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5-phosphoribosyl-1-amine (PRA)

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Biological Chemistry II

Definition

5-phosphoribosyl-1-amine (PRA) is an important intermediate in the de novo biosynthesis of purines. It is formed from 5-phosphoribosyl-1-pyrophosphate (PRPP) through the action of the enzyme amidophosphoribosyltransferase, marking a critical step in the pathway that synthesizes purine nucleotides such as ATP and GTP, essential for cellular functions.

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5 Must Know Facts For Your Next Test

  1. PRA is synthesized from PRPP in a reaction catalyzed by amidophosphoribosyltransferase, making it a key regulator of purine synthesis.
  2. The formation of PRA marks the first committed step in the purine biosynthetic pathway, leading to the production of adenine and guanine nucleotides.
  3. PRA can undergo further transformations to eventually yield important molecules like inosine monophosphate (IMP), which is a precursor for all purine nucleotides.
  4. PRA levels can influence the overall rate of purine biosynthesis, reflecting the cell's demand for energy and nucleotides based on metabolic needs.
  5. Defects in purine metabolism involving PRA can lead to various metabolic disorders, emphasizing its importance in maintaining cellular function.

Review Questions

  • How does 5-phosphoribosyl-1-amine fit into the overall pathway of purine biosynthesis?
    • 5-phosphoribosyl-1-amine (PRA) serves as a crucial intermediate in the de novo synthesis of purines. It is formed from PRPP through the action of amidophosphoribosyltransferase, marking the first committed step in this biosynthetic pathway. From PRA, several enzymatic reactions lead to the production of key purine nucleotides like IMP, which are vital for DNA and RNA synthesis and energy metabolism.
  • Discuss the significance of amidophosphoribosyltransferase in the context of PRA production and purine metabolism.
    • Amidophosphoribosyltransferase is essential for converting PRPP into 5-phosphoribosyl-1-amine (PRA), thus playing a pivotal role in purine metabolism. This enzyme's activity determines the flux through the purine biosynthetic pathway, influencing how efficiently cells can synthesize nucleotides. Regulation of this enzyme ensures that nucleotide synthesis matches cellular demands, preventing imbalances that could lead to metabolic disorders.
  • Evaluate how disruptions in PRA metabolism might impact cellular function and health.
    • Disruptions in the metabolism of 5-phosphoribosyl-1-amine (PRA) can severely affect cellular function due to their impact on purine nucleotide levels. If PRA synthesis or subsequent reactions are impaired, it could lead to reduced availability of ATP and GTP, crucial for energy transfer and signaling within cells. This disruption can manifest in various metabolic disorders, affecting cell proliferation and function, particularly in rapidly dividing tissues such as bone marrow or cancer cells.

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