Ketone Body Metabolism

00:01 So as I noted earlier, animals have a bit of a dilemma.

00:04 They have a lot of energy stored in the form of fat but they can’t use that fat to directly make glucose.

00:11 And that’s because the breakdown of fat yields fatty acids and the breakdown of fatty acids yields only acetyl-CoA in addition to some glycerol.

00:20 Glycerol can be made into glucose but glycerol has a fairly minor component of fat.

00:26 Most of the energy of fat is in the fatty acids and cannot be made, the acetyl-CoA cannot be made in to glucose.

00:33 Well, glucose is the most important energy source in the cell and it’s used and maintained in a fairly constant level in the body.

00:41 When glucose concentrations fall low, the body needs, in animals, needs to have some sort of a back up source of energy for quick energy release.

00:51 There is a way that animals can use the energy of fatty acids to make quick energy.

00:58 Not to make glucose, but rather to make molecules or ketone bodies.

01:02 And that’s what I’m gonna talk about here.

01:04 Ketone bodies are made starting with acetyl-CoA molecules.

01:09 So we can see the process here with the joining of two acetyl-CoAs.

01:13 The joining of these is catalyzed by the enzyme thiolase, Which is also an enzyme that’s involved in fatty acid oxidation.

01:20 In this process, one molecule of coenzyme A is released in a four carbon molecule called acetoacetyl-CoA is produced as you can see here.

01:31 In the next step of the process, a third molecule of acetyl-CoA is added with release of one of the molecules of CoA, by the enzyme catalyzed by the enzyme HMG-CoA synthase to produce a molecule called Beta-hydroxy-Beta-menthylglutaryl CoA, long mouthful of the name, more commonly called HMG-CoA.

01:55 As we’ll see that molecule has some other importance in just the moment.

01:59 HMG-CoA is cut by the enzyme HMG-CoA lyase splitting out acetyl-CoA to form the first ketone body known as acetoacetate.

02:11 It’s a four carbon molecule as you can see here.

02:14 Now acetoacetate is relatively unstable and so the body will often convert to acetoacetate into a molecule known as Beta-hydroxybutyrate catalyzed by the enzyme Beta-hydroxybutyrate dehydrogenase as you can see here.

02:29 The Beta-hydroxybutyrate is more stable and travels in the blood more readily.

02:34 Acetoacetate on the other hand can readily non-enzymatically be decarboxylated to form the molecule acetone.

02:44 Now HMG-CoA, as I noted, is a very important molecule and this molecule reaction is shown here to make this molecule is important, because not only can HMG-CoA be used to make ketone bodies, it can also be used to make molecule known as cholesterol.

03:02 And so HMG-CoA is therefore a branch point in the synthesis of ketone bodies and ultimately in the synthesis of cholesterol.

03:11 In this side of lectures, I’ve talked about metabolism of pyruvate, we have metabolism of citric acid cycle, the glyoxylate cycle and ultimately talking about the ketone bodies.

03:22 And in each of these processes, the important molecule, acetyl-CoA, plays a central role and we can see the importance of this molecule in the overall metabolism in the cell.