Nucleotide synthesis

Nucleotide synthesis refers to the biochemical process by which cells produce nucleotides, the building blocks of DNA and RNA. This process is crucial for cell division, DNA replication, and gene expression, making it essential for all forms of life.

Types of Nucleotide Synthesis

Nucleotide synthesis can be divided into two main pathways:

• De novo synthesis - Nucleotides are synthesized from small molecules such as amino acids, carbon dioxide, and ammonia.
• Salvage pathways - Preformed bases and nucleosides are recycled from cellular turnover or from the diet.

De Novo Synthesis

De novo synthesis of nucleotides involves several enzyme-catalyzed reactions that build the nucleotide from simple molecules. This pathway is energy-intensive but crucial for maintaining adequate nucleotide pools in the cell.

Purine Synthesis

De novo purine synthesis begins with the precursor ribose 5-phosphate, which is converted into inosine monophosphate (IMP), a precursor to other purine nucleotides such as adenosine monophosphate (AMP) and guanosine monophosphate (GMP). This pathway involves multiple steps, each catalyzed by specific enzymes.

Pyrimidine Synthesis

De novo pyrimidine synthesis starts with the formation of carbamoyl phosphate and aspartate to form orotic acid, which is later converted into uridine monophosphate (UMP). UMP can then be converted into other pyrimidine nucleotides such as cytidine monophosphate (CMP) and thymidine monophosphate (TMP).

Salvage Pathways

The salvage pathways recycle free bases and nucleosides released during DNA and RNA turnover. These components are converted back into nucleotides by specific enzymes, such as adenine phosphoribosyltransferase for adenine and hypoxanthine-guanine phosphoribosyltransferase for guanine and hypoxanthine.

Regulation of Nucleotide Synthesis

The synthesis of nucleotides is tightly regulated to balance supply with cellular demand. This regulation ensures that the cell maintains a sufficient supply of nucleotides for DNA replication and repair without excessive accumulation, which can be toxic.

Feedback Inhibition

Key enzymes in the nucleotide synthesis pathways are subject to feedback inhibition, where the end products (nucleotides) inhibit the activity of the first enzyme in the pathway, thus controlling the rate of synthesis.

Clinical Significance

Disruptions in nucleotide synthesis can lead to various genetic disorders and are a target for chemotherapy drugs. For example, drugs that inhibit nucleotide synthesis, such as methotrexate and 5-fluorouracil, are used to treat cancer by limiting the ability of cancer cells to proliferate.

See Also

• DNA replication
• Gene expression
• Metabolism