Adenine phosphoribosyltransferase

Adenine phosphoribosyltransferase

Adenine phosphoribosyltransferase (APRT) is an enzyme that plays a crucial role in the purine salvage pathway, which is essential for the recycling of purines to synthesize nucleotides. This enzyme catalyzes the conversion of adenine and phosphoribosyl pyrophosphate (PRPP) into adenosine monophosphate (AMP).

Function

APRT is responsible for the salvage of adenine, a purine base, by converting it into AMP. This reaction is important for maintaining the balance of purine nucleotides in the cell and for conserving energy by recycling purines rather than synthesizing them de novo.

Mechanism

The reaction catalyzed by APRT involves the transfer of a phosphoribosyl group from PRPP to adenine, forming AMP and pyrophosphate. This reaction is facilitated by the enzyme's active site, which binds both substrates and stabilizes the transition state.

Reaction scheme of APRTase.

Structure

APRT is a homodimeric enzyme, meaning it consists of two identical subunits. Each subunit contains a flexible loop and a hood domain that are important for substrate binding and catalysis.

Flexible loop and hood domains of human APRTase.

Active Site

The active site of APRT is where adenine and PRPP bind. The enzyme undergoes conformational changes upon substrate binding, which facilitates the catalytic process. The binding site is highly specific for adenine, ensuring the correct substrate is utilized.

Adenine binding site of human APRTase.

Genetic Implications

Mutations in the APRT gene can lead to a deficiency in the enzyme, resulting in the accumulation of adenine and its conversion to 2,8-dihydroxyadenine, which can cause kidney stones and renal failure. This condition is known as APRT deficiency.

Clinical Significance

APRT deficiency is a rare genetic disorder that can lead to the formation of kidney stones composed of 2,8-dihydroxyadenine. Early diagnosis and treatment are important to prevent kidney damage. Treatment typically involves a low-purine diet and medications that reduce adenine production.

Related pages

• Purine metabolism
• Nucleotide salvage
• Adenine
• Phosphoribosyl pyrophosphate

Gallery

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  CpG island of APRT gene.

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  Adenine phosphoribosyltransferase

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  Reaction scheme of APRTase

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  Flexible loop and Hood domains of human APRTase

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  Adenine binding site of human APRTase