Amidophosphoribosyltransferase (ATase)

Synonyms: ATase, glutamine phosphoribosylpyrophosphate amidotransferase, GPAT, PRPP-amidotransferase

Luca Fischer

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Luca Fischer

1. Definition

The amidophosphoribosyltransferase (ATase) is an enzyme, which catalyzes the formation of 5-phosphoribosyl-1-amine (PRA) from 5-phosphoribosyl-1-pyrophosphate (PRPP) and glutamine by splitting off pyrophosphate and glutamate. This is the rate-limiting step of de novo purine synthesis. In humans it is encoded by the PPAT (phosphoribosyl pyrophosphate amidotransferase) gene.

2. Biochemistry

The ATase is located in the cytosol and uses magnesium and an iron-sulfur cluster as cofactors.

It consists of two domains: a glutaminase domain that produces ammonia from glutamine by hydrolysis and a phosphoribosyltransferase domain that binds the ammonia to ribose-5-phosphate.

Regulation of the enzyme mainly happens through feedback-inhibition. So the ATase is inhibited by the end-products of the purine synthesis pathway, AMP, GMP, ADP, and GDP.

3. Reaction mechanism

The overall reaction catalyzed by ATase is the following:

PRPP + glutamine → PRA + glutamate + PPi

Within the enzyme, the reaction is broken down into two half-reactions that occur at different active sites:

glutamine → NH₃ + glutamate
PRPP + NH₃ → PRA + PPi

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Specialty

Biochemistry

Keywords

Last edit:

2025-01-30 21:54:16

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Amidophosphoribosyltransferase (ATase)

Luca Fischer

Table of Contents

1. Definition

2. Biochemistry

3. Reaction mechanism

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