Ribose-phosphate diphosphokinase

Ribose-phosphate diphosphokinase is an enzyme that plays a crucial role in the biosynthesis of nucleotides, the building blocks of DNA and RNA. This enzyme catalyzes the conversion of Ribose 5-phosphate (R5P) and Adenosine triphosphate (ATP) to 5-Phosphoribosyl 1-pyrophosphate (PRPP) and Adenosine diphosphate (ADP), a key step in the Pentose phosphate pathway and the de novo synthesis of purine and pyrimidine nucleotides.

Function

Ribose-phosphate diphosphokinase is essential for the production of PRPP, a precursor molecule for the synthesis of nucleotides. PRPP is involved not only in nucleotide biosynthesis but also in several other metabolic pathways, including the salvage pathways of nucleotide synthesis, where it serves as a substrate for the synthesis of nucleoside monophosphates from free bases.

Structure

The enzyme is composed of multiple subunits, which may vary among different organisms. Its structure is critical for its function, as the active site must correctly align R5P and ATP for the reaction to proceed efficiently.

Mechanism

The enzyme catalyzes the transfer of a pyrophosphate group from ATP to the 1'-hydroxyl group of R5P, forming PRPP and ADP. This reaction is magnesium-dependent and requires the presence of Mg2+ ions for catalysis.

Clinical Significance

Alterations in the activity of ribose-phosphate diphosphokinase can lead to disorders in nucleotide metabolism, impacting both DNA and RNA synthesis. This can result in a variety of clinical manifestations, including immunodeficiency, due to the crucial role of nucleotides in cell division and function.

Genetic Regulation

The gene encoding ribose-phosphate diphosphokinase is regulated by a variety of factors, ensuring that the production of PRPP is tightly controlled according to the cellular demand for nucleotides.

See Also

• Pentose phosphate pathway
• Nucleotide
• DNA
• RNA
• ATP
• ADP

References

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  2h06

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  Phosphoribosyl pyrophosphate synthetase equation

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  Phosphoribosyl pyrophosphate synthetase mechanism

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  One subunit of the enzyme phosphoribosyl pyrophosphate synthase I (human)

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  Homodimer of phosphoribosyl pyrophosphate synthase I (human)