Synthesis of lipids and N-containing molecules 2

Published on April 19, 2020   44 min

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Greetings. Welcome to this Principles of Biochemistry lecture series. I am Jerry Feigenson, professor in the Department of Molecular Biology and Genetics at Cornell University in the USA. This is the second part of Lecture 21. In the first part, you learned about synthesis of fatty acids and of the more complex phospholipids and fats.
In this second part of this lecture, we study how cholesterol is synthesized, and how it is delivered to cells, and what can go wrong with that delivery. Then we examine how nitrogen becomes a component of biomolecules such as amino acids and heme groups. But first, a brief digression to make more clear a principle of metabolism, what we call activation of molecules.
Now, I've been talking about activation of molecules or making them chemically reactive. Let me summarize what we've seen so far. In fatty acid Beta oxidation, several lectures ago, you saw that the cell first synthesizes the AMP ester and then the CoA thioester of the fatty acid. So those are unstable, they're going to chemically react. And we just briefly talked about this, glucose for glycogen formation, it reacts with the nucleotide UTP to make UDP glucose which is unstable. And we just saw this one, the carbonate that adds to acetyl-CoA, that carbonate has to be made unstable as phosphocarbonate. And for fatty acid formation, we saw malonyl-CoA. Malonyl-CoA has a key role, it's unstable, it's chemically reactive. And we just saw fatty acid for synthesis of fat or phospholipid, the fatty acids have to be made unstable. They form the CoA thioester. Then phosphatidic acid or phospholipid headgroups are made unstable, as the CDP-diacylglycerol or the CDP headgroup. So those are unstable. And this one which we will see in just a moment for cholesterol synthesis, isoprenes are activated as the pyrophosphate derivative. They are now unstable. So what's going on here? Why are these unstable molecules being synthesized? The reason is actually very straight forward. The activated molecules are now unstable and that means that the next reactions become thermodynamically favorable. So we see this activation of molecules happening throughout metabolism. That's why we can say that reactions for biosynthesis are favorable, and reactions for breakdown of molecules are favorable. This involves activation of molecules.

Synthesis of lipids and N-containing molecules 2

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