De novo synthesis of purine nucleotides. provide every information involved in the synthesis and the information must be more than 4 pages.

Answer 1

De novo synthesis of purine nucleotides is a complex biochemical process that involves several enzymatic reactions and regulatory mechanisms. Purine nucleotides are essential components of DNA and RNA, as well as molecules that play important roles in cellular energy metabolism. The de novo synthesis of purine nucleotides occurs in the cytoplasm of all mammalian cells and involves a series of ten enzymatic reactions that convert simple precursors into the final purine nucleotides, adenosine monophosphate (AMP) and guanosine monophosphate (GMP).

The first step in the de novo synthesis of purine nucleotides is the formation of phosphoribosyl pyrophosphate (PRPP) from ribose 5-phosphate. This reaction is catalyzed by the enzyme PRPP synthetase, which requires ATP as a co-substrate. PRPP is a key intermediate in purine nucleotide biosynthesis, as it serves as a substrate for the synthesis of both AMP and GMP.

The next step in the de novo synthesis of purine nucleotides is the formation of 5-phosphoribosylamine, which is catalyzed by the enzyme phosphoribosylamine-glycine ligase. This reaction involves the condensation of PRPP with glycine to form 5-phosphoribosyl-glycine, which is then decarboxylated to form 5-phosphoribosylamine.

5-phosphoribosylamine is then converted into inosine monophosphate (IMP) via several enzymatic steps. The first step in this pathway is the conversion of 5-phosphoribosylamine into 5-phosphoribosyl-1-pyrophosphate (PRPP) by the enzyme phosphoribosylamine synthase. This reaction involves the elimination of a water molecule from 5-phosphoribosylamine to form an imine intermediate, which is then attacked by a second molecule of PRPP to form 5-phosphoribosyl-1-pyrophosphate.

The next step in the synthesis of IMP is the conversion of PRPP into 5-phosphoribosylamine by the enzyme AMP synthetase. This enzyme catalyzes the transfer of an adenyl group from ATP to the primary amino group of 5-phosphoribosylamine, forming an amide bond. This reaction is essential for the synthesis of AMP, as it provides the nitrogenous base adenine.

The final step in the synthesis of IMP is the conversion of 5-phosphoribosylamine into IMP by the enzyme IMP synthetase. This enzyme catalyzes the condensation of 5-phosphoribosylamine with the nitrogenous base hypoxanthine, which is derived from the degradation of purine nucleotides. This reaction results in the formation of 5-phosphoribosylamine-5'-phosphate, which is then converted into IMP by the action of the enzyme phosphoribosylamine-glycine ligase.

IMP is a pivotal intermediate in purine nucleotide biosynthesis, as it serves as a precursor for both AMP and GMP. The synthesis of AMP from IMP involves the addition of an aspartate group, which is derived from the amino acid aspartate. This reaction is catalyzed by the enzyme adenylosuccinate synthetase, which requires GTP as a co-substrate. The formation of adenylosuccinate is followed by the conversion of adenylosuccinate into AMP by the enzyme adenylosuccinate lyase.

In contrast, the synthesis of GMP from IMP involves the addition of a formyl group, which is derived from the amino acid glutamine. This reaction is catalyzed by the enzyme IMP dehydrogenase, which requires NAD+ as a co-substrate. The formation of xanthosine monophosphate (XMP) is followed by the conversion of XMP into GMP by the enzyme nucleotide phosphorylase.

The de novo synthesis of purine nucleotides is tightly regulated by feedback inhibition and allosteric regulation. The key enzymes in this pathway, such as PRPP synthetase, are regulated by the levels of purine nucleotides in the cell. High concentrations of purine nucleotides, such as AMP and GMP, inhibit the activity of PRPP synthetase, thereby reducing the flux through the de novo pathway. In addition, the activity of enzymes such as IMP dehydrogenase is allosterically regulated by the levels of ATP and GTP, which provide feedback signals on the energy status of the cell.

In conclusion, the de novo synthesis of purine nucleotides is a complex biochemical process that involves several enzymatic reactions and regulatory mechanisms. This pathway is essential for the production of purine nucleotides, which are critical components of DNA and RNA, as well as molecules that play important roles in cellular energy metabolism. The tight regulation of this pathway ensures the efficient production of purine nucleotides in response to the metabolic needs of the cell.