Pyrimidine Catabolism and Salvage Reactions

by Kevin Ahern, PhD

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    00:00 Well, let’s now consider the catabolic and salvage reactions that occur with pyrimidine nucleotides.

    00:08 The pathways of catabolism and salvage for the pyrimidines overlap. That is because there's very easy interconversion of uracil and cytosine-containing nucleotides/nucleosides. There is a similar pathway of breakdown to purines that we start with. Nucleases break the nucleic acids down to nucleoside monophosphates. Nucleotidases convert the nucleoside monophosphates to nucleosides by clipping off that last phosphate. However, the nucleosidases that are used in breaking down pyrimidines are not phosphorylases but rather they’re hydrolases that use water to hydrolyze the base, cleave the base away from the sugars. Now, many of the same enzymes, as I’ve mentioned earlier, work on both cytosine and uracil-containing nucleosides or nucleotides.

    00:56 The breakdown of these converges on the production of uracil. So it’s uracil that we’ll focus on mostly for the catabolism. Thymidine, which is the other type of pyrimidine nucleotide, is handled separately in terms of the breakdown. Now this rather involved pathway here is rather complicated, and again I’m not going to take you to the individual steps. However, I will show you some general tendencies associated with this pathway. We see in the upper left uracil. Uracil is the base that has been produced by the reactions I’ve described so far: the nucleotidases, the hydrolases, and the nucleases that breakdown the RNA. We see it moving to this pathway, that if we go from right to left, they were following breakdown because the molecules for this on the right are triphosphates and those that are on the left are individual bases. As we go up and down, we see exchange. We see the uracil-containing nucleotides on the top and the cytosine-containing nucleotides on the bottom. There is uracil and we therefore think that as we’re going from left to right, we’re starting to build nucleotides instead of breaking them down, those are salvage reactions. Now, all of the salvage reactions and the breakdown reaction and so forth, they’re on the same scheme. It’s simply a question of which direction that they move and as we can see in each of the reactions here, all of the reactions are reversible. So really the direction that a pathway goes depends on the need of a cell. Does the cell need nucleotides to salvage them? It’s going to move in the direction of the right. And does it have excess nucleotides that it needs to use for other purposes? It’s going to break them down in the direction towards the left.

    02:45 Does it need more uracil? It moves up. Does it need more cytosine? It moves down. It’s a very simple scheme looking at it in that way and not as complicated as the reactions that we see here. In this light I follow some of the individual reactions that are involved in breaking down the pyrimidine nucleotides. We see the products of the previous slide where that we got the uracil base. The uracil base came from breakdown of uridine nucleotides and also the breakdown of cytidine nucleotides because they converge on uracil as I noted before. The other nucleotide we have to consider in this breakdown process is that of the thymidine-containing nucleotides because breakdown of them produces the base thymine. Now, I’m not going to say the reactions in detail here but I just note that there are some parallels that happen as removing from the structures on the left to the structures on the right. We get to the end structures which are 3-aminobutyrate for the thymine nucleotides on the top and beta-alanine which is a product of the reactions on the bottom. Each of these molecules can be used in amino acid metabolism and metabolize further. There’s also in a case of each pathway production of ammonium ion and carbon dioxide. Well, we remember from the urea cycle discussion that ammonium ion is toxic and has to be handled in some way and the way in which it’s handled, as we saw in the urea cycle, is that it’s ultimately converted into urea and excreted from the body.

    About the Lecture

    The lecture Pyrimidine Catabolism and Salvage Reactions by Kevin Ahern, PhD is from the course Purine and Pyrimidine Metabolism.

    Included Quiz Questions

    1. All of the answers are true.
    2. None of the answers are true.
    3. It overlaps with salvage synthesis in the reverse direction.
    4. It proceeds through uracil.
    5. It ultimately produces ammonia and carbon dioxide.

    Author of lecture Pyrimidine Catabolism and Salvage Reactions

     Kevin Ahern, PhD

    Kevin Ahern, PhD

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