[MUSIC] Hello everyone, welcome back to my Coursera class Biochemical Principles of Energy Metabolism. This is the final session of the week five, which is about fat metabolism. So during the previous sessions we talked about adipocyte tissues, biochemistry of fat molecules. And how those fats, dietary fats or stored fats, can be degraded. And right before this session we talked about the beta-oxidation processes to generate a huge amount of ATP molecules from fatty acids. So this session is about fat biosynthesis. So well fat biosynthesis is quite simple. It's not that complicated. So basically this is the biochemical conversion of acetyl-CoA. Again C2-like unit, coenzyme A form can be used for generating fatty acid inside a cytosol. Okay this is about fatty acid biosynthesis. So the interesting point is this one. Carbohydrates like glucose can be used to produce fats in animal cells. Okay fatty acid degradation product of acetyl-CoA can be obviously used for fat upon synthesis. The thing is even glucose breakdown upset the processes. And the accumulated acetyl-CoA from carbohydrates can be used for fat accumulation. However there is no reverse pathway from fat to glucose, because we don't have such enzymatic systems. So over the biochemical formulas like this, to build a main building block for this fatty acid by synthesis, acetyl-CoA, okay? And again this is a biosynthetic process, which is endergonic process, it needs a lot of free energy so we have to consume ATP. And this is reductive process, right? So we need electrons, so NADPH provide electrons. So again huge amount of the reduced electron donors like NADPH supposed to be used. And palmitate, so this is 16 carbon compound. Out of C2, acetyl-CoA, total eight molecules should be used to make one high energy containing palmitic acid. This is kind of the conceptual cartoon showing that carbohydrate digestion inside the mitochondria, the acetyl-CoA level will be high. Or throughout the fatty acid degradation, the beta-oxydation processes, such as acetyl-CoA level will be high. If the target cells undergo biosynthetic metabolic homeostasis, in that case acetyl-CoA can be exported out of mitochondria. And in the cytosol this acetyl-CoA can be used the main substrate to drive fatty acid for energy storage purposes. And those fatty acid out of this acetyl-CoA consumption can be used to store extra energy. In particular inside the adipocyte, fat storing cells. And this process is mediated by fatty acid synthase called FAS, okay? As you can see this three-dimensional beautiful structural cartoon, this enzyme is multifunctional, and multimeric, large molecular weight proteins. Even the each mononer is over 270 kDa. And as you can see there are many catalytic sites and activities associated into this complex. So its main job is in the cytosol of adipocyte or the liver. The 16 carbon long chain palmitate can be produced from acetyl-coenzyme A as a starting point. So step number one of fatty acid biosynthesis is the synthesis of malonyl-CoA, okay? This is the first step of fatty acid synthesis. And C2, two carbon molecule, acetyl-CoA. By consuming ATP we can make the C2 CoA into C3 coenzyme A called malonyl-CoA, okay? So ultimately this is CO2, propylene bicarbonate. So an extra carbon can be attached on top of acetyl-CoA. And we have to use a lot of energy, okay? And this reaction is mediated by acetyl-CoA carboxylase. Acetyl-CoA carboxylase, okay? C, extra carboxylate group is attached. And these, our acetyl-CoA carboxylase indeed is regulated by energy levels, energy conditions. So biosynthesis of fatty acid, again as I said the first type of malonyl-CoA and maybe acetyl-CoA. The substrate can be conjugated and the the first condensation reaction, the CO2 from malonyl-CoA can be released. Released, released away. The second step is reduction, we need more electrons. And dehydration and want more electrons. Each reduction step we consume NADPH electron carriers. So when you see these carbon from reduced oxidized CO, and then more reduced hydroxyl, and then CC double bond, and finally fully reduced CH2 hydrocarbon chains can be produced. In this case those fatty acyl carrier is acyl carrier protein, specialized small polypeptide can be utilized. Okay basically these condensation reduction dehydration reduction processes are totally opposite compared to bad oxidation processes. So a reversal of peroxidal processes but this reaction is taking place inside the cytosome, not mitochondria. So fatty acid degradation processes occur in the mitochondria. But biosynthesis takes place in the cytosome. So synthesis and degradation patiently separate. That's the beauty of this type and the coordinated regulation of fat metabolism inside the cell. So as I said acetyl-CoA carboxylase is the first enzyme triggering and mediating and catalyzing the whole fatty acid biosynthesis. And this enzyme activity is tightly controlled by energy condition as I said. In particular under the energy deficient. Conditions. It's like starvation condition Those condition ATP levels very, very low, instead AMP or ADP level is high. In that case some specialized enzymes like AMP-activated protein kinase, they're activated and then phosphorylate, put extra phosphate on top of acetyl -CoA carboxylase. Acetyl-CoA carboxylase, called ACC. In that case throughout this post-translation phosphorylation, ACC becomes inactive. As you can clearly understand, acetyl-CoA carboxylase is the first critical enzyme for driving energy consuming biosynthetic processes, right? So in that case, under energy deficient condition specialized kinase like AMP-activated protein kinase stop this reaction by phosphorylating and suppressing the ACC activity. Thus shutting down the energy consuming and electron consuming highly expensive fat metabolic, anabolic in this case, fatty acid's biosynthetic processes. This is one of. Good one of the examples showing the tight regulation of bioenergetics in terms of. Energy dependent enzyme regulation. So in this session five, in the very beginning I gave you the sort of overview of adipose tissue. And then the structure of fat molecules and how fat molecules can be digested from diet. And then where the how stored the fat can be used to supply the free fatty acid. And the core of fatty acid degradation is beta-oxidation. And that reaction occurs inside the mitochondria, right? And depending on the energy conditions a fatty acids can be synthesized from acetyl-CoA throughout the ATP consumption and reduction processes, right? And that reaction occurs in the cytosol. And finally I gave a clear example showing the type regulation of bioenergetic processes throughout this post-transfer modification.
