthesis of pyruvate or any of the TCA intermediates). ·Five AAs (Isoleucine; Threonine; Phenylalanine; Tyrosine; Tryptophan) are both glucogenic (i.e. they are first converted to pyruvate or any of the TCA intermediates) and ketogenic. ·13 other AAs are purely glucogenic. (Chapter 19, section 3, pp. 649-650. Fig. 19-21) ·A mitochondrial process by which acetyl-CoA is converted to acetoacetate and D-β-hydroxybutyrate. ·Ketone Bodies: acetoacetate, D-β-hydroxybutyrate, and acetone. ·Ketone bodies are water-soluble equivalents of fatty acids. ·Important metabolic fuels for peripheral tissues, especially heart and skeletal muscle. ·The brain utilizes glucose for energy under normal circumstances. However, ketone bodies become brain’s major fuel source during starvation. A. Formation of Acetoacetate in Mitochondria ·Thiolase ·Hydroxymethylglutaryl-CoA synthaseb-Hydroxymethylglutaryl-CoA (Corresponding enzymes also exist in cytosol which, together with HMG-CoA reductase, function in mevalonate synthesis.) ·HMG-CoA Lyase B. Formation of D-β-Hydroxybutyrate ·β-Hydroxybutyrate Dehydrogenase Note: enoyl-CoA hydratase 3-L-hydroxyacyl-CoA DH trans-∆2-enoyl-CoA→L-β-hydroxyacyl-CoA→β-ketoacyl-CoA β-ketoacyl-ACP→D- β-hydroxyacyl-ACP→trans-∆2-enoyl-ACP C. Formation of Acetone (by a facile nonenzymatic reaction) ======================================================= Utilization of Ketone Bodies (Fig. 19-22) Liver releases acetoacetate and β-hydroxybutyrate → Continue reading >>

Ketogenesis Prevents Diet-induced Fatty Liver Injury And Hyperglycemia

Ketogenesis Prevents Diet-induced Fatty Liver Injury And Hyperglycemia

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are now the most common causes of liver disease in Western countries (1). NAFLD-induced liver failure is one of the most common reasons for liver transplantation. NAFLD increases the risk of developing type 2 diabetes, worsens glycemic control, and contributes to the pathogenesis of cardiovascular disease and chronic kidney disease (2–4). The pathogenic mechanisms of NAFLD and NASH are incompletely understood but are thought to involve abnormalities of hepatocyte metabolism, hepatocyte autophagy and endoplasmic reticulum stress, hepatic immune cell function, adipose tissue inflammation, and systemic inflammatory mediators (2, 4–6). Perturbations of carbohydrate, lipid, and amino acid metabolism occur in and contribute to obesity, diabetes, and NAFLD in humans and in model organisms (reviewed in refs. 7–11). While hepatocyte abnormalities in cytoplasmic lipid metabolism are commonly observed in NAFLD (12), the role of mitochondrial metabolism, which governs the oxidative and terminal “disposal” of fats, in NAFLD pathogenesis is less clear. Nonetheless, most investigators agree that abnormalities of mitochondrial metabolism occur in and contribute to NAFLD (reviewed in refs. 13–15). Ketogenesis can dispose of as much as two-thirds of the fat entering the liver (16). Thus, dysregulation of ketone body metabolism could potentially contribute to NAFLD pathogenesis. Hepatic ketogenesis is activated in states of high fatty acid and diminished carbohydrate availability and/or when circulating insulin concentrations are very low (17–20). Within hepatic mitochondria, ketogenic reactions condense β-oxidation–derived acetyl-CoA into the ketone bodies acetoacetate (AcAc) and β hydroxyb 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 >>

Ketogenesis

Ketogenesis

What is Ketogenesis? Ketogenesis (1, 2) is a biochemical process that produces ketone bodies by breaking down fatty acids and ketogenic amino acids. The process supplies the needed energy of certain organs, especially the brain. Not having enough ketogenesis could result to hypoglycaemia and over production of ketone bodies leading to a condition called ketoacidosis. It releases ketones when fat is broken down for energy. There are many ways to release ketones such as through urination and exhaling acetone. Ketones have sweet smell on the breath. (3) Ketogenesis and ketoacidosis are entirely different thing. Ketoacidosis is associated with diabetes and alcoholism, which could lead to even serious condition like kidney failure and even death. Picture 1 : Ketogenic pathway Photo Source : medchrome.com Image 2 : A pyramid of ketogenic diet Photo Source : www.healthline.com What are Ketone bodies? Ketone bodies are water soluble molecules produced by the liver from fatty acids during low food intake or fasting. They are also formed when the body experienced starvation, carbohydrate restrictive diet, and prolonged intense exercises. It is also possible in people with diabetes mellitus type 1. The ketone bodies are picked up by the extra hepatic tissues and will convert to acetyl-CoA. They will enter the citric acid cycle and oxidized in the mitochondria to be used as energy. Ketone bodies are needed by the brain to convert acetyl-coA into long chain fatty acids. Ketone bodies are produced in the absence of glucose. (1, 2, 3) It is easy to detect the presence of ketone bodies. Just observe the person’s breath. The smell of the breath is fruity and sometimes described as a nail polish remover-like. It depicts the presence of acetone or ethyl acetate. The ketone bodies includ Continue reading >>

Fatty Acid Oxidation And Ketogenesis

Fatty Acid Oxidation And Ketogenesis

transport in the blood a) adipose tissue: fat catabolism (lipolysis) -fat --> glycerol + 3 FFA -hormone sensitive lipase: breakdown fat in our internal stores -fasting (glucagon) and physical activity (epinephrine) b) FFA (unesterified or nonesterified) bind to albumin in the blood while glycerol is free and it circulates in the blood until it gets to the cells that need energy, enters the cell cytosol and stays there while FA doesnt because FA needs to move to mitochondria to be used as an energy source. glycerol is water soluble (composed of 3 carbon and 3 alcohol groups) c) in the cell, FFA binds to fatty acid-binding protein fatty acid oxidation we need to convert FA to acetyl CoA so we can use them in citric acid cylce as energy source FA--> acetyl CoA to do this reaction, mitochondria, and NAD(niacin), FAD (riboflavin) are needed as coenzymes formation of acetyl CoA is going to occur under below conditions, what happens to Acetyl CoA is different in all these situations: low carb diet, fasting, starvation, type I diabetes, exercise) beta-oxidation step 3 of activation of FFA acylcarnitine transported thru inner membrane by a protein -carnitine acylcarnitine translocase carnitine is used first because for every acylcarnitine that goes through inside the mitochondria, a molecule of free carnitine has to be transported outside the membrane simultaneouly to do the previous reaction for the next fatty acid, recyling carnitine we are transferring acylcarnitine through the membrane space to inner membrane (inside the matrix of mitochondria) beta oxidation formation of acetyl CoA from carboyxl end of FA, repeating until FA is completely oxidized fatty acid oxidases: enzymes involved in the oxidation process once the fatty acid is inside the mitochondria (acyl CoA), we can Continue reading >>

Lipid Metabolism And Ketogenesis

Lipid Metabolism And Ketogenesis

With Picmonic, facts become pictures. We've taken what the science shows - image mnemonics work - but we've boosted the effectiveness by building and associating memorable characters, interesting audio stories, and built-in quizzing. Lips with Metal-balls and Key-genie Picmonic Lipid metabolism is composed of catabolic processes that generate energy and anabolic processes that create biologically important molecules, such as triglycerides, phospholipids, second messengers, local hormones and ketone bodies. Ketogenesis is the process of breaking down fatty acids in order to produce ketone bodies, such as acetoacetate, acetone, and beta-hydroxybutyrate. Picmonic for Medicine (MD/DO) covers information that is relevant to your entire Medical (MD/DO) education. Whether you’re studying for your classes or getting ready to conquer the USMLE Step 1, USMLE Step 2 CK, COMLEX Level 1, or COMLEX Level 2, we’re here to help. Research shows that students who use Picmonic see a 331% improvement in memory retention and a 50% improvement in test scores. "[Picmonics] correlate directly with what is in First Aid so you know it is essential information that will show up on the exam. The number of questions I got right in biochemistry and microbiology were mainly due to this resource." James, Texas Tech University Health Sciences Center School of Medicine, 274 on Step 1 TRY IT FREE Continue reading >>

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