De novo synthesis of purine nucleotides.�provide every information involved in the synthesis and the answer should be about 4 pages

Answer 1

De novo synthesis of purine nucleotides is a complex biochemical pathway that involves the synthesis of purine bases and their subsequent conversion into purine nucleotides. Purine nucleotides are essential components of DNA, RNA, ATP, GTP, and other important molecules in cells. The de novo synthesis pathway is the primary pathway for the production of purine nucleotides in cells, as opposed to salvage pathways that involve the recycling of purine bases from nucleic acid breakdown.

The de novo synthesis of purine nucleotides begins with the synthesis of the purine base inosine monophosphate (IMP), which serves as a precursor for all other purine nucleotides. The overall pathway can be broken down into several key steps, each catalyzed by specific enzymes and requiring specific substrates and cofactors.

Step 1: Formation of 5-phosphoribosyl-1-pyrophosphate (PRPP)
The first step in the de novo synthesis of purine nucleotides is the formation of PRPP, which serves as the activated form of ribose for purine biosynthesis. PRPP is synthesized from ribose 5-phosphate and ATP by the enzyme PRPP synthetase. This reaction is essential for the subsequent steps in the pathway, as PRPP is a key substrate for the synthesis of purine bases.

Step 2: Formation of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR)
In the second step of the pathway, PRPP is converted into AICAR through a series of enzymatic reactions. The enzyme phosphoribosylamine-glycine ligase catalyzes the formation of glycinamide ribonucleotide (GAR) from PRPP and glycine. GAR is then converted into AICAR by the enzyme phosphoribosylamine-glycine ligase. AICAR serves as an intermediate in the synthesis of IMP.

Step 3: Formation of inosine monophosphate (IMP)
A series of enzymatic reactions catalyzed by the enzymes adenylosuccinate synthetase, adenylosuccinate lyase, and IMP dehydrogenase convert AICAR into IMP. These reactions involve the addition of a carboxylic acid group, the removal of fumarate, and the oxidation of the molecule, resulting in the formation of IMP. IMP is the first purine nucleotide synthesized in the pathway and serves as a precursor for the synthesis of other purine nucleotides.

Step 4: Synthesis of adenosine monophosphate (AMP) and guanosine monophosphate (GMP)
IMP serves as a precursor for the synthesis of both AMP and GMP, which are the two other purine nucleotides required for DNA and RNA synthesis. The pathway branches off at IMP, with specific enzymes catalyzing the conversion of IMP into either AMP or GMP. The conversion of IMP into AMP involves a series of reactions catalyzed by adenylosuccinate synthetase, adenylosuccinate lyase, and adenylate kinase. The conversion of IMP into GMP involves reactions catalyzed by IMP dehydrogenase, GMP synthetase, and GMP reductase.

Overall, the de novo synthesis of purine nucleotides is a tightly regulated pathway that requires the coordinated action of multiple enzymes and substrates. Dysregulation of this pathway can lead to abnormalities in purine nucleotide metabolism, which can result in diseases such as gout, Lesch-Nyhan syndrome, and certain types of cancer. Understanding the mechanisms involved in purine nucleotide synthesis is important for developing targeted therapies for these diseases and advancing our knowledge of cellular metabolism.