guanine salvage

Definition

Target type: biologicalprocess

Any process that generates guanine, 2-amino-6-hydroxypurine, from derivatives of it without de novo synthesis. [GOC:jl]

Guanine salvage is a metabolic pathway that recovers guanine, a purine base, from degraded nucleic acids and other sources to synthesize new guanine nucleotides. This process is essential for maintaining cellular guanine nucleotide pools, which are vital for DNA replication, RNA transcription, and other cellular processes.

The guanine salvage pathway begins with the uptake of guanine from the extracellular environment or from the breakdown of cellular nucleic acids. Once inside the cell, guanine is converted to guanosine monophosphate (GMP) through a two-step enzymatic reaction.

The first step involves the phosphorylation of guanine to guanosine by the enzyme guanine phosphoribosyltransferase (GPRT). GPRT utilizes phosphoribosyl pyrophosphate (PRPP) as a donor of the phosphoribosyl group, which is attached to the guanine molecule to form guanosine.

The second step is the phosphorylation of guanosine to GMP, catalyzed by the enzyme nucleoside monophosphate kinase. This reaction uses ATP as a phosphate donor, transferring a phosphate group from ATP to the 5'-hydroxyl group of guanosine to produce GMP.

GMP is then utilized for the synthesis of other guanine nucleotides, such as GDP and GTP, through a series of enzymatic reactions. These reactions involve the addition of phosphate groups to GMP by kinases. GDP is formed by the phosphorylation of GMP by guanylate kinase, while GTP is formed by the phosphorylation of GDP by nucleoside diphosphate kinase.

Guanine salvage is a crucial process for cell survival and proliferation. By recovering guanine from degraded nucleic acids, the pathway conserves cellular energy and reduces the need for de novo purine biosynthesis, which is a more energy-intensive process.

Defects in the guanine salvage pathway can lead to various genetic diseases. For example, mutations in the GPRT gene can cause Lesch-Nyhan syndrome, a severe neurodevelopmental disorder characterized by self-injurious behavior, hyperuricemia, and gout. Deficiency in other enzymes involved in the guanine salvage pathway can also lead to various metabolic disorders.'
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Proteins (1)

Compounds (11)