Page last updated: 2024-10-24

S-methyl-5-thioadenosine phosphorylase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: 5'-methylthioadenosine + phosphate = adenine + 5-methylthio-D-ribose 1-phosphate. [EC:2.4.2.28]

S-methyl-5-thioadenosine phosphorylase (MTAP) activity plays a critical role in purine metabolism, specifically in the degradation pathway of S-adenosylmethionine (SAM). SAM is a universal methyl donor involved in numerous cellular processes, including DNA methylation, RNA methylation, and protein methylation. During these processes, SAM is converted to S-methyl-5-thioadenosine (MTA).

MTAP catalyzes the reversible phosphorolysis of MTA, yielding adenine and 5-methylthioribose 1-phosphate. This reaction is essential for maintaining intracellular adenine and ribose pools, both of which are crucial for nucleotide biosynthesis. Additionally, MTAP activity helps to regulate SAM levels and prevent accumulation of MTA, which can be toxic at high concentrations.

The enzyme's function can be described in detail as follows:

1. **Substrate Binding:** MTAP binds to MTA and inorganic phosphate (Pi) at its active site.
2. **Phosphorolysis:** The enzyme catalyzes the cleavage of the glycosidic bond between the adenine base and the ribose moiety of MTA, yielding adenine and 5-methylthioribose 1-phosphate. This reaction is driven by the release of inorganic phosphate.
3. **Product Release:** The products, adenine and 5-methylthioribose 1-phosphate, are released from the active site, allowing the enzyme to bind new substrates and continue the catalytic cycle.

The activity of MTAP is tightly regulated by various factors, including intracellular concentrations of MTA, adenine, and Pi. Additionally, MTAP is known to be inhibited by certain drugs and metabolites, highlighting its potential as a drug target. Notably, MTAP deficiency is associated with various diseases, including cancer, emphasizing its importance in cellular homeostasis and health.'
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Proteins (1)

ProteinDefinitionTaxonomy
S-methyl-5'-thioadenosine phosphorylaseAn S-methyl-5-thioadenosine phosphorylase that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q13126]Homo sapiens (human)

Compounds (4)

CompoundDefinitionClassesRoles
5'-deoxy-5'-s-isobutylthioadenosine5'-deoxy-5'-S-isobutylthioadenosine: considered an analog of S-adenosylhomocysteine; structure
5'-methylthioadenosine5'-methylthioadenosine: structure

5'-S-methyl-5'-thioadenosine : Adenosine with the hydroxy group at C-5' substituted with a methylthio (methylsulfanyl) group.
thioadenosinealgal metabolite;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
5'-deoxyadenosine5'-deoxyadenosine : A 5'-deoxyribonucleoside compound having adenosine as the nucleobase.

5'-deoxyadenosine: main heading DEOXYADENOSINE refers to the 3' cpd
5'-deoxyribonucleoside;
adenosines
Escherichia coli metabolite;
human metabolite;
mouse metabolite
methylthio-dadme-immucillin-a