Paths to Guanine and Adenine Nucleotides

by Kevin Ahern, PhD

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    00:00 IMP Recall is the molecule that was the branch between the synthesis of the adenosine nucleotides and the guanosine nucleotides. We're going to follow those reactions to make both of those sets of nucleotides in some detail here. In going from IMP, in the direction to making the adenosine nucleotides, we see the first molecule formed is Adenylosuccinate.

    00:22 Adenylosuccinate is made from IMP by a transamination reaction that we will see how that happens in just a second. The source of that amine is aspartic acid. This reaction requires energy and the energy comes from the hydrolysis of GTP to make GDP. Now, that energy source might seem...well, first of all, it's a little odd, we see GTP instead of ATP, why is that the case? The reason that is the case is because GTP is a guanosine nucleotide and the cell is trying to make adenosine nucleotides, and if the cell is trying to make adenosine nucleotides, in all likelihood it doesn't have enough. So it couldn't use ATP to make adenosine nucleotides. It uses the other purine, GTP as its energy source. We'll see the same thing happens with the GTP synthesis above.

    01:13 The enzyme catalyzed in this reaction is Adenylosuccinate synthetase and we'll see later that this is an important enzyme in controlling the amount of adenosine nucleotides being made. Now Adenylosuccinate can be made into AMP by simply splitting out a molecule of Fumarate. You may recall earlier in the description of the synthesis of the urea cycle that the putting of the aspartic acid on to a molecule and then removing of Fumarate result in the net transfer to the molecule of an amine. So this is an odd transamination like we see in the urea cycle but the net result is that the molecule has gained an amine. That's how we're making this AMP. To go from AMP to the adenosine diphosphate is a simple reaction catalyzed by an enzyme known as Adenylate kinase that requires energy of ATP, and to make ADP into ATP requires the action of an enzyme known as nucleoside diphosphokinase or NDPK as people referred to it. NDPK turns out to be a very flexible and usable enzyme because it will phosphorylate or catalyze the addition of a phosphate to all of the diphosphates, whether they are purines, pyrimidines, deoxyribonucleotides it doesn't matter. All of the diphosphates will get converted to triphosphates in a reaction catalyzed by NDPK. Well, that completes our synthesis to get to the adenosine nucleotides.

    02:50 Now let's follow the synthesis to make the guanosine nucleotides. In these reactions, we see now going upwards that IMP is converted into XMP, that's xanthine monophosphate, that's what the X stands for, and the first step of that process is actually an oxydation. We see that NAD gains the electrons and become NADH, and XMP is a resulting product. The enzyme catalyzing that reaction is IMP dehydrogenase, and that, too, is an important enzyme for regulation. XMP is converted into GMP, and that requires energy, and guess what, the energy comes from ATP.

    03:31 In this case, ATP is cleaved into AMP, meaning it takes a lot of energy to make that happen. A pyrophosphate is split out in the process. We also see glutamine being converted to glutamate and you remember from the lessons I have had on transamination that those are the 2 things involved in transaminating things, so we see the transamination occurring right here. GMP is converted into GDP by GMP Kinase, and GDP is converted into GTP by what? NDPK.

    About the Lecture

    The lecture Paths to Guanine and Adenine Nucleotides by Kevin Ahern, PhD is from the course Purine and Pyrimidine Metabolism.

    Author of lecture Paths to Guanine and Adenine Nucleotides

     Kevin Ahern, PhD

    Kevin Ahern, PhD

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