nucleotide biosynthetic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of nucleotides, any nucleoside that is esterified with (ortho)phosphate or an oligophosphate at any hydroxyl group on the glycose moiety; may be mono-, di- or triphosphate; this definition includes cyclic-nucleotides (nucleoside cyclic phosphates). [GOC:go_curators]

Nucleotide biosynthesis is a fundamental biological process that involves the synthesis of nucleotides, the building blocks of DNA and RNA. These molecules play crucial roles in various cellular functions, including genetic information storage, protein synthesis, and energy transfer.

The process can be broadly divided into two major pathways: de novo synthesis and salvage pathways.

**De Novo Synthesis**

This pathway involves the synthesis of nucleotides from simpler precursors. It begins with the synthesis of purine and pyrimidine bases, which are then attached to a ribose-5-phosphate molecule to form nucleoside monophosphates (NMPs). The key steps in de novo purine biosynthesis include the sequential addition of amino acids and other small molecules to a pre-existing ribose-5-phosphate molecule. Pyrimidine biosynthesis involves the formation of a pyrimidine ring structure from a carbamoyl phosphate and aspartate.

Once the NMPs are formed, they are further phosphorylated to diphosphates (NDPs) and triphosphates (NTPs). This phosphorylation is crucial for the incorporation of nucleotides into DNA and RNA.

**Salvage Pathways**

The salvage pathways utilize pre-existing purine and pyrimidine bases or nucleosides that are obtained from the breakdown of nucleic acids. These molecules are converted into NMPs and then further processed into NDPs and NTPs. Salvage pathways are crucial for maintaining nucleotide pools and reducing the need for de novo synthesis, which is a more energy-intensive process.

**Regulation**

Nucleotide biosynthesis is tightly regulated at multiple levels to ensure a balanced supply of nucleotides for DNA and RNA synthesis. The availability of precursors, the activity of enzymes, and the feedback inhibition mechanisms are all involved in regulating this process.

**Clinical Significance**

Disruptions in nucleotide biosynthesis can lead to various genetic disorders. These disorders often involve defects in enzymes involved in nucleotide metabolism, leading to the accumulation of toxic metabolites or deficiencies in essential nucleotides. Examples include Lesch-Nyhan syndrome, a severe neurological disorder caused by a deficiency in hypoxanthine-guanine phosphoribosyltransferase (HGPRT), an enzyme involved in purine salvage, and orotic aciduria, a disorder caused by a deficiency in uridine monophosphate synthase (UMPS), an enzyme involved in pyrimidine biosynthesis.

Overall, nucleotide biosynthesis is a complex and highly regulated process that is essential for all living organisms. Understanding the intricate details of this pathway is crucial for comprehending fundamental cellular processes and for developing therapies for genetic disorders associated with nucleotide metabolism.'
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Proteins (4)

Compounds (37)