The Ketogenic Diet And Brain Metabolism Of Amino Acids: Relationship To The Anticonvulsant Effect
The Ketogenic Diet and Brain Metabolism of Amino Acids: Relationship to the Anticonvulsant Effect 1Childrens Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 1Childrens Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 1Childrens Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 1Childrens Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 1Childrens Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 2Department of Neuroscience, Norwegian University of Science and Technology, NTNU, N-7489, Trondheim, Norway The publisher's final edited version of this article is available at Annu Rev Nutr See other articles in PMC that cite the published article. In many epileptic patients, anticonvulsant drugs either fail adequately to control seizures or they cause serious side effects. An important adjunct to pharmacologic therapy is the ketogenic diet, which often improves seizure control, even in patients who respond poorly to medications. The mechanisms that explain the therapeutic effect are incompletely understood. Evidence points to an effect on brain handling of amino acids, especially glutamic acid, the major excitatory neurotransmitter of the central nervous system. The diet may limit the availability of oxaloacetate to the aspartate aminotransferase reaction, an important route of brain glutamate handling. As a result, more glutamate becomes accessible to the glutamate decarboxylase rea Continue reading >>
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- The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus
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What Is Gluconeogenesis?
Eat fat burn fat. Eat carbs burn carbs. It’s that simple, right? Yes and no. There’s more to it. Your body has many different metabolic pathways that it uses to provide energy for your cells. Glycolysis (using sugar for fuel) and lipolysis (using fat for fuel through beta-oxidation) are the most well-known metabolic pathways, but there are many more. One pathway, in particular, can turn the amino acids from protein into fuel. Why does it matter? Because this may be the one thing that is holding you back from getting into ketosis and losing fat while you are on a ketogenic diet. Gluconeogenesis — Your Liver’s “Magic Trick” If you are under some form stress or consume excess protein, your liver will perform a magic trick called gluconeogenesis. This literally translates to “the making of (genesis) new (neo) sugar (gluco)”. During gluconeogenesis, the liver (and occasionally the kidneys) turns non-sugar compounds like amino acids (the building blocks of protein), lactate, and glycerol into sugar that the body uses a fuel. When glycogen (your body’s sugar storage) is low, protein intake is high, or the body is under stress, amino acids from your meals and your muscle become one of your main energy sources. If your body continues to convert amino acids into fuel, it can keep you from getting into ketosis. This is why some ketogenic dieters may experience an increase in body fat percentage and a decrease in muscle mass during their first couple weeks on the ketogenic diet. But there is no need to worry. The ketogenic diet will still help reverse common health issues like diabetes and obesity and improve health in many ways. When you start the diet, however, gluconeogenesis will get in the way. One of the Problems With Going Ketogenic During the first three d Continue reading >>
Gluconeogenesis
Glucose is a key metabolite in human metabolism, but it is not always available at sufficient levels in the diet. Therefore, a pathway exists that converts other foodstuffs into glucose. This pathway is called gluconeogenesis. 7.1.1 Glucose is an indispensable metabolite The brain requires at least ~50% of its calories in the form of glucose Red blood cells exclusively subsist on glucose Glucose is a precursor of other sugars needed in the biosynthesis of nucleotides, glycoproteins, and glycolipids Glucose is needed to replenish NADPH, which supplies reducing power for biosynthesis and detoxification These considerations make the need for gluconeogenesis quite clear—we can’t just leave the blood glucose level up to the vagaries of dietary supply. Gluconeogenesis is the reversal of glycolysis, with several workarounds for the irreversible reactions in that pathway. In this scheme, the reactions that are shared between glycolysis and gluconeogenesis are shown in blue, whereas reactions that are specific for gluconeogenesis are shown in red. As you can see, both pyruvate and oxaloacetate are starting points for red arrows; therefore, any pathway that yields either of these, or indeed any other intermediate of glycolysis, can supply substrate carbon for gluconeogenesis. These pathways are indicated here by green arrows. The major substrate supply for gluconeogenesis is protein, both dietary and endogenous. Protein is first broken down into its constituent amino acids. Those amino acids that can be converted to pyruvate or any of the TCA cycle intermediates can serve as substrates for gluconeogenesis, and are therefore called glucogenic. Leucine, lysine and the aromatic amino acids are degraded to acetyl-CoA or acetoacetate. Since acetoacetate is a ketone body, and acety Continue reading >>
Glucogenic Amino Acids | The Biochemistry Questions Site
A free Biochemistry Question Bank for premed, medical students and FMG Answer to Biochemistry Question AM-02 about Amino acid Metabolism. Answer: (b) Ketogenic (Since the question only make reference to acetoacetyl CoA, we assume that it is the final product of the catabolism of this amino acid and no glucogenic metabolites are produced.) Amino acids are used for different purposes in our body. Most of the metabolic pool of amino acids is used as building blocks of proteins, and a smaller proportion is used to synthesize specialized nitrogenated molecules as epinephrine and norepinephrine, neurotransmitters and the precursors of purines and pyrimidines. Since amino acids can not be stored in the body for later use, any amino acid not required for immediate biosynthetic needs is deaminated and the carbon skeletonis used as metabolic fuel (10-20 % in normal conditions) or converted into fatty acids via acetyl CoA. The main products of the catabolism of the carbon skeleton of the amino acids are pyruvate, oxalacetate, a-ketoglutarate, succinyl CoA, fumarate, acetyl CoA and acetoacetyl CoA. When carbohydrates are not available (starvation, fasting) -or cannot be used properly, as in diabetes mellitus, amino acids can become a primary source of energy by oxidation of their carbon skeleton, but also by becoming an important source of glucose for those tissues that only can use this sugar as metabolic fuel. The formation of glucose from amino acids (gluconeogenesis) in liver and kidney is intensified during starvation and this process becomes the most important source of glucose for the brain, RBC and other tissues. Amino acids in skeletal proteins can be used, in a situation of prolonged starvation as an emergency energy store that can yield 25000 kcal. Amino acids can be cl Continue reading >>
Protein Metabolism - Welcome To Bio Stud...
The figure above show the overall summary of metabolism, in this site we will only discuss about proteins (amino acids) metabolism. obtained from essential or normal protein break down. Ketogenic & glucogenic amino acids (energy) Proteins degraded when the body's energy source are low and being used as an alternative energy source. Called as ketogenic and glucogenic. When energy sources are high, both ketogenic and glucogenic amino acids are ocnverted to fatty acids through the intermediate acetyl CoA. ketogenic amino acids can produce ketones when energy sources are low. degraded directly to ketone bodies such as acetoacetate (acetyl CoA). acetoacetate can be metabolized by the brain and muscle for energy when blood glucose is low. acetoacetate cannot be used in gluconeogenesis since acetyl CoA cannot be converted directly to oxaloacetate (OAA). glucogenic amino acids can be degraded to pyruvate or an intermediate in the Krebs Cycle. can produce glucose under certain conditions of low glucose. also called gluconeogenesis/ production of glucose from pyruvate or other intermediate in the Krebs Cycle. release energy that later being used in anabolism Continue reading >>
Nutr 251 Exam 2 Review (minus Lipids)
Briefly outline the process of digestion and absorption of beef protein. 2) Stomach-HCL denature proteins, pepsin is activated to further break down proteins to smaller polypeptides 3) Small intestine-90% of digestion of proteins occurs here, pancreatic/enzymes break polypeptides down further to amino acids 4) Absorbed by active transport, travels to the portal vein and then to the liver 4 functions of essential amino acids other than protein synthesis 1) Act as precursors (ex- tryptophan can be converted to serotonin) 2) Used for fuel, but to lesser degree than fatty acids and glucose 3) Converted to fatty acids and put into fat cell storage when energy in is greater than energy out (there is too much protein being converted to fat) 4) Carbon portion can be converted to glucose in a process called gluconeogenesis which happens in starvation Chemical structure of protein vs. complex carbohydrates -A protein is made of long chains of amino acids linked together by peptide bonds -Complex carbohydrates are made of glucose units in straight or branched chains How is the chemical structure of a monosaccharide different from that of an amino acid? 1) Collagen- the framework for bone/teeth structures 2) Regulate fluid balance- R groups are charged and can attract water 6) Hormones (insulin and gastrin are protein hormones) What happens to the ammonia and urea as an end product of this process? Deamination- amino acids are stripped of their nitrogen containing amino groups, first step when amino acids are broken down [Products of deamination are ammonia and a keto acid (the carbon part of the amino acids)] Ammonia combines with CO2 and is excreted as urea How many essential amino acids are in the diet? Describe the sources of amino acids for the "amino acid pool." Why must thi Continue reading >>
Gluconeogenesis
Gluconeogenesis (GNG) is a metabolic process of making glucose, a necessary body fuel, from non-carbohydrate sources such as protein (amino acids), lactate from the muscles and the glycerol component of fatty acids. Blood glucose levels must be maintained within a narrow range for good health. If blood sugar is too high, it results in tissue and organ damage. If it is too low, cellular respiration and energy production can suffer, especially if the body is "carbohydrate-adapted," meaning the body uses glucose as it's primary fuel. Therefore, the ability of the liver and kidneys to “make new sugar” and regulate blood sugar levels is critical. The main advantage of this process is that it helps the body maintain steady blood sugar levels when foods containing carbohydrates or stored sugars (glycogen reserves) are unavailable. Without gluconeogenesis, you wouldn't live very long, especially without food, as your body must have a constant and steady level of blood glucose to keep the brain and red blood cells going. Mold Test Kits Easy to Use, Fast Results Available Interpretive Lab Report moldtesting.com Glucose and Ignorance If you decide to stop eating, or you decide to follow a low carb ketogenic diet, carbohydrate intake drops. To make up for the missing carbohydrate in your diet, the liver creates the blood glucose it needs by breaking down the glycogen stored in your muscles and liver from your last meal. This process is called glycogenolysis. After about 30 hours with no food, a great deal of this stored glycogen is broken down, and the body must then begin making glucose by breaking down stored fatty acids or amino acids from the protein in your muscles. Some dietitians and trainers insist that this process is the reason that carbohydrates are "essential foods" Continue reading >>
Ketogenesis
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.[1][2] 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.[3] Production[edit] 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.[3] Other cells are capable of carrying out ketogenesis, but they are not as effective at doing so.[4] Ketogenesis occurs constantly in a healthy individual.[5] Ketogenesis takes place in the setting of low glucose levels in the blood, after exhaustion of other cellular carbohydrate stores, such as glycogen.[citation needed] 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.[3] 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 >>
Glucogenic Vs Ketogenic Amino Acids | Optimising Nutrition
While a lot of attention is often given to macronutrient balance, quantifying the vitamin and mineral sufficiency of our diet is typically done by guesswork. This article lists the foods that are highest in amino acids, vitamins, minerals or omega 3 refined to suit people with different goals (e.g. diabetes management, weight loss, therapeutic ketosis or a metabolically healthy athlete). Ive spent some time lately analysing peoples food diaries, noting nutritional deficiencies, and suggesting specific foods to fill nutritional gaps while still being mindful of the capacity of the individual to process glucose based on their individual insulin sensitivity and pancreatic function. The output from nutritiondata.self.com below shows an example of the nutrient balance and protein quality analysis. In this instance the meal has plenty of protein but is lacking in vitamins and minerals, which is not uncommon for people who are trying to reduce their carbohydrates to minimise their blood glucose levels. The pink spokes of the nutrient balance plot on the left shows the vitamins while the white shows the minerals. On the right hand side the individual spokes of the protein quality score represent individual amino acids. A score of 100 means that you will meet the recommended daily intake (RDI) for all the nutrients with 1000 calories, so a score of 40 in the nutrient balance as shown is less than desirable if we are trying to maximise nutrition. [1] I thought it would be useful to develop a shortlist of foods to enable people to find foods with high levels of particular nutrients to fill in possible deficiencies while being mindful of their ability to deal with glucose. The list of essential nutrients below is the basis of the nutrient density scoring system used in the Your Pe Continue reading >>
Amino Acid Metabolism
Amino acids are categorized into two types - non-essential amino acids (can be synthesized by the body) and essential amino acids which cannot, and have to be provided from the diet. The non-essential amino acids are glycine, alanine, serine, asparagine, aspartic acid, glutamine, glutamic acid, proline, cysteine, tyrosine and arginine. The essential amino acids include valine, leucine, isoleucine, phenylalanine, tryptophan, methionine, threonine, lysine and histidine. The amino acids arginine, methionine and phenylalanine are considered essential because their rate of synthesis is insufficient to meet the growth needs of the body. Most of synthesized arginine is cleaved to form urea. Methionine is required in large amounts to produce cysteine if the latter amino acid is not adequately supplied in the diet. Similarly, phenylalanine is needed in large amounts to form tyrosine if the latter is not adequately supplied in the diet. The amino acid pool comes from protein degradation in the gastro-intestinal tract, intracellular protein degradation and de novo synthesis and is used in protein synthesis and metabolism. Each amino acid type has its own metabolic fate and specific functions. Not only does this metabolic process generate energy, but it also generates key intermediates for the biosynthesis of certain non-essential amino acids, glucose and fat. Synthesis of non-essential amino acids Essential amino acids - valine, leucine, isoleucine, phenylalanine, tryptophan, methionine, threonine, lysine and histidine - cannot be synthesized by the human body and thus have to be provided from the diet. While the amino acids arginine, methionine and phenyalanine can be synthesized by mammalian cells they are considered dietary essentials as their rate of synthesis is insufficient Continue reading >>
Gluconeogenesis - Kansas State Hn 400 Human Nutrition
Gluconeogenesis: The opposite of glycolysis, using other products like amino acids to make glucose. Amino acid uptake go from the amino acids through the amino acid transporters into the hepatocyte. The anabolic pathway of amino acids leads to protein synthesis. The catabolic pathway of amino acids can lead to gluconeogenesis that assist the formation of glucose. As shown below gluconeogenesis is like glycolysis in reverse with an oxaloacetate workaround. Oxaloacetate is a TCA cycle intermediate that is formed instead of directly converting pyruvate to phosphoenolpyruvate, which would be glycolysis exactly in reverse. Oxaloacetate then is just what is formed as an intermediate between the two steps. This gluconeogenesis animation does a good job of illustrating and explaining gluconeogenesis. We can use amino acids in gluconeogenesis to make glucose, but we cannot use ALL amino acids. Fatty acids cannot be used to form glucose because it makes Acetyl-CoA. The transition reaction that forms acetyl CoA from pyruvate is a one way reaction. This means that Acetyl-CoA can't be used to form pyruvate. In othe words, we can not go back from Acetyl-CoA to pyruvate. This occurs in the liver & kidney to some extent. Glucose is exported to tissues. Pyruvate is decarboxylated - the carboxyl group (-COOH) is split forming carbon dioxide. It is dehydrogenated - elimination of hydrogren It is added to CoA to form Acetyl CoA - remember CoA is Coenzyme A, responsible for oxidizing pyruvate in the Citric Acid/Kreb's cycle Why can't Acetyl CoA be used to from glucose through the Kreb's cycle? Because the Acetyl CoA carbons are given off as CO2, there is no carbon skeleton left to be used for gluconeogenesis. Glycerol can be used, but it makes very little glucose. Shows where all the amino Continue reading >>
Why Can Fatty Acids Not Be Converted Into Glucose? : Mcat
Rudeness or trolling will not be tolerated. Be nice to each other, hating on other users won't help you get extra points on the MCAT, so why do it? Do not post any question information from any resource in the title of your post. These are considered spoilers and should be marked as such. For an example format for submitting pictures of questions from practice material click here Do not link to content that infringes on copyright laws (MCAT torrents, third party resources, etc). Do not post repeat "GOOD LUCK", "TEST SCORE", or test reaction posts. We have one "stickied" post for each exam and score release day, contain all test day discussion/reactions to that thread only. Do not discuss any specific information from your actual MCAT exam. You have signed an examinee agreement, and it will be enforced on this subreddit. Do not intentionally advertise paid products or services of any sort. These posts will be removed and the user banned without warning, subject to the discretion of the mod team Learn More All of the above rules are subject to moderator discretion C/P = Chemical and Physical Foundations of Biological Systems CARS = Critical Analysis and Reasoning Skills B/B = Biological and Biochemical Foundations of Living Systems P/S = Psychological, Social, and Biological Foundations of Behavior Continue reading >>
We Really Can Make Glucose From Fatty Acids After All! O Textbook, How Thy Biochemistry Hast Deceived Me!
Biochemistry textbooks generally tell us that we can’t turn fatty acids into glucose. For example, on page 634 of the 2006 and 2008 editions of Biochemistry by Berg, Tymoczko, and Stryer, we find the following: Animals Cannot Convert Fatty Acids to Glucose It is important to note that animals are unable to effect the net synthesis of glucose from fatty acids. Specficially, acetyl CoA cannot be converted into pyruvate or oxaloacetate in animals. In fact this is so important that it should be written in italics and have its own bold heading! But it’s not quite right. Making glucose from fatty acids is low-paying work. It’s not the type of alchemy that would allow us to build imperial palaces out of sugar cubes or offer hourly sweet sacrifices upon the altar of the glorious god of glucose (God forbid!). But it can be done, and it’ll help pay the bills when times are tight. All Aboard the Acetyl CoA! When we’re running primarily on fatty acids, our livers break the bulk of these fatty acids down into two-carbon units called acetate. When acetate hangs out all by its lonesome like it does in a bottle of vinegar, it’s called acetic acid and it gives vinegar its characteristic smell. Our livers aren’t bottles of vinegar, however, and they do things a bit differently. They have a little shuttle called coenzyme A, or “CoA” for short, that carries acetate wherever it needs to go. When the acetate passenger is loaded onto the CoA shuttle, we refer to the whole shebang as acetyl CoA. As acetyl CoA moves its caboose along the biochemical railway, it eventually reaches a crossroads where it has to decide whether to enter the Land of Ketogenesis or traverse the TCA cycle. The Land of Ketogenesis is a quite magical place to which we’ll return in a few moments, but n Continue reading >>
- International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #82: Insulin Actions In Vivo: Glucose Metabolism Part 9 of 9
- World's first diabetes app will be able to check glucose levels without drawing a drop of blood and will be able to reveal what a can of coke REALLY does to sugar levels
- International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #59: Mechanisms of insulin signal transduction Part 3 of 8
Glucogenic And Ketogenic Amino Acids
Amino acids can be classified as being “glucogenic” or “ketogenic” based on the type of intermediates that are formed during their breakdown or catabolism. The catabolism of glucogenic amino acids produces either pyruvate or one of the intermediates in the Krebs Cycle. The catabolism of ketogenic amino acids produces acetyl CoA or acetoacetyl CoA (see Figure 1). There is a rare medical condition in which a person is deficient in the pyruvate dehydrogenase enzyme that converts pyruvate to acetyl CoA – a precursor for the Krebs Cycle. Signs and symptoms vary, but there are generally two main manifestations. First, patients can have an elevated blood lactate (lactic acid) level. Second, patients may have neurological defects, including microcephaly (a small head circumference) and/or mental retardation. Treatment is currently limited and not very effective. Moreover, damage to the brain is often irreversible. Your biochemistry study partner looks at Figure 1 and exclaims, “This doesn’t make sense - why can’t acetyl-coA and the ketogenic amino acids be converted back to pyruvate to create glucose using pyruvate dehydrogenase?” With your knowledge of basic chemistry, you answer: Continue reading >>
Gluconeogenesis – The Worst Name For A Rock Band Ever
At least three times a week I am engaged either in the Facebook group or other places asking questions that generally go like this: “At what point do I eat too much protein and go into gluconeogenesis ?” So I wanted to provide a more thought out answer, so here goes. I should add that my commentary here is largely to be filtered through the lens of T1 diabetes…if you’re T1 diabetic, the regulatory feedback mechanisms are endogenously broken (the pancreas isn’t producing insulin), and must be regulated exogenously (the injection of insulin). What is gluconeogenesis? Gluconeogenesis (also known as GNG) is the process by which the body takes “stuff” that isn’t glucose (the more technical term is “non-glucose substrate”) and turns it into glucose. It is an ongoing process which happens in complete starvation as well as in a modified starvation or even a fully fed state. Translation – gluconeogenesis happens all the time, in everyone, everywhere. It seems to happen at a relatively consistent rate. I will get into some additional details on that rate later, but for now, the message is this – studies which have been conducted on humans are lacking, but those which have been done have shown that the rate of GNG does not materially change when protein content of the diet is manipulated. Often, GNG is spoken of as “too much protein in my diet causes it to turn into glucose,” or glibly said…“protein turning into chocolate cake.” The biochemical reality is, however, that it is a bit more complex than that. There are essentially three major contributors to gluconeogenesis which warrant discussion. Protein Protein is composed of amino acids linked together. Some amino acids are called “ketogenic” which (for the purposes of our talk) means that th Continue reading >>
