key term - Hypoxanthine-guanine phosphoribosyltransferase (hgprt)

Definition

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is an enzyme that plays a crucial role in the purine salvage pathway, which recycles purines from nucleic acid degradation for nucleotide synthesis. This enzyme specifically catalyzes the conversion of hypoxanthine and guanine into their respective nucleotides by transferring a phosphoribosyl group from 5-phosphoribosyl-1-pyrophosphate (PRPP) to these bases, thus preventing their loss and ensuring efficient nucleotide metabolism.

5 Must Know Facts For Your Next Test

1. HGPRT is essential for recycling purines, significantly contributing to the nucleotide pool in cells.
2. Deficiency in HGPRT can lead to Lesch-Nyhan Syndrome, characterized by neurological dysfunction and self-mutilating behaviors.
3. The enzyme specifically facilitates the formation of inosine monophosphate (IMP) from hypoxanthine and guanosine monophosphate (GMP) from guanine.
4. HGPRT helps maintain the balance of purine nucleotides, which is vital for DNA and RNA synthesis.
5. The activity of HGPRT can be influenced by various factors, including substrate availability and cellular demand for nucleotides.

Review Questions

• How does hypoxanthine-guanine phosphoribosyltransferase contribute to nucleotide metabolism?
  • HGPRT contributes to nucleotide metabolism by facilitating the recycling of purines through the purine salvage pathway. It converts hypoxanthine and guanine into their respective nucleotides using PRPP as a donor. This process reduces the reliance on de novo synthesis of purines, making it crucial for maintaining adequate nucleotide levels, especially in cells with high turnover or those that rapidly proliferate.
• Discuss the consequences of HGPRT deficiency on purine metabolism and overall health.
  • HGPRT deficiency leads to impaired purine salvage, causing an increase in uric acid production due to the breakdown of excess purines. This condition results in Lesch-Nyhan Syndrome, which features severe neurological symptoms, self-injurious behaviors, and gout-like manifestations. The lack of HGPRT disrupts normal nucleotide homeostasis, leading to an increased demand for de novo purine synthesis, which cannot keep up with the body's needs, resulting in additional metabolic complications.
• Evaluate the potential therapeutic approaches for managing conditions related to HGPRT deficiency.
  • Therapeutic approaches for managing conditions related to HGPRT deficiency focus on lowering uric acid levels and addressing neurological symptoms. Options include allopurinol, which inhibits xanthine oxidase to decrease uric acid production. Additionally, supportive therapies such as behavioral interventions may help manage self-injurious behaviors associated with Lesch-Nyhan Syndrome. Gene therapy or enzyme replacement therapy are potential future directions that aim to correct or compensate for the underlying enzyme deficiency, although they present significant challenges in practical application.

Related terms

Purine Salvage Pathway: A metabolic pathway that recycles purines and allows the reuse of nucleotides, decreasing the need for de novo synthesis.

5-Phosphoribosyl-1-pyrophosphate (PRPP): A key intermediate in nucleotide synthesis that acts as a donor of the phosphoribosyl group in reactions catalyzed by salvage enzymes like HGPRT.

Lesch-Nyhan Syndrome:

A genetic disorder caused by a deficiency of HGPRT, leading to the accumulation of uric acid and severe neurological and behavioral issues.