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Catabolism of Guanine Nucleotides and Adenine Nucleotides

by Kevin Ahern, PhD
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    00:00 Well we’ve now completed the de novo synthesis of both the purines and pyrimidines. Well, it’s time for us to turn our attention to the breakdown of those nucleotides and how those pieces can be salvaged to make nucleotides in another way. This involves catabolism, and I want to start with catabolism of the guanine nucleotides. Nucleotides in nucleic acids are there as monophosphates.

    00:23 They started as triphosphates but during their polymerization process, 2 of the phosphates are lost, so the final nucleic acid has monophosphates in there. If we break down those nucleic acids, whether it’s RNA or it’s DNA, we end up with nucleoside monophosphates as you can see here. That reaction is catalyzed by enzymes known as nucleases. In the case of RNA breaking down enzymes, they’re known as RNAses, and the case of enzymes that break down DNA, they’re known as DNAses. This produces nucleoside monophosphates that would be in the case of RNA, AMP, GMP, CMP, and UMP. Those nucleoside monophosphates can have their phosphate removed, and when that happens, you end up with just nucleosides and those reactions are catalyzed by enzymes known as nucleotidases. Finally, the nucleosides can be broken down into bases into sugars that make them. The sugar, of course, in the case of RNA being ribose. Those reactions are catalyzed by enzymes with a variety of names, and we won’t worry about that for the moment. So, in the case of RNA we see here and RNAse that catalyzes the reaction, we see one of the nucleoside monophosphates, in this case here GMP guanosine monophosphate and then the removal of the phosphate results in the nucleoside guanosine that’s catalyzed by a purine nucleotidase, and then finally, at the bottom, we see a production of the base guanine and the ribose 1-phosphate to ribose sugar. The enzyme that breaks the nucleoside down to the bases and sugars is known as a purine nucleoside phosphorylase and that’s like I said, an enzyme or different enzymes have slightly different names for that. The breakdown of the adenine nucleotides is similar to that of the GMP nucleotides but we see that there’s a couple of ways that the adenine nucleotides can be broken down. We see, first of all, the same starting point that RNA or DNA has broken down into nucleoside monophosphates. In the case of RNA, the enzyme is an RNase and we see production of an AMP. AMP can be then converted into a breakdown product in 2 different ways; one is we can go and make nucleosides as we did before using a purine nucleotidase to end up with adenosine and that simply is involving the loss of the phosphate off of the left side of the AMP. But alternatively, the nucleoside monophosphate can be deaminated.

    02:50 In this case, the base is having an amine group removed from it. The enzyme catalyzing that is an AMP deaminase. The product of that deamination is a different nucleotide known as inosinic acid or IMP. Inosinic acid is that IMP that we saw on the branch point earlier during the synthesis and IMP can be converted into inosin by removal of the phosphate via nucleotidase. So, we’re seeing this served as sidestep to get to the same point, and these are going to end up at the same point in just a second. To get from adenosine down to inosin is, again, a simple deamination that’s happening from there and this deamination is catalyzed by the enzyme, adenosine deaminase.

    03:35 The inosin in this case can then have the base split away from the sugar just like we saw with the guanosine nucleotides to produce ribose 1-phosphate and hypoxanthine. Now, hypoxanthine we'll see is an important salvage molecules, we get to there. The enzyme catalyzing this reaction is a purine nucleoside phosphorylase. Phosphorylases are enzymes that use phosphate to break bonds. Now, the same thing happened with the guanine nucleotides. I didn’t say that, but the important thing is the phosphate is coming in as the molecule doing the cleaving. That ‘s what gives us the ribose 1-phosphate.


    About the Lecture

    The lecture Catabolism of Guanine Nucleotides and Adenine Nucleotides 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. Nucleases break down nucleic acids to nucleotides.
    4. Nucleoside monophosphates are the products of the action of nucleases.
    5. Guanosine is broken down to guanine and ribose-1-phosphate
    1. It produces IMP and inosine.
    2. It produces adenosine as an end product.
    3. It uses a nucleotidase that adds phosphate.
    4. All of the answers are true.
    5. None of the answers are true.

    Author of lecture Catabolism of Guanine Nucleotides and Adenine Nucleotides

     Kevin Ahern, PhD

    Kevin Ahern, PhD


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