hey everyone in this system we talked about ketone body metabolism also known as keto lysis so in a previous lesson we talked about how ketone bodies are produced and where they're produced in the body now in this customer and talked about where in the body they are actually utilized and we're gonna also talk about the pathway that leads to the catabolism of ketone bodies to be used as a source of energy to quickly review the two major ketone bodies are beta-hydroxybutyrate and acetyl acetate with beta hydroxy butyrate being by far the most abundant of the ketone bodies and keep down bodies are produced in the liver during times of fasting and intense exercise and are produced from the beta oxidation of fatty acids and we talked about this in the ketogenesis lesson now again ketone bodies are important as an energy source during fasting and prolonged exercise and their catabolized by peripheral tissues the main ones being the brain in skeletal muscle now in normal fed conditions the beta hydroxy butyrate serum level is in a micro more range but as the time of fasting increases we see that beta hydroxy butyrate serum levels increase at a 16 hour fast we see beta hydroxy butyrate serum levels at about a few hundred micro molars but by a 48-hour fast it's about one to two millimeter other interesting phenomenon that lead to increases in beta hydroxy butyrate levels include intense exercise now intense exercise for about 90 minutes can lead to a beta hydroxy butyrate serum level of a one to two million more so just 90 minutes of intense exercise can lead to similar levels of beta hydroxy butyrate as a 48-hour starvation which is pretty phenomenal now the ketogenic diet is another instance where we see beta hydroxy butyrate levels increase and in fact in a ketogenic diet the levels of beta hydroxy butyrate in the serum are actually consistently above two millimolar so in a ketogenic diet we see that because there are very few carbohydrates consumed ketogenesis occurs at higher level so that's why we actually see a higher levels of beta-hydroxybutyrate in this type of diet now as we mentioned before ketogenesis occurs in the liver and it leads to the production of beta hydroxy butyrate and acetoacetate now we didn't talk about how these ketone bodies are actually transported out of the liver and into the bloodstream and in fact they are actually transported through a specific transporter slc one six a six and they're transported in the blood so once the ketone bodies like beta hydroxy butyrate are in the blood how are they transported through the blood now this has not been very well characterized at this point but it is believed that because the ketone bodies have polar groups such as the hydroxyl groups that they are sufficiently hydrophilic to just simply dissolve in it the aqueous blood so there may not be a need of a transport protein nevertheless when the ketone bodies are transported throughout the blood the two major sites or the two major peripheral tissues that utilize ketone bodies are the brain in the skeletal muscle now with the skeletal muscle it is believed that ketone bodies can simply pass through a plasma membrane through passive diffusion but with the brain because the brain has the blood-brain barrier and the brain itself is impermeable to things such as fatty acids that ketone bodies require specific transporters the mono carboxylate transporters or MC t1 in an MC t2 now these transporters may be located in other peripheral tissues but for the brain it is highly likely that ketone bodies require these transporters to gain entry into the brain now as a quick note these transporters MC t1 and MC t2 are also responsible for transporting pyruvate and lactate across membranes as well now as we mentioned before the two main peripheral tissues that utilize ketone bodies are the brain in skeletal muscle so when the beta-hydroxybutyrate enters one of these peripheral tissues it actually undergoes a reaction with beta-hydroxybutyrate dehydrogenase to form acetyl acetate now you may remember this enzyme because this was actually used in the production of beta hydroxy butyrate as we've seen in the ketogenesis lesson and in the process of metabolizing beta hydroxy butyrate into acetyl acetate and nad plus is reduced to an NADH now the beta hydroxy butyrate dehydrogenase step is a reversible step which means that the direction this enzyme will actually go is under the control of how much any D plus and NADH this cell might have so in a cell that is low in NADH this will favour the reaction from beta hydroxy butyrate to acetyl acetate so that is one of the reasons why we see in the peripheral tissues this reaction can go in the opposite direction as it did in the liver during ketogenesis now we didn't talk about this before in the ketogenesis lecture but this enzyme may be under the regulation of cert 3 which is a deacetylase now again we've mentioned before that acetyl acetate can undergo a spontaneous degradation reaction to form acetone in acetone can be exhaled in the breath now this is just one of the ways that the body can remove and catabolized ketone bodies through this mechanism of acetone generation however this is not very useful for a cell that may require energy so by far the majority of the acetyl acetate in peripheral tissues it's catabolized to acetyl acetyl co a via the enzyme succinylcholine acid coenzyme a transferase or oxy t1 or Scott so this enzyme is where the ketogenesis and keto lysis processes diverge and in fact this enzyme is utilized because it can bypass the hmg-coa lies step of the reaction and because we see a succinylcholine the name in fact succinyl quite and it is used as a coenzyme a donor and as you can see the coenzyme a is actually added to the acetyl acetate and this actually leads to 6:00 in Ocoee be produced or processed into succinate now this enzyme step is the rate limiting step in kita lysis and you may be wondering okay why does this not occur why does keto lysis not occur in the liver and only in peripheral tissues and in it is in fact because the liver does not have this enzyme so the way it is is that the liver is only able to produce ketone bodies but it is not able to utilize the ketone bodies because it does not have the oxy te one enzyme now once we have a seat of acetyl co a the acetyl CoA can be processed with the enzyme thiolase into two acetyl co a which then can be used for the tricarboxylic acid cycle which can then be used to produce nadh and fadh2 for energy production so to summarize keto lysis the oxidation of beta-hydroxybutyrate yields 26 moles of ATP whereas the oxidation of acetyl acetate yields 23 moles of ATP so you might be wondering okay why is there more ATP generated from beta-hydroxybutyrate than acetyl acetate and it is because an NADH was also generated from beta-hydroxybutyrate so during the beta hydroxy butyrate behind Rajan a step where we remember that nad plus was reduced to an NADH now the NADH can be also used in the electron transport chain to produce more ATP around 2.5 ATP so that's why we see a little bit more ATP be generated from beta-hydroxybutyrate in one of the main reasons why the body utilizes ketones as an ER source is to actually spare glucose and this leads to a reduced reliance on glucose so if the brain and the skeletal muscle are not utilizing glucose the glucose levels can be maintained in the bloodstream and in fact red blood cells are almost completely reliant on glucose so this frees up glucose for their utilization anyways guys that was a quick lesson on keto lysis I hope you found this video helpful if you did please like and subscribe for more videos like this one and as always thank you so much for watching and I'll see you next time