Acetyl Coa - Cross Roads Compound
Metabolic Fates of Acetyl CoA: If you reflect on both the content lipid metabolism and the previous carbohydrate metabolism, you can appreciate that there is a special central role for acetyl CoA. Acetyl CoA acts both as a metabolic "receiving and shipping department" for all classes of biomolecules and as a major source of useful metabolic energy. The diagram on the left summarizes all metabolism and the central role of acetyl CoA. The diagram the next lower panel focuses on other functions as well. The interactions of amino acids with acetyl CoA and the citric acid cycle will be studied in protein metabolism. Notice that acetyl CoA can react "reversibly" in the degradation or synthesis of lipids and amino acids. This is not the case with carbohydrate metabolism. In mammals, it is impossible to use acetyl CoA to make carbohydrates. Synthesis of Cholesterol and other Steroids: Without going into detail, acetyl CoA forms the basis from which the fairly complicated steroids are synthesized. Some steroids of importance include cholesterol, bile salts, sex hormones, aldosterone, and cortisol. The major concern about cholesterol in the diet is muted somewhat by the knowledge that the liver can and does synthesize all of the cholesterol that the body needs. Excess cholesterol, whether from food or synthesized by the liver, ends up in the blood stream where it builds up on the artery walls. It has been determined that cholesterol levels can be controlled by lowering the amount of saturated fat and increasing the unsaturated fats. Unsaturated fats seem to speed the rate at which cholesterol breaks down in the blood. Controlling fats and cholesterol in the diet can significantly affect the levels of these substances in the blood. Lipogenesis: Since carbohydrates are the major pa Continue reading >>
Ketogenesis pathway. The three ketone bodies (acetoacetate, acetone, and beta-hydroxy-butyrate) are marked within an orange box Ketogenesis is the biochemical process by which organisms produce a group of substances collectively known as ketone bodies by the breakdown of fatty acids and ketogenic amino acids. This process supplies energy to certain organs (particularly the brain) under circumstances such as fasting, but insufficient ketogenesis can cause hypoglycemia and excessive production of ketone bodies leads to a dangerous state known as ketoacidosis. Production Ketone bodies are produced mainly in the mitochondria of liver cells, and synthesis can occur in response to an unavailability of blood glucose, such as during fasting. Other cells are capable of carrying out ketogenesis, but they are not as effective at doing so. Ketogenesis occurs constantly in a healthy individual. Ketogenesis takes place in the setting of low glucose levels in the blood, after exhaustion of other cellular carbohydrate stores, such as glycogen. It can also take place when there is insufficient insulin (e.g. in type 1 (but not 2) diabetes), particularly during periods of "ketogenic stress" such as intercurrent illness. The production of ketone bodies is then initiated to make available energy that is stored as fatty acids. Fatty acids are enzymatically broken down in β-oxidation to form acetyl-CoA. Under normal conditions, acetyl-CoA is further oxidized by the citric acid cycle (TCA/Krebs cycle) and then by the mitochondrial electron transport chain to release energy. However, if the amounts of acetyl-CoA generated in fatty-acid β-oxidation challenge the processing capacity of the TCA cycle; i.e. if activity in TCA cycle is low due to low amo Continue reading >>
What Are The Advantages Of Eating A High-fat Diet For Weight Loss, Rather Than Simply Fasting?
You can actually do both and lose weight very effectively, in addition to gaining many other health benefits. As someone else mentioned, the ketogenic diet actually is not a fad diet but has research to prove its effectiveness, and I personally have seen its benefits. Many also incorporate intermittent fasting with keto, but it’s not a requirement. I do recommend watching some of Dr. Jason Fung’s videos on fasting for really interesting information on how fasting intermittently can be very healthy in a lot of ways. So if you’re not familiar, the keto diet has the optimum ratios of macronutrients: fat, protein, and carbohydrates. There has been a great deal of debate in recent years on what those ratios should be, and it does vary from person to person. However, research is showing that what we were led to believe in the past, that eating fat makes you fat, is dead wrong. Eating a diet high in fat, moderate in protein, and very low in carbohydrates, such as the ketogenic diet (or commonly known as “keto”), puts your body into a state of ketosis, a natural metabolic state in which your body is no longer using glucose as its main source of fuel, and instead it begins using ketones to get its energy. Ketones are produced when your body is burning fat because no glucose is available. It is important not to confuse ketosis, a completely harmless and normal metabolic state, with ketoacidosis, a dangerous condition that occurs mostly in type 1 diabetics when they create high levels of both glucose and ketones at the same time. On the ketogenic plan, blood glucose usually drops, so this is not a danger for most people. However, if you are a type 1 diabetic, check with your doctor before switching to the ketogenic way of eating. So being in ketosis simply means that you Continue reading >>
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Definition: Acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main use is to convey the carbon atoms within the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for energy production. Its is the base of the biosynthesis of fatty acids and cholesterol. Acetyl-CoA is also an important component in the biogenic synthesis of the neurotransmitter acetylcholine. Choline, in combination with Acetyl-CoA, is catalyzed by the enzyme choline acetyltransferase to produce acetylcholine and a coenzyme a byproduct. Structure In chemical structure, acetyl-CoA is the thioester between coenzyme A (a thiol) and acetic acid (an acyl group carrier). Acetyl-CoA is produced during the second step of aerobic cellular respiration, pyruvate decarboxylation, which occurs in the matrix of the mitochondria. Acetyl-CoA then enters the citric acid cycle (Krebs cycle). Metabolism Acetyl-CoA is produced in mitochondria through the metabolism of fatty acids and the oxidation of pyruvate to acetyl-CoA. When ATP is needed, this acetyl-CoA can enter the Krebs cycle to drive oxidative phosphorylation. When ATP supplies are abundant, the acetyl-CoA can be diverted to other purposes like energy storage in the form of fatty acids. The biosynthesis of fatty acids from this acetyl-CoA cannot take place directly however, since it is produced inside mitochondria while fatty acid biosynthesis occurs in the cytosol. There is not a mechanism that directly transports acetyl-CoA out of mitochondria. To be transported, the acetyl-CoA must be chemically converted to citric acid using a pathway called the tricarboxylate transport system. Inside mitochondria, the enzyme citrate synthase joins acetyl-CoA with oxaloacetate to make citrate. This citrate is transported Continue reading >>
Diabetes And Ketones
Tweet The presence of high levels of ketones in the bloodstream is a common complication of diabetes, which if left untreated can lead to ketoacidosis. Ketones build up when there is insufficient insulin to help fuel the body’s cells. High levels of ketones are therefore more common in people with type 1 diabetes or people with advanced type 2 diabetes. If you are suffering from high levels of ketones and seeking medical advice, contact your GP or diabetes healthcare team as soon as possible. What are ketones? Ketones are an acid remaining when the body burns its own fat. When the body has insufficient insulin, it cannot get glucose from the blood into the body's cells to use as energy and will instead begin to burn fat. The liver converts fatty acids into ketones which are then released into the bloodstream for use as energy. It is normal to have a low level of ketones as ketones will be produced whenever body fat is burned. In people that are insulin dependent, such as people with type 1 diabetes, however, high levels of ketones in the blood can result from taking too little insulin and this can lead to a particularly dangerous condition known as ketoacidosis. How do I test for ketones? Ketone testing can be carried out at home. The most accurate way of testing for ketones is to use a blood glucose meter which can test for ketones as well as blood glucose levels. You can also test urine for ketone levels, however, the testing of urine means that the level you get is representative of your ketone levels up to a few hours ago. Read about testing for ketones and how to interpret the results Who needs to be aware of ketones? The following people with diabetes should be aware of ketones and the symptoms of ketoacidosis: Anyone dependent on insulin – such as all people Continue reading >>
Introduction To Degradation Of Lipids And Ketone Bodies Metabolism
Content: 1. Introduction to degradation of lipids and ketone bodies metabolism 2. Lipids as source of energy – degradation of TAG in cells, β-oxidation of fatty acids 3. Synthesis and utilisation of ketone bodies _ Triacylglycerol (TAG) contain huge amounts of chemical energy. It is very profitable to store energy in TAG because 1 g of water-free TAG stores 5 times more energy than 1 g of hydrated glycogen. Complete oxidation of 1 g of TAG yields 38 kJ, 1g of saccharides or proteins only 17 kJ. Man that weighs 70 kg has 400 000 kJ in his TAG (that weight approximately 10,5 kg). This reserve of energy makes us able to survive starving in weeks. TAG accumulate predominantly in adipocyte cytoplasm. There are more types of fatty acid oxidation. Individual types can be distinguished by different Greek letters. Greek letter denote atom in the fatty acid chain where reactions take place. β-oxidation is of major importance, it is localised in mitochondrial matrix. ω- and α- oxidation are localised in endoplasmic reticulum. Animal cells cannot convert fatty acids to glucose. Gluconeogenesis requires besides other things (1) energy, (2) carbon residues. Fatty acids are rich source of energy but they are not source of carbon residues (there is however one important exception, i.e. odd-numbered fatty acids). This is because cells are not able to convert AcCoA to neither pyruvate, nor OAA. Both carbons are split away as CO2. PDH is irreversible. Plant cells are capable of conversion of AcCoA to OAA in glyoxylate cycle. _ Lipids as source of energy – degradation of TAG in cells, β-oxidation of fatty acids Lipids are used for energy production, this process take place in 3 phases: 1) Lipid mobilisation – hydrolysis of TAG to FA and glycerol. FA and glycerol are transported Continue reading >>
Effects Of Exogenous Ketone Supplementation On Blood Ketone, Glucose, Triglyceride, And Lipoprotein Levels In Sprague–dawley Rats
Abstract Nutritional ketosis induced by the ketogenic diet (KD) has therapeutic applications for many disease states. We hypothesized that oral administration of exogenous ketone supplements could produce sustained nutritional ketosis (>0.5 mM) without carbohydrate restriction. We tested the effects of 28-day administration of five ketone supplements on blood glucose, ketones, and lipids in male Sprague–Dawley rats. The supplements included: 1,3-butanediol (BD), a sodium/potassium β-hydroxybutyrate (βHB) mineral salt (BMS), medium chain triglyceride oil (MCT), BMS + MCT 1:1 mixture, and 1,3 butanediol acetoacetate diester (KE). Rats received a daily 5–10 g/kg dose of their respective ketone supplement via intragastric gavage during treatment. Weekly whole blood samples were taken for analysis of glucose and βHB at baseline and, 0.5, 1, 4, 8, and 12 h post-gavage, or until βHB returned to baseline. At 28 days, triglycerides, total cholesterol and high-density lipoprotein (HDL) were measured. Exogenous ketone supplementation caused a rapid and sustained elevation of βHB, reduction of glucose, and little change to lipid biomarkers compared to control animals. This study demonstrates the efficacy and tolerability of oral exogenous ketone supplementation in inducing nutritional ketosis independent of dietary restriction. Background Emerging evidence supports the therapeutic potential of the ketogenic diet (KD) for a variety of disease states, leading investigators to research methods of harnessing the benefits of nutritional ketosis without the dietary restrictions. The KD has been used as an effective non-pharmacological therapy for pediatric intractable seizures since the 1920s [1–3]. In addition to epilepsy, the ketogenic diet has elicited significant therapeut Continue reading >>
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Biochemistry 10: Lipid Metabolism
These are notes from lecture 10 of Harvard Extension’s biochemistry class. intake and distribution of fats Fat can be consumed directly in the diet or derived (by the liver) from excess dietary carbohydrates. Once stored, it can be re-mobilized from adipose tissue. Typical humans (in developed countries??) get ~40% of their calories from dietary fat. Triacylglycerols (TAGs) are broken down by lipases. Pancreatic lipases in the intestinal lumen help to absorb fatty acids from the diet into the intestine. Lipoprotein lipases in the capillary walls help absorb fatty acid from chylomicrons and VLDLs into target tissues. Hormone-sensitive lipases inside cells break down fat stores in adipose tissue. Bile salts are various derivatives of cholesterol with different R2 groups at the end of the chain. The bile salt acts as a detergent, breaking apart large dietary globules of fat to yield smaller micelles, which are more accessible to lipases than the large globules. Intestinal lipases then convert TAGs into mono- and di-acylglycerols, free fatty acids, and glycerol. Now the TAGs need to somehow travel through the blood to be of use as energy to other organs. This is accomplished by packaging them into lipoproteins. A lipoprotein is a ball with a single-layered phospholipid + cholesterol surface, filled with triacylglycerols and cholesterol esters (cholesterol with a fatty acid attached). Apolipoproteins are embedded in the surface. class abbreviation density protein lipid content chylomicrons CM lowest lowest highest very low density lipoproteins VLDL .. .. .. intermediate density lipoproteins* IDL .. .. .. low density lipoproteins LDL .. .. .. high density lipoproteins HDL highest highest lowest *Yes, this is not a mistake; IDL is really in between VLDL and LDL, not between Continue reading >>
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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 >>
Preferential Utilization Of Ketone Bodies For The Synthesis Of Myelin Cholesterol In Vivo.
Abstract 1. The distribution of radioactivity among lipid classes of myelin and other subcellular brain fractions of young rats (18-21 days) was determined after in vivo injection of (3-(14)C-labelled ketone bodies, [U-(14)C] glucose or [2-(14)C] glucose. 2. The incorporation ratios (sterol/fatty acids) were 0.67, 1.48, 0.25, 0.62 and 0.54 for whole brain, myelin, mitochondria, microsomes and synaptosomes, respectively, with (3-(14)C)-labelled ketone bodies as substrate and 0.37, 0.89, 0.19, 0.34 and 0.29 with [U-(14)C] glucose as substrate. These data show that, both in whole brain and in subcellular brain fractions, acetyl groups derived from ketone bodies are used for sterol synthesis to a large extent than acetyl groups originating from glucose. 3. The specific radioactivity of cholesterol is much higher in myelin than in whole brain or in the other brain fractions, particularly after administration of labelled ketone bodies as substrate. 4. The incorporation patterns of acetoacetate and D-3-hydroxybutyrate were very similar, indicating that both ketone bodies contribute acetyl groups for lipid synthesis via the same metabolic route. 5. Our data suggest that a direct metabolic path from ketone bodies towards cholesterol exists - possibly via acetoacetyl-CoA formation in the cytosol of brain cells - and that this process is most active in oligodendrocytes. Continue reading >>
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What Is Ketosis Diet And What Does It Contain?
A keto diet is well known for being a low carb diet, where the body produces ketones in the liver to be used as energy. It’s referred to as many different names – ketogenic diet, low carb diet, low carb high fat (LCHF), etc. When you eat something high in carbs, your body will produce glucose and insulin. Glucose is the easiest molecule for your body to convert and use as energy, so it will be chosen over any other energy source. Insulin is produced to process the glucose in your bloodsteam, by taking it around the body. Since the glucose is being used as a primary energy, your fats are not needed, and are therefore stored. Typically on a normal, higher carbohydrate diet, the body will use glucose as the main form of energy. By lowering the intake of carbs, the body is induced into a state known as ketosis. Ketosis is a natural process the body initiates to help us survive when food intake is low. During this state, we produce ketones, which are produced from the breakdown of fats in the liver. The end goal of a properly maintained keto diet is to force your body into this metabolic state. We don’t do this through starvation of calories, but through starvation of carbohydrates. Our bodies are extremely adaptive to what you put into it – when you overload it with fats and take away carbohydrates, it will begin to burn ketones as the main energy source. Cholesterol. A keto diet has shown to improve triglyceride levels and cholesterol levels most associated with arterial buildup. Weight Loss. As your body is burning fat as the main source of energy, you will essentially be using your fat stores as an energy source while in a fasting state. Blood Sugar. Many studies show the decrease of LDL cholesterol over time and have shown to eliminate ailments such as type 2 di Continue reading >>
Triacylglycerols - Major Form Of Energy Storage In Animals
Lipid Metabolism Remember fats?? Your energy reserves: ~0.5% carbs (glycogen + glucose) ~15% protein (muscle, last resort) ~85% fat Why use fat for energy? 1 gram fat = at least 6-fold more energy than 1 gram carb Sources of fat: 1. Diet 2. Stored fat (adipose tissue) 3. Fat synthesized in one organ for export to another (excess carb converted to fat) Lipid Metabolism Hormones trigger mobilization of stored triacylglycerols Also heart, renal cortex Epinephrine, glucagon Lipid Metabolism How are fatty acids burned for energy? 1. Transported to mitochondria 2. Oxidized to produce acetyl CoA, NADH, FADH2 3. Acetyl CoA goes to citric acid cycle NADH, FADH2 donate e- to oxidative phos Lipid Metabolism Oxidation of fatty acids - fatty acid breakdown Transport of fatty acids into mitochondria â€œPrimeâ€ fatty acid Drives reaction Lipid Metabolism Oxidation of fatty acids - fatty acid breakdown Transport into mitochondria using carnitine intermediate Carnitine recycled Cytosolic and mitochondrial CoA pools stay balanced (CoAmatrix used for ox degrad of pyruvate, fatty acids, amino acids) (CoAcytosol used for fatty acid biosynthesis) Lipid Metabolism Oxidation of fatty acids - fatty acid breakdown b-oxidation of fatty acids (even # carbons) oxidized reduced Donates 2e- to Q (ox phos) oxidation hydration oxidation thiolysis Citric acid cycle Fatty acid shortened by 2 carbon atoms, cycle through b-oxidation again Oxidation of fatty acids - fatty acid breakdown b-oxidation of fatty acids (odd # carbons) b-oxidation gives a 3 carbon remnant Need ATP to put CO2 on biotin (Citric acid cycle intermediate) Lipid Metabolism Oxidation of fatty acids - regulation Need to regulate so oxidation only occurs when the need for energy requires it 1. Rate-limiting rxn. - fatty acids enteri Continue reading >>
Replacing The Cholesterol Hydroxyl Group With The Ketone Group Facilitates Sterol Flip-flop And Promotes Membrane Fluidity
Abstract The 3α-hydroxyl group is a characteristic structural element of all membrane sterol molecules, while the 3-ketone group is more typically found in steroid hormones. In this work, we investigate the effect of substituting the hydroxyl group in cholesterol with the ketone group to produce ketosterone. Extensive atomistic molecular dynamics simulations of saturated lipid membranes with either cholesterol or ketosterone show that, like cholesterol, ketosterone increases membrane order and induces condensation. However, the effect of ketosterone on membrane properties is considerably weaker than that of cholesterol. This is largely due to the unstable positioning of ketosterone at the membrane−water interface, which gives rise to a small but significant number of flip-flop transitions, where ketosterone is exchanged between membrane leaflets. This is remarkable, as flip-flop motions of sterol molecules have not been previously reported in analogous lipid bilayer simulations. In the same context, ketosterone is found to be more tilted with respect to the membrane normal than cholesterol. The atomic level mechanism responsible for the increase of the steroid tilt and the promotion of flip-flops is the decrease in polar interactions at the membrane−water interface. Interactions between lipids or water and the ketone group are found to be weaker than in the case of the hydroxyl group, which allows ketosterone to penetrate through the hydrocarbon region of a membrane. Department of Physical Chemistry, Barcelona University, c/ Marti i Franques 1, Pta 4, 08028 Barcelona, Spain, Department of Physics, Tampere University of Technology, Tampere, Finland, Department of Applied Mathematics, The University of Western Ontario, London (ON), Canada, Department of Applied Physi Continue reading >>
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 >>
How Can I Lose Weight As A Diabetic Who Hates Veggies?
Many veggies are high in carbohydrates, so while many vegetables provide a lot of the micronutrients (vitamins & minerals) you need, you don’t need to eat a diet that is primarily full of veggies to lose weight. The best kind of balanced diet is one that has the optimum ratios of macronutrients: fat, protein, and carbohydrates. There has been a great deal of debate in recent years on what those ratios should be, and it does vary from person to person. However, research is showing that what we were led to believe in the past, that eating fat makes you fat, is dead wrong. Eating a diet high in fat, moderate in protein, and very low in carbohydrates, such as the ketogenic diet (or commonly known as “keto”), puts your body into a state of ketosis, a natural metabolic state in which your body is no longer using glucose as its main source of fuel, and instead it begins using ketones to get its energy. Ketones are produced when your body is burning fat because no glucose is available. It is important not to confuse ketosis, a completely harmless and normal metabolic state, with ketoacidosis, a dangerous condition that occurs mostly in type 1 diabetics when they create high levels of both glucose and ketones at the same time. On the ketogenic plan, blood glucose usually drops, so this is not a danger for most people. However, if you are a type 1 diabetic, check with your doctor before switching to the ketogenic way of eating. So being in ketosis simply means that you have switched from being a sugar-burner to a fat-burner. Ketones are created when you are metabolizing fat, whether it is from the fat in the foods you eat or from the fat around your belly. The ketogenic diet also is an anti-inflammatory way of eating. Chronic inflammation has been shown to be a significant Continue reading >>