APRT Human

Adenine Phosphoribosyltransferase (APRT) is an enzyme encoded by the APRT gene, located on chromosome 16 in humans . This enzyme plays a crucial role in the purine salvage pathway, which is essential for recycling purines to synthesize nucleotides efficiently .

APRT belongs to the Type I Phosphoribosyltransferase (PRTase) family . The enzyme catalyzes the transfer of a phosphoribosyl group from phosphoribosyl pyrophosphate (PRPP) to adenine, forming adenosine monophosphate (AMP) and pyrophosphate (PPi) . The reaction can be summarized as follows:

$$\text{Adenine} + \text{PRPP} \rightarrow \text{AMP} + \text{PPi}$$

This reaction is vital for the nucleotide salvage pathway, providing an alternative to the energetically expensive de novo synthesis of nucleotides .

APRT is present in all tissues and is the only known mechanism for the metabolic salvage of adenine derived from polyamine biosynthesis or dietary sources . In parasitic protozoa, such as Giardia, APRT provides the sole mechanism for AMP production .

APRT deficiency can lead to serious kidney conditions, including nephrolithiasis (kidney stones), interstitial nephritis, and chronic renal failure . This is due to the precipitation of 2,8-dihydroxyadenine (DHA) crystals in the renal interstitium . Understanding the structure and function of APRT is crucial for developing treatments for these conditions.

Human recombinant APRT is produced using Escherichia coli as an expression system . The recombinant enzyme has been crystallized and studied using X-ray diffraction, revealing a structure composed of nine beta-strands and six alpha-helices . The active site pocket of APRT opens slightly to accommodate the AMP product, and structural comparisons with other PRTases have provided insights into the enzyme’s specificity and function .