Ketosis: What Is Ketosis?
Ketosis is a normal metabolic process. When the body does not have enough glucose for energy, it burns stored fats instead; this results in a build-up of acids called ketones within the body. Some people encourage ketosis by following a diet called the ketogenic or low-carb diet. The aim of the diet is to try and burn unwanted fat by forcing the body to rely on fat for energy, rather than carbohydrates. Ketosis is also commonly observed in patients with diabetes, as the process can occur if the body does not have enough insulin or is not using insulin correctly. Problems associated with extreme levels of ketosis are more likely to develop in patients with type 1 diabetes compared with type 2 diabetes patients. Ketosis occurs when the body does not have sufficient access to its primary fuel source, glucose. Ketosis describes a condition where fat stores are broken down to produce energy, which also produces ketones, a type of acid. As ketone levels rise, the acidity of the blood also increases, leading to ketoacidosis, a serious condition that can prove fatal. People with type 1 diabetes are more likely to develop ketoacidosis, for which emergency medical treatment is required to avoid or treat diabetic coma. Some people follow a ketogenic (low-carb) diet to try to lose weight by forcing the body to burn fat stores. What is ketosis? In normal circumstances, the body's cells use glucose as their primary form of energy. Glucose is typically derived from dietary carbohydrates, including: sugar - such as fruits and milk or yogurt starchy foods - such as bread and pasta The body breaks these down into simple sugars. Glucose can either be used to fuel the body or be stored in the liver and muscles as glycogen. If there is not enough glucose available to meet energy demands, th Continue reading >>
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 >>
Getting To Know Ketones
People with diabetes, particularly those with Type 1 diabetes, have been at least vaguely aware of the word ketones for a long time. With the recent resurgence of popular interest in low-carbohydrate diets, however, just about everyone seems to be talking about ketones these days. But does anyone really know what ketones are? Are they a danger to your health (as in diabetic ketoacidosis), or a sign that you have lowered your carbohydrate intake enough to cause weight loss (as some people who follow low-carbohydrate diets believe)? What are ketones? Ketones are end-products of fat metabolism in the body. That is, they are formed when fat is burned for energy by the muscles. Chemically, they are acids known as ketone bodies, and there are three types: beta-hydroxybutyric acid, aceto-acetic acid, and acetone. But you don’t have to be a chemist to understand what role they play in the body. To get to know ketones, it’s helpful to understand how your body burns fuel. A simple analogy is that of an automobile. For a car engine to run, the engine must burn fuel (gasoline), and when the fuel is burned, exhaust (carbon monoxide) is created. The carbon monoxide is the end-product of gasoline combustion. Your body also has an engine that must burn fuel to operate. The engine is muscle, and the fuel is fat, carbohydrate (glucose), and, in certain conditions, protein. When fat is burned, the “exhaust” is ketones, and when glucose is burned, the “exhaust” is lactic acid. Fat is more desirable as a fuel than glucose because there are more calories in a gram of fat (9 calories per gram) than there are in a gram of glucose (4 calories per gram), so you get more energy per gram of fat burned. In a sense, you could call fat a high-test fuel. But there is one catch to burning f Continue reading >>
Regulation Of Ketone Body Production: Answer
What regulates ketone body synthesis? The primary regulator of ketone body synthesis is fatty acid availability. When hormonal conditions (e.g., high glucagon, low insulin) cause fatty acid concentration in the plasma to be high, malonyl CoA concentration in the liver cytoplasm is low (because acetyl CoA carboxylase is in the less active phosphorylated state). Fatty acyl CoA can enter the mitochondria at a high rate (because there is no inhibition of CAT I), and beta-oxidation proceeds at a high rate. The ensuing high mitochondrial concentration of acetyl CoA results in active ketone body synthesis. Continue reading >>
Long Term Exposure To Fatty Acids And Ketones Inhibits B-cell Functions In Human Pancreatic Islets Of Langerhans.
Abstract We previously demonstrated in the rat that long term exposure to fatty acids inhibits B-cell function in vivo and in vitro. To further assess the clinical significance of these findings, we tested in human islets the effects of fatty acids on glucose-induced insulin release and biosynthesis and on pyruvate dehydrogenase (PDH) activity. Human islets were obtained from the beta-Cell Transplant Unit (Brussels, Belgium). Exposure to 0.125 mmol/L palmitate or oleate for 48 h during tissue culture (RPMI-1640 and 5.5 mmol/L glucose) inhibited the postculture insulin response to 27 mmol/L glucose by 40% and 42% (P < 0.01 for difference). Inhibition was partly prevented by coculture with 1 mumol/L etomoxir, a carnitine-palmitoyl-transferase-I inhibitor (P < 0.05 for effect of etomoxir). Inhibitory effects on glucose-induced insulin secretion by previous palmitate were additive to the inhibitory effects exerted by previous high glucose (11 and 27 mmol/L). Palmitate-induced inhibition of insulin secretion was evident after exposure to 25 mumol/L added fatty acid. The insulin content of islets exposed to fatty acids was significantly reduced, and glucose-induced proinsulin biosynthesis was inhibited by 59% after palmitate addition and by 51% after oleate exposure (P < 0.01). These effects were partly prevented by etomoxir (P < 0.05). The activity of PDH in mitochondrial extracts of islets preexposed for 48 h to palmitate was decreased by 35% (P < 0.05) vs. that in control islets, whereas the activity of PDH kinase (which inactivates PDH) was significantly increased in the same preparations (P < 0.05). The effects of ketones were tested by 48-h exposure to beta-hydroxybutyrate (beta-D-OHB). Ten millimoles of D-beta-OHB per L inhibited the subsequently tested insulin respons Continue reading >>
Metabolic Effects Of The Very-low-carbohydrate Diets: Misunderstood "villains" Of Human Metabolism
Go to: The Ketone Bodies are an Important Fuel The hormonal changes associated with a low carbohydrate diet include a reduction in the circulating levels of insulin along with increased levels of glucagon. This activates phosphoenolpyruvate carboxykinase, fructose 1,6-biphosphatase, and glucose 6-phosphatase and also inhibits pyruvate kinase, 6-phosphofructo-1-kinase, and glucokinase. These changes indeed favor gluconeogenesis. However, the body limits glucose utilization to reduce the need for gluconeogenesis. In the liver in the well-fed state, acetyl CoA formed during the β-oxidation of fatty acids is oxidized to CO2 and H2O in the citric acid cycle. However, when the rate of mobilization of fatty acids from adipose tissue is accelerated, as, for example, during very low carbohydrate intake, the liver converts acetyl CoA into ketone bodies: Acetoacetate and 3-hydroxybutyrate. The liver cannot utilize ketone bodies because it lacks the mitochondrial enzyme succinyl CoA:3-ketoacid CoA transferase required for activation of acetoacetate to acetoacetyl CoA . Therefore, ketone bodies flow from the liver to extra-hepatic tissues (e.g., brain) for use as a fuel; this spares glucose metabolism via a mechanism similar to the sparing of glucose by oxidation of fatty acids as an alternative fuel. Indeed, the use of ketone bodies replaces most of the glucose required by the brain. Not all amino acid carbon will yield glucose; on average, 1.6 g of amino acids is required to synthesize 1 g of glucose . Thus, to keep the brain supplied with glucose at rate of 110 to 120 g/day, the breakdown of 160 to 200 g of protein (close to 1 kg of muscle tissue) would be required. This is clearly undesirable, and the body limits glucose utilization to reduce the need for gluconeogenesis Continue reading >>
The Alkaline Diet Vs Acidic Ketones
Whether you think eating alkaline foods is useful or woo woo junk it appears that metabolic acidosis is a thing. Metabolic acidosis seems to be interrelated with insulin resistance, Type 2 Diabetes, and retention of muscle mass. To prevent metabolic acidosis, it appears prudent to ensure that your body has adequate minerals to enable your kidneys to balance pH over the long term. This can be achieved by eating plenty of veggies and/or supplementing with alkaline minerals (e.g. magnesium, sodium, potassium, zinc etc). If you eat plenty of veggies you’re probably getting enough alkalising minerals, however, you can easily test your urine to see if your dietary acid load is high. If you are targeting a high fat therapeutic ketogenic diet, following a zero-carb dietary approach and/or taking exogenous ketones it seems then it may be even more important to be mindful of your acid load and consider mineral supplementation. Recently I had a fascinating, surprising and exciting experience during a fast. The chart below shows my ketones, glucose and ‘total energy’ (i.e. glucose plus ketones) over the seven days. My ketones increased to above 8.0 mmol/L. They even couldn’t be read on my ketone metre! It was the full keto brochure experience. It was like my body fat was effortlessly feeding my brain with delicious, succulent ketones! I felt great. This chart shows my glucose : ketone index (GKI) dropping to below 0.5 after a few days. The orange dots in this chart shows the relationship between glucose and ketones about 18 months ago when I first started trying this keto thing (after I read ‘Jimmy’s Moore’s Keto Clarity’). The blue dots show the relationship between my glucose and ketones during the recent fast. As you can see from the much flatter line, my blood g Continue reading >>
Reactions Of Aldehydes And Ketones
Aldehydes and ketones undergo a variety of reactions that lead to many different products. The most common reactions are nucleophilic addition reactions, which lead to the formation of alcohols, alkenes, diols, cyanohydrins (RCH(OH)C&tbond;N), and imines R 2C&dbond;NR), to mention a few representative examples. The main reactions of the carbonyl group are nucleophilic additions to the carbon‐oxygen double bond. As shown below, this addition consists of adding a nucleophile and a hydrogen across the carbon‐oxygen double bond. Due to differences in electronegativities, the carbonyl group is polarized. The carbon atom has a partial positive charge, and the oxygen atom has a partially negative charge. Aldehydes are usually more reactive toward nucleophilic substitutions than ketones because of both steric and electronic effects. In aldehydes, the relatively small hydrogen atom is attached to one side of the carbonyl group, while a larger R group is affixed to the other side. In ketones, however, R groups are attached to both sides of the carbonyl group. Thus, steric hindrance is less in aldehydes than in ketones. Electronically, aldehydes have only one R group to supply electrons toward the partially positive carbonyl carbon, while ketones have two electron‐supplying groups attached to the carbonyl carbon. The greater amount of electrons being supplied to the carbonyl carbon, the less the partial positive charge on this atom and the weaker it will become as a nucleus. The addition of water to an aldehyde results in the formation of a hydrate. The formation of a hydrate proceeds via a nucleophilic addition mechanism. 1. Water, acting as a nucleophile, is attracted to the partially positive carbon of the carbonyl group, generating an oxonium ion. Acetal formation reacti Continue reading >>
Urine Tests For Diabetes: Glucose Levels And Ketones
The human body primarily runs on glucose. When your body is low on glucose, or if you have diabetes and don’t have enough insulin to help your cells absorb the glucose, your body starts breaking down fats for energy. Ketones (chemically known as ketone bodies) are byproducts of the breakdown of fatty acids. The breakdown of fat for fuel and the creation of ketones is a normal process for everyone. In a person without diabetes, insulin, glucagon, and other hormones prevent ketone levels in the blood from getting too high. However, people with diabetes are at risk for ketone buildup in their blood. If left untreated, people with type 1 diabetes are at risk for developing a condition called diabetic ketoacidosis (DKA). While rare, it’s possible for people with type 2 diabetes to experience DKA in certain circumstances as well. If you have diabetes, you need to be especially aware of the symptoms that having too many ketones in your body can cause. These include: If you don’t get treatment, the symptoms can progress to: a fruity breath odor stomach pain trouble breathing You should always seek immediate medical attention if your ketone levels are high. Testing your blood or urine to measure your ketone levels can all be done at home. At-home testing kits are available for both types of tests, although urine testing continues to be more common. Urine tests are available without a prescription at most drugstores, or you can buy them online. You should test your urine or blood for ketones when any of the following occurs: Your blood sugar is higher than 240 mg/dL. You feel sick or nauseated, regardless of your blood sugar reading. To perform a urine test, you urinate into a clean container and dip the test strip into the urine. For a child who isn’t potty-trained, a pa Continue reading >>
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Is A Ketone An Acid Or A Base?
Ketones are in fact weak acids. This comes from an ability to shift the places of the double bond and one of the hydrogen atoms, resulting in an alcohol compound with a double bond between two of the carbon atoms. This is called an enol, and is less stable than the ketone - the two are in rapid equilibrium. This enol may lose a hydrogen ion to become an enolate. This happens only when a ketone is reacted with a strong base. Continue reading >>
Ketone bodies Acetone Acetoacetic acid (R)-beta-Hydroxybutyric acid Ketone bodies are three water-soluble molecules (acetoacetate, beta-hydroxybutyrate, and their spontaneous breakdown product, acetone) that are produced by the liver from fatty acids during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, prolonged intense exercise,, alcoholism or in untreated (or inadequately treated) type 1 diabetes mellitus. These ketone bodies are readily picked up by the extra-hepatic tissues, and converted into acetyl-CoA which then enters the citric acid cycle and is oxidized in the mitochondria for energy. In the brain, ketone bodies are also used to make acetyl-CoA into long-chain fatty acids. Ketone bodies are produced by the liver under the circumstances listed above (i.e. fasting, starving, low carbohydrate diets, prolonged exercise and untreated type 1 diabetes mellitus) as a result of intense gluconeogenesis, which is the production of glucose from non-carbohydrate sources (not including fatty acids). They are therefore always released into the blood by the liver together with newly produced glucose, after the liver glycogen stores have been depleted (these glycogen stores are depleted after only 24 hours of fasting). When two acetyl-CoA molecules lose their -CoAs, (or Co-enzyme A groups) they can form a (covalent) dimer called acetoacetate. Beta-hydroxybutyrate is a reduced form of acetoacetate, in which the ketone group is converted into an alcohol (or hydroxyl) group (see illustration on the right). Both are 4-carbon molecules, that can readily be converted back into acetyl-CoA by most tissues of the body, with the notable exception of the liver. Acetone is the decarboxylated form of acetoacetate which cannot be converted Continue reading >>
Aldehydes, Ketones, Carboxylic Acids, And Esters
Learning Objectives By the end of this section, you will be able to: Describe the structure and properties of aldehydes, ketones, carboxylic acids and esters Another class of organic molecules contains a carbon atom connected to an oxygen atom by a double bond, commonly called a carbonyl group. The trigonal planar carbon in the carbonyl group can attach to two other substituents leading to several subfamilies (aldehydes, ketones, carboxylic acids and esters) described in this section. Aldehydes and Ketones Both aldehydes and ketones contain a carbonyl group, a functional group with a carbon-oxygen double bond. The names for aldehyde and ketone compounds are derived using similar nomenclature rules as for alkanes and alcohols, and include the class-identifying suffixes –al and –one, respectively: In an aldehyde, the carbonyl group is bonded to at least one hydrogen atom. In a ketone, the carbonyl group is bonded to two carbon atoms: In both aldehydes and ketones, the geometry around the carbon atom in the carbonyl group is trigonal planar; the carbon atom exhibits sp2 hybridization. Two of the sp2 orbitals on the carbon atom in the carbonyl group are used to form σ bonds to the other carbon or hydrogen atoms in a molecule. The remaining sp2 hybrid orbital forms a σ bond to the oxygen atom. The unhybridized p orbital on the carbon atom in the carbonyl group overlaps a p orbital on the oxygen atom to form the π bond in the double bond. Like the C=O bond in carbon dioxide, the C=O bond of a carbonyl group is polar (recall that oxygen is significantly more electronegative than carbon, and the shared electrons are pulled toward the oxygen atom and away from the carbon atom). Many of the reactions of aldehydes and ketones start with the reaction between a Lewis base and Continue reading >>
Excess ketones are dangerous for someone with diabetes... Low insulin, combined with relatively normal glucagon and epinephrine levels, causes fat to be released from fat cells, which then turns into ketones. Excess formation of ketones is dangerous and is a medical emergency In a person without diabetes, ketone production is the body’s normal adaptation to starvation. Blood sugar levels never get too high, because the production is regulated by just the right balance of insulin, glucagon and other hormones. However, in an individual with diabetes, dangerous and life-threatening levels of ketones can develop. What are ketones and why do I need to know about them? Ketones and ketoacids are alternative fuels for the body that are made when glucose is in short supply. They are made in the liver from the breakdown of fats. Ketones are formed when there is not enough sugar or glucose to supply the body’s fuel needs. This occurs overnight, and during dieting or fasting. During these periods, insulin levels are low, but glucagon and epinephrine levels are relatively normal. This combination of low insulin, and relatively normal glucagon and epinephrine levels causes fat to be released from the fat cells. The fats travel through the blood circulation to reach the liver where they are processed into ketone units. The ketone units then circulate back into the blood stream and are picked up by the muscle and other tissues to fuel your body’s metabolism. In a person without diabetes, ketone production is the body’s normal adaptation to starvation. Blood sugar levels never get too high, because the production is regulated by just the right balance of insulin, glucagon and other hormones. However, in an individual with diabetes, dangerous and life-threatening levels of ketone Continue reading >>
Turnover And Splanchnic Metabolism Of Free Fatty Acids And Ketones In Insulin-dependent Diabetics At Rest And In Response To Exercise.
Nine insulin-dependent diabetics and six healthy controls were studied at rest, during, and after 60 min of bicycle exercise at a work load corresponding to 45% of their maximal oxygen intake. The catheter technique was employed to determine splanchnic and leg exchange of metabolites. FFA turnover and regional exchange was evaluated using [14C]oleate infusion. Basal glucose (13.8 +/- 1.1 mmol/l), ketone body (1.12 +/- 0.12 mmol/l), and FFA (967 +/- 110 mumol/l) concentrations were elevated in the diabetics in comparison with controls. In the resting state, splanchnic ketone acid production in the diabetics was 6-10-fold greater than in controls. Uptake of oleic acid by the splanchnic bed was increased 2-3-fold, and the proportion of splanchnic FFA uptake converted to ketones (61%) was threefold greater than in controls. In contrast, splanchnic fractional extraction of oleic acid was identical in diabetics and controls. A direct relationship was observed between splanchnic uptake and splanchnic inflow (plasma concentration X hepatic plasma flow) of oleic acid that could be described by the same regression line in the diabetic and control groups. During exercise, splanchnic ketone production rose in both groups. In the control group the increase in ketogenesis was associated with a rise in splanchnic inflow and in uptake of oleic acid, a rise in splanchnic fractional extraction of oleate, and an increase in the proportion of splanchnic FFA uptake converted to ketone acids from 20-40%. In the diabetic group, the increase in ketogenesis occurred in the absence of a rise in splanchnic inflow or uptake of oleic acid, but was associated with an increase in splanchnic fractional extraction of oleic acid and a marked increase in hepatic conversion of FFA to ketones, so that the Continue reading >>
- Renal Handling of Ketones in Response to Sodium–Glucose Cotransporter 2 Inhibition in Patients With Type 2 Diabetes
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- Exercise and Glucose Metabolism in Persons with Diabetes Mellitus: Perspectives on the Role for Continuous Glucose Monitoring
Why Are Aldehydes And Ketones Neutral And Not Acidic/basic?
This question is quite general, and as other answers have pointed out, depends on what you mean by acidic/basic. The other answers have already covered the Lewis bit, so I will focus a bit more on the Bronsted-Lowry and Arrhenius definitions. In water, almost all aldehydes and ketones do not dissociate to give the H+ or OH- ion, which is the Arrhenius definition. However, the alpha position of acetylacetone is considered acidic by the Bronsted-Lowry definition, and can be deprotonated by strong bases to give the conjugated enone after tautomerism. This is due to the stability of the conjugate base. Continue reading >>