Ketone Bodies: Study with Video Lessons, Practice Problems & Examples

Ketone bodies, including Acetone, Acetoacetate, and 3-Hydroxybutyrate, are produced from Acetyl CoA in the liver during low carbohydrate availability, starvation, or diabetes. The process involves food catabolism stages, where fatty acids are activated using ATP and undergo beta-oxidation. Ketogenesis includes condensation, hydrolysis, and reduction reactions, leading to the formation of ketone bodies. In low carbohydrate states, oxaloacetate depletes, causing ketosis and potentially ketoacidosis, which acidifies blood pH. Understanding these metabolic pathways is crucial for grasping energy utilization and the implications of carbohydrate deficiency.

Ketone Bodies Concept 1

Hey, everyone. So when we say ketone bodies, these are our three Acetyl CoA metabolites produced in the mitochondria of the liver. And we're going to see that they are used as an energy source by the heart, skeletal muscles, and brain when glucose is not available. Now, you'll need to know what these three ketone bodies look like and when we talk about them, we're going to say two of them are ketones. Hence the name ketone bodies. But then the last one has an alcohol group and is represented as a carboxylic acid as well. So here, the first ketone body is our Acetone. Here, we'd have this central carbon being our carbonyl carbon, meaning it's an acetyl bond O. Next, we have Acetoacetate. So, here we have a carboxylic acid group that has lost its H positive, so it's in its conjugate base form. It is also a ketone and it's this carbon here that is the carbonyl carbon. Then finally, the last one we have that is not a ketone, it is a 3-hydroxybutyrate. Here we're going to say, hydroxy means an OH group. We say that the carbonyl carbon here is carbon 1, this is 2, 3, and 4. So we're going to say that carbon number 3 is where the OH will be. So this represents our three different types of ketone bodies. Again, you're going to need to remember what they look like and the names that are attached to them.

Ketone Bodies Concept 2

Now, we take a look at an overview of food catabolism. Remember, we have stage 1. In stage 1, we are going to digest our lipids which breaks them up into their fatty acids and glycerol components. Remember, here we're looking at the fatty acids. The fatty acid has to be activated, so we have to consume ATP. Remember, there is a one-time cost of 2 ATPs to do this. Doing this helps us to activate our fatty acid and change it into this fatty acid acyl CoA. All this occurs within the cytosol. We're going to say here, it then passes into the mitochondrial matrix where we have beta oxidation, and we're going to have the formation of Acetyl Co_A. Now, ketogenesis is just the synthesis of ketone bodies from Acetyl Co_A. We're going to say this occurs during low carbohydrate diets, starvations, or due to diabetes. So instead of continuing on to stages 3 and 4 of food catabolism, we're going to move downward this way towards ketogenesis, thus creating ketone bodies. So just remember, in order for ketone bodies to form, we need to utilize Acetyl Co_A. And this occurs when we have low carbohydrates available, when we are in starvation, or when we have diabetes.

Ketone Bodies Concept 3

Now, beta oxidation of a fatty acid produces excess amounts of Acetyl CoA that cannot be processed by the citric acid cycle. Here, we're going to say that in low levels of carbohydrates, our oxaloacetate stores are depleted. Recall that gluconeogenesis creates and uses this oxaloacetate. If we take an overview of the Citric Acid Cycle or Krebs Cycle, oxaloacetate is produced in the final stage. It can join with Acetyl CoA in the formation of citrate to begin another cycle of the Krebs cycle. If our carbohydrate levels are low, then during glycolysis, a low amount of pyruvate would be formed. This would interfere with the production of oxaloacetate.

In this scenario, we encounter ketosis, a condition where large amounts of ketone bodies are present in the blood and the urine. We're going to say here that two of the ketone bodies, remember, are carboxylic acids in nature, and cause ketoacidosis. From the name acid, it acidifies our blood, causing a decrease in the blood pH. This type of condition is mainly in diabetics, so it is not common unless you are diabetic. Just remember that dealing with this low amount of carbohydrates can be detrimental to the pH balance of our blood, creating this condition of ketoacidosis.

Ketone Bodies Example 1

Here it says, "Which statement best describes the process of ketogenesis?" Now, remember, ketogenesis itself is the synthesis of ketone bodies from acetyl-CoA. This typically happens when we're on a low carbohydrate diet, are in starvation mode, or if we are diabetic. Now, here we're going to say ketone bodies are synthesized in the mitochondria of adipose cells. Here, that's not true. It's not in the mitochondria of adipose cells. It's in the mitochondria of the liver. Excess glucose leads to the formation of ketone bodies from pyruvate. Now, remember, ketone bodies happen when we're dealing with a low carbohydrate diet. So we wouldn't have an excess of glucose, we'd have a deficiency of glucose. Ketone bodies are synthesized from oxaloacetate, which is a metabolite that is converted from excess acetyl-CoA. Alright. So here, there's a lot to be said here in terms of this. Ketone bodies are synthesized from acetyl-CoA itself, not oxaloacetate. And we're going to say here that oxaloacetate can work in conjunction with acetyl-CoA to create citrate. So there's a lot wrong with this sentence. Ketogenesis occurs as a result of a deficiency of glucose. That's true. It can cause high levels of acetoacetate in the blood. Now, acetoacetate represents one of the carboxylic acid ketone bodies. A lot of that would create a condition known as ketoacidosis, which can happen if we have too many ketone bodies within our blood and urine. So here, this statement is the most true out of all the statements given to us. The final answer is option D.

Ketone Bodies Concept 4

Here in this video, we're going to talk about the 1st ketogenesis reaction, which is a condensation reaction. Within it, we have 2 Acetyl CoA molecules that condense forming a 4 Carbon intermediate. Now here, this can be seen as the reverse of the last step of beta oxidation. If we take a look here at this reaction, we have 2 Acetyl CoA molecules, and we're going to say that they're going to join together to create this acetyl acetyl CoA. Now, in order to do this, we're going to have to have the loss of our CoA thiol here or SH group actually. And we're going to say here, the easiest way to think about what occurs is we'd have the loss of the Sulfur in CoA and a Hydrogen from this methyl group. So those are lost. What is left behind is what comes together to make my product. So we have left this methyl group and this carbonyl, which is this portion here. We're going to say that this CH₃ is no longer a CH₃. It's lost a hydrogen, so it's a CH₂ now, which is because it's still connected to this carbonyl, sulfur, and CoA. Carbonyl, sulfur, and CoA. They are joined together by this bond. So remember, this is condensation. We have the loss of CoA SH in order to create this acetyl acetyl CoA as a product.

Ketone Bodies Concept 5

Now our second reaction under ketogenesis is hydrolysis. This is going to be the cleavage of an Acetyl CoA which forms our first ketone body here in relation to Acetoacetate. So here we're creating Acetoacetate. We have our Acetyl CoA. We're going to utilize water because this is a hydrolysis. We're going to utilize water, and that's going to help us lose this sulfur component. What we're going to have is an oxygen being placed here, so we've just made a carboxylate anion end to help us make our Acetoacetate. Alright. So just remember, in this first one, we're doing the cleavage of our Acetyl CoA that we made under the condensation reaction before this one. Right. So, in order to make our first ketone body.

Ketone Bodies Concept 6

Now, in our continued discussion of the ketogenesis reactions, we are at step 3 where we have a reduction in decarboxylation. Here, we have Acetyl Acetate in the center, and we're going to say that it is reduced to form our second ketone body, which is 3-Hydroxybutyrate. If we take a look here, we have Acetoacetate. We're going to use NADH. It is going to become oxidized to create NAD⁺. Because NADH is oxidized, that means Acetoacetate is reduced. It gets reduced into 3-Hydroxybutyrate. Here, this would be carbon 1, 2, 3, and 4. On carbon 3, we have a hydroxy. Again, remember that just means an OH group. So, if we've reduced our ketone to a secondary alcohol to make 3-Hydroxybutyrate. Also, we can say, when in the bloodstream, some Acetoacetate can also be decarboxylated in order to form Acetone. Here, we'd have decarboxylation, and we have the loss of carbon dioxide. Doing this would help us to form our acetone, which is yet another ketone body. Alright. So, just remember, this third step we can look at it in terms of reduction going from Acetoacetate to 3-Hydroxybutyrate, or we can look at it as a decarboxylation where Acetoacetate undergoes decarboxylation to create acetone.

Ketone Bodies Example 2

Here in this example question, it says the ketone body produced during the hydrolysis reaction of ketogenesis is. So, first of all, remember there are three ketone bodies: Acetoacetate, Acetone, and 3-Hydroxybutyrate. Option c, Acetate isn't a ketone body, so it's out. The answer here would be option a. Option a, Acetoacetate is created through a hydrolysis reaction, and it happens when we have acetoacetyl-CoA undergoing a hydrolysis reaction to create Acetoacetate. Here, acetone is created from Acetoacetate by decarboxylation, not hydrolysis. And 3-Hydroxybutyrate is created through Acetoacetate as well, but through a reduction. So again, the only answer here that's created through hydrolysis will be option a, Acetoacetate.

Which reaction produces a ketone body with an alcohol functional group? Draw the ketone body.

• A. condensation
• B. hydrolysis
• C. reduction
• D. decarboxylation

How is oxaloacetate related to ketone bodies formation?

• A. High levels of acetyl CoA accumulate and increase the rate of citric acid cycle.
• B. Oxaloacetate combines with acetyl CoA to form citrate; this leads to formation of ketone bodies.
• C. Citric acid cycle is not dependent on oxaloacetate, and all acetyl CoA is free to be oxidized in the cycle.
• D. Ketone bodies are formed when oxaloacetate levels are low.
• E. Ketogenesis can speed up gluconeogenesis by producing more oxaloacetate.

Here’s what students ask on this topic:

What are the three types of ketone bodies and their chemical structures?

The three types of ketone bodies are Acetone, Acetoacetate, and 3-Hydroxybutyrate. Acetone has a simple structure with a central carbonyl carbon (C=O) bonded to two methyl groups (CH₃). Acetoacetate is a carboxylic acid with a ketone group, represented as CH₃-CO-CH₂-COO^-. 3-Hydroxybutyrate is not a ketone but an alcohol, with the structure CH₃-CH(OH)-CH₂-COO^-. These structures are crucial for understanding their roles in metabolism.

How are ketone bodies produced in the liver?

Ketone bodies are produced in the liver through a process called ketogenesis, which occurs during low carbohydrate availability, starvation, or diabetes. The process begins with the activation of fatty acids, which are then converted to Acetyl CoA via beta-oxidation. Acetyl CoA undergoes a series of reactions: condensation to form Acetoacetyl CoA, hydrolysis to produce Acetoacetate, and reduction or decarboxylation to form 3-Hydroxybutyrate or Acetone, respectively. These ketone bodies are then released into the bloodstream for energy use by other tissues.

What is ketoacidosis and how does it affect the body?

Ketoacidosis is a condition characterized by high levels of ketone bodies in the blood, leading to a decrease in blood pH, making it more acidic. This condition is most commonly seen in diabetics and can be life-threatening if not managed properly. The excess ketone bodies, particularly Acetoacetate and 3-Hydroxybutyrate, are acidic and can disrupt the body's acid-base balance, leading to symptoms such as nausea, vomiting, abdominal pain, and confusion. Severe cases can result in diabetic coma or death.

What role does oxaloacetate play in ketogenesis?

Oxaloacetate plays a crucial role in the citric acid cycle by combining with Acetyl CoA to form citrate. However, during low carbohydrate states, oxaloacetate is depleted because it is diverted to gluconeogenesis to produce glucose. This depletion prevents Acetyl CoA from entering the citric acid cycle, leading to its accumulation. The excess Acetyl CoA is then used in ketogenesis to produce ketone bodies. Thus, the availability of oxaloacetate directly influences the shift towards ketone body production.

What are the stages of food catabolism leading to ketogenesis?

Food catabolism leading to ketogenesis involves several stages. In stage 1, lipids are digested into fatty acids and glycerol. Fatty acids are then activated in the cytosol, consuming ATP to form fatty acid acyl CoA. This acyl CoA is transported into the mitochondrial matrix, where beta-oxidation occurs, producing Acetyl CoA. During low carbohydrate availability, instead of entering the citric acid cycle, Acetyl CoA undergoes ketogenesis, forming ketone bodies. This process includes condensation, hydrolysis, and reduction reactions, ultimately producing Acetone, Acetoacetate, and 3-Hydroxybutyrate.