Hello everyone. Welcome back to my Coursera class, Biochemical Principles of Energy Metabolism. We are at session four in week five. Fat metabolism. We've talked about many issues about fat metabolism so far. We had post tissue and biochemical structures of lipids and how fats can be digested from the diet and food, or how fat molecules can be supplied from your stored fat in a deposit. And it is time to talk about oxidation processes of fat molecules. So the sources of fat obviously from the lipids, right? And they are degraded or stored fats can be degraded and transported to other tissues or dietary fats can be digested, chemically digested and then through the circulatory system they can be used for energy production. And at peripheral tissues and those fatty acid are metabolically activated first and then getting into mitochondria for food oxidation. Again, so like a carbohydrate metabolism glucose degradation, fat oxidative processes include mitochondria for major site for energy production. And that was fatty acid getting into the transformed into acetyl-CoA and this is the basic starting point for fat degradation. And citric acid cycle instead of mitochondria is the key biochemical pathway for breakdown of fat. So again, for the fatty acid this is like a overall review cartoon. Fatty acid in the blood. These hydrophobic molecules, they cannot just freely localized or freely available inside the blood. So rather the albumin proteins, the serum albumin is kind of carrier for fatty acid. So target cells, the fatty acid can get into the cytoplasm of target cells through the transporters. There should be fatty acid transporters and definitely fatty acid and activated and transformed into acetyl-CoA. And that acetyl-CoA is used for energy production and the mitochondria is the key organelle for this process like carbohydrate digestion, carbohydrate oxidation pathway. Okay. You are looking at palmitic acid, one of highly abundant fatty acids, saturated fatty acid. How many carbons? 16 carbons. Okay, total 16 carbons. So this palmitic acid, 16 carbon palmitic acid, when they are oxidized into water and carbon dioxide, total 106 ATP can be generated, which is huge, right? Through a specialized pathway called beta oxidation. And we can subdivide into the steps in the very beginning. We consume two ATP molecules, so -2 ATP is kind of investment and activation step. And then later on, 8 acetyl-CoA and reduced electron carrier FADH2 and NADH can be generated. And out of these oxidation, so total plus minus we can produce over 100 ATP molecules. Step number one is fatty acid activation. So, incoming fatty acid for degradation are supposed to be activated. And this activation process include ATP consumption. First we have to invest our free energy ATP. So, reaction is like this, the fatty acid and ATP they reacted with each other and the pyrophosphate out of ATP can be released and then fatty acid chain can be AMP modified, adenylated. And these molecules and incoming Coenzyme A. Again, this Coenzyme A is the key player. It's like glucose degradation even in fat metabolism. So, finally adenylate, fatty acyl-CoA becomes fatty acyl-coenzyme A and then AMP is released. Because these pyrophosphates, again energy containing molecules it can be further degraded into two phosphate molecules and then generate more free energy. And the hydrolysis of pyrophosphate can drive these highly exergonic fatty acid activation biochemical process. And that reaction of course inside cytosol of target cell, peripheral cells. But the main oxidative process occurs inside the mitochondria that beta oxidation takes place inside the mitochondria. So, fatty acyl-CoA should be transported into the mitochondria, mitochondrial matrix. This transport process is a little bit complicated. So acetyl-CoA becomes replaced by carnitine. So another organic compound and carnitine, fatty acid carnitine inside the mitochondrial matrix, again getting back to the acetyl-CoA. So you might be very curious about why this type of complicated transport processes developed for fat oxidation. Well, simply speaking fatty acyl-CoA cannot directly get into mitochondrial matrix. On top of that, this type of transport processes is one of major regulatory points for fat metabolism homeostasis. So what is it then that beta oxidation. Again, this beta oxidation process takes place inside the mitochondria. So you are looking at this very, very simplified cartoon. Okay, fatty acyl-Coenzyme A can be biochemically cut into two carbons. In each cycle, acetyl-CoA can be generated. And then during this oxidative processes, in addition to one acetyl-CoA and shortened fatty acyl-CoA product, FADH2 and NADH can be generated. And those reduced electron carriers inside the mitochondria, they can be used to drive ATP throughout oxidative phosphorylation, OXPHOS pathway we studied in the glucose degradation. So beta oxidation pathway is like this. So this pathway is composed of four steps, okay? In particular, I want to give you why this is called beta oxidation. So in the nomenclature of chemistry, the first carbon from the carboxylic group is alpha carbon. The second carbon from the carboxylic group is called beta carbon, okay? So as you can imagine the beta oxidation pathway means this beta carbon is continuously oxidized throughout this cycle. First the hydrogenation then means oxidation and one reduced FADH2 can be produced and then dehydration, just look at those reduced state of this beta carbon, right? So you see double bond now hydroxylated, oxidised, partly oxidised and further oxidised. And then NADH can be produced. And now this from hydroxyl, the beta carbon now ketone, right? And then cleave's your reaction and the new Coenzyme A getting into this system and the two carbon reduced fatty acyl chain can be produced and then the terminal C2 part can be released acetyl-CoA. So as you can imagine, inside the mitochondria this reduced FADH2 and this NADH can be used to drive the electron transport system and oxidative phosphorylation and ultimately ATP synthesis. And this acetyl-CoA getting into citric acid cycle. So more ATP production can be done. So, this is the summary cartoon. Triglyceride fatty acid supplied and these fatty acid getting into the mitochondria. And fatty acyl-CoA throughout beta oxidation two carbons per cycle. Acetyl-CoA C2, acetyl-CoA can be continuously produced and NADH and FADH2, those reduced electron carriers can be produced. And those are utilized for electron transport system and citric acid cycle. And so every two carbons acetyl-CoA can be successively generated until the entire saturated fatty acid are fully oxidized into CO2 and water. This is how the beta oxidation pathway can be operated inside your cells.
