diabetestalk.net

Where Are Ketone Bodies Broken Down?

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 Bodies

Ketone Bodies

Introductory discusion of fat metabolism, exercise, and fasting. Fatty acids can be used as the major fuel for tissues such as muscle, but they cannot cross the blood-brain barrier, and thus cannot be used by the central nervous system (CNS). This becomes a major problem during starvation (fasting), particularly for organisms such as ourselves in which CNS metabolism constitute a major portion of the resting basal metabolic rate. These organism must provide glucose to the CNS to provide for metabolic needs, and thus during the initial fasting period must break down substantial amounts of muscle tissue (protein) to provide the amino acid precursors of gluconeogenesis. Obviously the organism could not survive long under such a regime. What is needed is an alternate fuel source based on fat rather than muscle. The so-called ketone bodies serve this function: Note that only two of the ketone bodies are in fact ketones, and that acetone is an "unintentional" breakdown product resulting from the instability of acetoacetate at body temperature. Acetone is not available as fuel to any significant extent, and is thus a waste product. CNS tissues can use ketone bodies any time, the problem is the normally very low concentrations (< 0.3 mM) compared to glucose (about 4 mM). Since the KM's for both are similar, the CNS doesn't begin to use ketone bodies in preference to glucose until their concentration exceed's the concentration of glucose in the serum. The system becomes saturated at about 7 mM. The limiting factor in using ketone bodies then becomes the ability of the liver to synthesis them, which requires the induction of the enzymes required for acetoacetate biosynthesis. Normal glucose concentrations inhibit ketone body synthesis, thus the ketone bodies will only begin to be Continue reading >>

Regulation Of Ketone Body Metabolism And The Role Of Pparα

Regulation Of Ketone Body Metabolism And The Role Of Pparα

1. Introduction Adaptation to limited nutritional resources in the environment requires the development of mechanisms that enable temporal functioning in a state of energy deficiency at both systemic and cellular levels. Different molecular and cellular mechanisms have evolved allowing survival during nutrient insufficiency. Some rely on the decrease of metabolic rates, body temperature, or even shutting down most of the live functions during deep hibernation, aestivation or brumation. Other strategies require development of metabolic flexibility and effective fuel management. Peroxisome Proliferator Activated Receptors (PPARs) are important regulators of cellular responses to variable nutrient supply during both fed and fasted states. Acting as transcription factors, and directly modulated by fatty acids and their derivatives, PPARs induce transcription of the proper set of genes, encoding proteins and enzymes indispensable for lipid, amino acid and carbohydrate metabolism. In this review, we make an attempt to outline the regulation of ketone body synthesis and utilization in normal and transformed cells, as well as summarize the role of PPARα in these processes. 2. Ketogenesis and Ketolysis Metabolic adaptation to prolonged fasting in humans is based both on coordinated responses of vital organs, mainly liver, kidneys and muscles, and on restoring nutritional preferences at the cellular level. In the fed state, cells primarily rely on glucose metabolism, whereas during longer food deprivation blood glucose levels drop because glycogen reserves are only sufficient for less than a day. In such conditions, glucose is spared mainly for neurons, but also for erythrocytes and proliferating cells in bone marrow or those involved in tissue regeneration. The most important c Continue reading >>

Ketosis, Ketones, And How It All Works

Ketosis, Ketones, And How It All Works

Ketosis is a process that the body does on an everyday basis, regardless of the number of carbs you eat. Your body adapts to what is put in it, processing different types of nutrients into the fuels that it needs. Proteins, fats, and carbs can all be processed for use. Eating a low carb, high fat diet just ramps up this process, which is a normal and safe chemical reaction. When you eat carbohydrate based foods or excess amounts of protein, your body will break this down into sugar – known as glucose. Why? Glucose is needed in the creation of ATP (an energy molecule), which is a fuel that is needed for the daily activities and maintenance inside our bodies. If you’ve ever used our keto calculator to determine your caloric needs, you will see that your body uses up quite a lot of calories. It’s true, our bodies use up much of the nutrients we intake just to maintain itself on a daily basis. If you eat enough food, there will likely be an excess of glucose that your body doesn’t need. There are two main things that happen to excess glucose if your body doesn’t need it: Glycogenesis. Excess glucose will be converted to glycogen and stored in your liver and muscles. Estimates show that only about half of your daily energy can be stored as glycogen. Lipogenesis. If there’s already enough glycogen in your muscles and liver, any extra glucose will be converted into fats and stored. So, what happens to you once your body has no more glucose or glycogen? Ketosis happens. When your body has no access to food, like when you are sleeping or when you are on a ketogenic diet, the body will burn fat and create molecules called ketones. We can thank our body’s ability to switch metabolic pathways for that. These ketones are created when the body breaks down fats, creating Continue reading >>

How Does The Body Adapt To Starvation?

How Does The Body Adapt To Starvation?

- [Instructor] In this video, I want to explore the question of how does our body adapt to periods of prolonged starvation. So in order to answer this question, I actually think it's helpful to remind ourselves first of a golden rule of homeostasis inside of our body. So in order to survive, remember that our body must be able to maintain proper blood glucose levels. I'm gonna go ahead and write we must be able to maintain glucose levels in our blood, and this is important even in periods of prolonged starvation, because it turns out that we need to maintain glucose levels above a certain concentration in order to survive, even if that concentration is lower than normal. And this of course brings up the question, well, how does our body maintain blood glucose levels? So let's go ahead and answer this question by starting off small. Let's say we have a mini case of starvation, let's say three or four hours after a meal. Your blood glucose levels begin to drop, and so what does your body do to resolve that? Well, at this point, it has a quick and easy solution. It turns to its glycogen stores in the liver. Remember that our body stores up these strings of glucose inside of our body so that we can easily pump it back into the blood when we're not eating. But unfortunately humans only have enough glycogen stores to last us about a day, so after a day of starvation, our body's pretty much reliant exclusively on the metabolic pathways involved in gluconeogenesis, which if you remember is the pathway by which we produce new or neo glucose. And we produce this glucose from non-carbohydrate precursor molecules. So let's think about what else we have in our body. Remember that our other two major storage fuels are fats, and we usually think about fatty acids containing most of th Continue reading >>

Ketone Metabolism

Ketone Metabolism

Under conditions of abundant glucose (and sufficient insulin sensitivity) the brain is primarily converting glucose to pyruvate that is then shuttled into the mitochondria and converted into acetyl CoA. Acetyl CoA (which is also a direct byproduct of fatty acid breakdown) is then combined with oxaloacetate and so begins the tricarboxylic acid cycle, which generates all the reducing agents to feed the electron transport chain and generate massive amounts of ATP. In the absence of acetyl CoA, to spare muscle fat and proteins, our liver can produce ketone bodies that are produced when fatty acids are broken down in excess. The two main ketone bodies are acetoacetate and β-hydroxybutyrate, the latter being produced from the former through the reversible enzymatic action of hydroxybutyrate dehydrogenase (BDH). Acetone, the third one, cannot be converted back to acetyl-CoA, so it is excreted in the urine and exhaled, contributing to the characteristic “fruity” odor of the breath of patients in ketotic states. Production of these compounds is called “ketogenesis”, a process that is necessary in small amounts as source of fuel for brain, heart and muscle. They become the major energy source (about 75%) for brain during starvation. When excess ketone bodies accumulate, this abnormal (but not necessarily harmful) state is called ketosis. When even larger amounts of ketone bodies accumulate such that the body’s pH is lowered to dangerously acidic levels, this state is called ketoacidosis. Continue reading >>

The Stanbio Chemistry Beta-hydroxybutyrate Liquicolor® Reagent

The Stanbio Chemistry Beta-hydroxybutyrate Liquicolor® Reagent

Diabetic ketoacidosis is a problem that occurs in people with diabetes. It occurs when the body cannot use sugar (glucose) as a fuel source because there is no insulin or not enough insulin, and fat is used for fuel instead. Other symptoms include: Abdominal pain Breathing difficulty while lying down Decreased appetite Decreased consciousness Dulled senses that may worsen to a coma Fatigue Frequent urination or thirst that lasts for a day or more Headache Muscle stiffness or aches Shortness of breath People with type 1 diabetes may be at risk when they do not have enough insulin, a hormone the body uses to break down sugar (glucose) in the blood for energy. When the body senses glucose is not available, fat is broken down instead. As fats are broken down, acids called ketones build up in the blood and urine. Ketones are poisonous in high levels and this condition is called ketoacidosis. Blood glucose levels rise (usually higher than 300 mg/dL) because the liver makes glucose to try to combat the problem. However the cells cannot pull in that glucose without insulin. Diabetic ketoacidosis may be the first sign of type 1 diabetes in people who do not yet have other symptoms. It can also occur in someone who has already been diagnosed with type 1 diabetes. Infection, injury, a serious illness, or surgery can lead to diabetic ketoacidosis in people with type 1 diabetes. Ketoacidosis can also occur in people with diabetes when they miss their insulin treatments. People with type 2 diabetes can develop ketoacidosis, but it is rare. It is usually triggered by a severe illness. Hispanic and African-American people are more likely to have ketoacidosis as a complication of type 2 diabetes. During ketosis, Beta-Hydroxybutyrate (BHB) levels may increase more than levels of acetone 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 >>

Nutrition Ch. 7

Nutrition Ch. 7

Front Back .Wirisformula{ margin:0 !important; padding:0 !important; vertical-align:top !important;} Metabolism The sum total of all the chemcial reactions that go on in living cells. Energy metabolism includes all the reactions by which the body obtains and spends energy from food. Example: Nutrients provide the body with FUEL and follows them through a series of reactions that release energy from their chemical bonds. As the bonds break, they release energy in a controlled version of the process by which wood burns in a fire. Energy metabolism All of the chemical reactions through which the human body acquires and spends energy from food Anabolism Small compounds joined together to make largers ones; energy must be used in order to do this Ana = up Catabolism Larger compounds BROKEN down into smaller ones; energy is RELEASED kata = down Coupled reactions Energy released from the breakdown of a large compounds is used to drive other reactions ATP Adenosine triphosphate; energy currency of the body -- produced when large compounds are broken down ATP is used to make large compounds from smaller ones. Ribosomes Cellular machinery used to make proteins Mitochondria Where energy is derived from fat, CHO, protein via TCA cycle, electron transport chain Coenzyme Complex organic molecules that work with enzymes to facilitate the enzymes' activity. Many coenzymes have B vitamins as part of their structures. co = with Cofactor The general term for substances that facilitate enzyme action is cofactors; they include both organic coenzymes such as vitamins and inorganic substances such as minerals Enzymes Protein catalysts - proteins that facilitate chemical reactions without being changed in the process Metalloenzyme Enzymes that contain one or more minerals as part of their stru Continue reading >>

“ketone Bodies” A Trendy Word

“ketone Bodies” A Trendy Word

Health Writer Ketosis is a normal process where excessive ketone bodies formed, a crucial organic compound – acetoacetate, when human body is starved of carbohydrates for energy requirements. Plan B in the body under such strained situations would be to use fatty acids stored in the body as triglycerides to burn its own fat for fuel, for energy requirements in the liver, heart and kidneys, due to the restriction of energy from carbohydrates. The process of ketones production in humans is called ketogenesis. In the brain, they are a vital source of energy during fasting when the body is deprived of carbohydrates. Brain cells would prefer energy from sugars, being much more physiological. So, we have to understand that ketone body formation is a natural event under carbohydrate deprived situation (plan B). Ketosis presents a danger to some patients, having liver and kidney damage, and also type 1 diabetic. When people restrict their carbohydrate consumption, as in situations of starvation, lost in the jungle, or deliberate, the body turns to fat (Plan B), as an energy source. So as mentioned the fats are broken down to fatty acids to form chemicals – aceto-acetic, beta- hydroxyl-butyric acid and acetone. Same mechanism – production of excessive ketones can be activated by making people restrict their carbohydrates to very low levels and increasing the fat and protein consumption to a most un-physiological unnatural consumption situation. These are not balanced diets and a juggle with carbohydrates, proteins and fats. The late Dr Robert Atkins advocated this diet to slim, and many variations of this ketogenic diet appeared in the market, subsequently. The rationale involved here is that when carbohydrates are restricted the body turns to fat for energy requirements ( Continue reading >>

Biochemistry 12: Diabetes

Biochemistry 12: Diabetes

These are notes from lecture 12 of Harvard Extension’s biochemistry class. starvation The first priority is to provide enough glucose to tissues that are solely dependent on glucose – the brain and red blood cells. It was long thought that fatty acids cannot be converted to glucose, though there is now some evidence that this conversion may occur under some circumstances. Amino acids are a poor fuel source because they’re not stored (no equivalent of glycogen or triacylglycerol), so you’d just be catabolizing proteins you need to live. Starvation occurs in stages. Exogenous glucose can be used for the first 4 hours after a meal. Then glycogen reserves kick in from hour 4 to hour ~28. As the glycogen mobilization peaks around hour 8, gluconeogenesis begins, and can continue full steam for about 2 days, after which it dampens slightly but can continue for up to 40 days at a lower level. During days 2-24, the kidney begins gluconeogenesis and the brain begins using ketone bodies. In Stage V (days 24-40), the liver and kidney continue to do gluconeogenesis and the brain relies solely on ketone bodies. Muscle protein degradation is about 75 g/day at day 3 of starvation, 20 g/day at day 40 of starvation. The initial sources of proteins are rapid turnover proteins from the intestinal epithelium and secreted pancreatic proteins. After three days, the liver forms ketone bodies (from fatty acid catabolism) which become the predominant energy source, preventing additional protein degradation. After an average of 40 days (more if you have more adipose tissue), TAG stores are depleted, and protein degradation increases again, impacting heart, liver and kidney function and leading ultimately to death. See [Berg 2002] for an overview of all this, esp. muscle protein degradatio Continue reading >>

Ketosis Fundamentals

Ketosis Fundamentals

What is ketosis? Ketosis is the physiological state where the concentration of ketone bodies in the blood is higher than normal. This is generally agreed to be at beta-hydroxybutyrate (BHB) concentrations greater than 0.5 mM. How to achieve ketosis? Ketosis occurs either as a result of increased fat oxidation, whilst fasting or following a strict ketosis diet plan (ENDOGENOUS ketosis), or after consuming a ketone supplement (EXOGENOUS ketosis). When in a state of ketosis the body can use ketones to provide a fuel for cellular respiration instead of its usual substrates: carbohydrate, fat or protein. Why does ketosis exist? Normally, the body breaks down carbohydrates, fat, and (sometimes) proteins to provide energy. When carbohydrate is consumed in the diet, some is used immediately to maintain blood glucose levels, and the rest is stored. The hormone that signals to cells to store carbohydrate is insulin. The liver stores carbohydrate as glycogen, this is broken down and released between meals to keep blood glucose levels constant. Muscles also store glycogen, when broken down this provides fuel for exercise. Most cells in the body can switch readily between using carbohydrates and fat as fuel. Fuel used depends on substrate availability, on the energy demands of the cell and other neural and hormonal signals. The brain is different as it is dependent on carbohydrates as a fuel source. This is because fats cannot easily cross the blood-brain barrier. The inability to make use of energy within fat poses a problem during periods where there is limited carbohydrate in the diet. If blood glucose levels fall to low, brain function declines. Relatively little energy is stored as carbohydrate (2,000 kCal) compared to fat (150,000 kCal). The body's store of carbohydrates runs Continue reading >>

Ketone Body Neutralizes Harmful Metabolite Of Glucose Metabolism

Ketone Body Neutralizes Harmful Metabolite Of Glucose Metabolism

Ketone bodies (including acetoacetate, β-hydroxybutyrate and acetone) are produced mainly by the liver from fatty acids during fasting, prolonged physical activity, starvation, or ketogenic diets (diets that restrict carbohydrates to usually < 50 g/day). The metabolic state in which ketone bodies are utilized as the main energy source for the body instead of glucose is called ketosis. Physiological or nutritional ketosis has been shown to lead to several metabolic advantages including weight management and improvements in glycemic control and blood lipids [1]. A recent article, published in Cell Chemical Biology, demonstrates a new biological function of ketone bodies: neutralizing methylglyoxal (MG), a highly reactive metabolite of glucose metabolism known to be involved in aging- and diabetes-related diseases [2]. MG has been shown to react with and cause damage to DNA and proteins, forming advanced glycation end products (AGEs) that are linked to many aging-related pathologies [3]. Levels of MG are elevated in patients with type 2 diabetes (T2D) as well. An interdisciplinary team of researchers from Aarhus University (Aarhus, Denmark) found that, when ketosis was induced in diabetic patients, the generated ketone body acetoacetate efficiently reacted with MG in the blood and formed a new compound called 3-hydroxyhexane-2,5-dione (3-HHD). 3-HHD was then broken down to less-reactive species by the blood cells. The investigators then studied healthy individuals who were placed on a ketogenic diet, and found that the ketone body acetoacetate generated during nutritional ketosis also reacted with MG and formed 3-HHD. These observations suggest that acetoacetate is a MG scavenger during pathological conditions such as diabetic ketosis, as well as during nutritional ketosi Continue reading >>

Everything You Need To Know About Ketones

Everything You Need To Know About Ketones

Ketone is an organic compound that the body produces when fats are broken down for energy. People with diabetes may not be able to regulate the level of ketones in their blood, so ketone testing is an essential part of managing their condition. There are three types of ketone, which are collectively known as ketone bodies, or ketones. In this article, we explain when to check for ketones, the types of tests available, and how to understand the results. Contents of this article: What are ketones? The body uses a range of nutrients for energy, including carbohydrates, fats, and proteins. It will use carbohydrates first, but if none are available, the body will burn fat for energy. When this happens, ketones are produced. Ketones have gained attention in recent years due to the popularity of ketogenic diets, in which people eat a low carbohydrate diet so that their body will burn fat instead of carbohydrates. There is currently a lack of clear evidence on the benefits of this diet, and there may be some risks, such as high acidity in the blood and loss of muscle. Typically, carbohydrates are broken down into different nutrients, including blood sugar (glucose), by an enzyme called amylase that occurs naturally in the body. Insulin then transports the sugar to cells to be used for energy. A person with diabetes does not produce enough insulin to transport the blood sugar, or the cells in their body may not accept it properly, which stops the body from using the blood sugar for energy. When sugar can't be used by the cells for energy, the body will start to break down fats for energy instead. Types of ketone and DKA Three types of ketones are always present in the blood: acetoacetate (AcAc) 3-β-hydroxybutyrate (3HB) acetone The levels of each of these ketone bodies will var Continue reading >>

The Catabolism Of Fats And Proteins For Energy

The Catabolism Of Fats And Proteins For Energy

Before we get into anything, what does the word catabolism mean? When we went over catabolic and anabolic reactions, we said that catabolic reactions are the ones that break apart molecules. To remember what catabolic means, think of a CATastrophe where things are falling apart and breaking apart. You could also remember cats that tear apart your furniture. In order to make ATP for energy, the body breaks down mostly carbs, some fats and very small amounts of protein. Carbs are the go-to food, the favorite food that cells use to make ATP but now we’re going to see how our cells use fats and proteins for energy. What we’re going to find is that they are ALL going to be turned into sugars (acetyl) as this picture below shows. First let’s do a quick review of things you already know because it is assumed you learned cell respiration already and how glucose levels are regulated in your blood! Glucose can be stored as glycogen through a process known as glycogenesis. The hormone that promotes this process is insulin. Then when glycogen needs to be broken down, the hormone glucagon, promotes glycogenolysis (Glycogen-o-lysis) to break apart the glycogen and increase the blood sugar level. Glucose breaks down to form phosphoglycerate (PGAL) and then pyruvic acid. What do we call this process of splitting glucose into two pyruvic sugars? That’s glycolysis (glyco=glucose, and -lysis is to break down). When there’s not enough oxygen, pyruvic acid is converted into lactic acid. When oxygen becomes available, lactic acid is converted back to pyruvic acid. Remember that this all occurs in the cytoplasm. The pyruvates are then, aerobically, broken apart in the mitochondria into Acetyl-CoA. The acetyl sugars are put into the Krebs citric acid cycle and they are totally broken Continue reading >>

More in ketosis