key term - Orotate phosphoribosyltransferase

Definition

Orotate phosphoribosyltransferase is an enzyme that catalyzes the transfer of a phosphoribosyl group from 5-phosphoribosyl-1-pyrophosphate (PRPP) to orotate, forming orotidine monophosphate (OMP). This reaction is a key step in the de novo synthesis of pyrimidine nucleotides, linking the metabolic pathways of carbohydrate metabolism and nucleotide biosynthesis.

5 Must Know Facts For Your Next Test

1. Orotate phosphoribosyltransferase is specifically involved in the first step of the pyrimidine de novo biosynthetic pathway after orotate is formed.
2. The enzyme plays a role in regulating the availability of pyrimidine nucleotides necessary for DNA and RNA synthesis.
3. Deficiency in orotate phosphoribosyltransferase can lead to orotic aciduria, a genetic disorder characterized by an accumulation of orotic acid in urine.
4. Inhibitors of orotate phosphoribosyltransferase can be utilized as potential therapeutic agents in cancer treatments due to their impact on nucleotide synthesis.
5. The enzyme's activity is essential for cell proliferation since adequate levels of pyrimidine nucleotides are critical for DNA replication and cell division.

Review Questions

• What role does orotate phosphoribosyltransferase play in the synthesis of pyrimidine nucleotides?
  • Orotate phosphoribosyltransferase catalyzes the reaction between orotate and 5-phosphoribosyl-1-pyrophosphate (PRPP), resulting in the formation of orotidine monophosphate (OMP). This reaction is a crucial step in the de novo synthesis pathway for pyrimidine nucleotides. By facilitating this conversion, the enzyme ensures that sufficient levels of OMP are available for further metabolism into uridine monophosphate (UMP) and other pyrimidine nucleotides.
• Discuss the implications of orotate phosphoribosyltransferase deficiency on human health.
  • Deficiency in orotate phosphoribosyltransferase can result in a condition known as orotic aciduria, characterized by excessive excretion of orotic acid in urine. This disorder can lead to various health issues such as megaloblastic anemia due to impaired DNA synthesis. Since pyrimidine nucleotides are vital for cellular functions, individuals with this deficiency may experience growth retardation and other developmental problems as a result of disrupted nucleotide availability.
• Evaluate how targeting orotate phosphoribosyltransferase could be beneficial in cancer therapy.
  • Targeting orotate phosphoribosyltransferase presents a strategic approach in cancer therapy by inhibiting nucleotide synthesis pathways essential for rapidly dividing cancer cells. By limiting the availability of pyrimidine nucleotides needed for DNA replication, inhibitors of this enzyme can effectively reduce tumor growth. This mechanism highlights the potential for developing specific pharmacological agents that could disrupt cancer cell proliferation while sparing normal cells, enhancing treatment efficacy and minimizing side effects.

Related terms

5-Phosphoribosyl-1-pyrophosphate (PRPP): A crucial intermediate in the synthesis of nucleotides, PRPP serves as a ribose donor in various biosynthetic reactions, including those for purines and pyrimidines.

Orotidine monophosphate (OMP): A pyrimidine nucleotide that is produced from orotate and PRPP through the action of orotate phosphoribosyltransferase, serving as a precursor to uridine monophosphate (UMP).

Pyrimidine biosynthesis: The metabolic pathway responsible for the synthesis of pyrimidine nucleotides, which includes uracil, cytosine, and thymine, essential for DNA and RNA synthesis.