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adenosylmethionine decarboxylase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: S-adenosyl-L-methionine + H+ = S-adenosylmethioninamine + CO2. [EC:4.1.1.50, RHEA:15981]

Adenosylmethionine decarboxylase (AMDase) activity is a critical step in the biosynthesis of polyamines, small, organic molecules essential for cell growth, proliferation, and differentiation. The enzyme catalyzes the removal of carbon dioxide from S-adenosyl-L-methionine (SAM), producing decarboxylated SAM (dcSAM). This reaction is the committed step in polyamine biosynthesis and is tightly regulated to ensure appropriate polyamine levels within the cell.

AMDase is a pyruvoyl-dependent enzyme, meaning it requires a covalently bound pyruvate molecule for activity. This pyruvate molecule acts as a prosthetic group, participating directly in the decarboxylation reaction.

The reaction mechanism involves the following steps:

1. SAM binds to the active site of AMDase.
2. The pyruvate group of AMDase abstracts a proton from the C-5' carbon of SAM.
3. This proton abstraction facilitates the decarboxylation of SAM, resulting in the formation of dcSAM and carbon dioxide.
4. The decarboxylated product, dcSAM, is released from the enzyme.

The decarboxylated SAM (dcSAM) produced by AMDase is a substrate for spermidine synthase, which catalyzes the transfer of the aminopropyl group from dcSAM to putrescine, forming spermidine. Spermidine is then used to synthesize spermine, another essential polyamine.

Dysregulation of AMDase activity has been linked to various pathological conditions, including cancer, neurodegenerative disorders, and inflammatory diseases. Therefore, AMDase is considered a promising drug target for the treatment of these diseases.
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Proteins (2)

ProteinDefinitionTaxonomy
S-adenosylmethionine decarboxylase proenzymeA SAM decarboxylase proenzyme that is encoded in the genome of human. [PRO:DNx, UniProtKB:P17707]Homo sapiens (human)
S-adenosylmethionine decarboxylase proenzymeA SAM decarboxylase proenzyme that is encoded in the genome of human. [PRO:DNx, UniProtKB:P17707]Homo sapiens (human)

Compounds (2)

CompoundDefinitionClassesRoles
putrescinealkane-alpha,omega-diamineantioxidant;
fundamental metabolite
mitoguazonemitoguazone : A hydrazone obtained by formal condensation of the two carbonyl groups of methylglyoxal with the primary amino groups of two molecules of aminoguanidine.

Mitoguazone: Antineoplastic agent effective against myelogenous leukemia in experimental animals. Also acts as an inhibitor of animal S-adenosylmethionine decarboxylase.
guanidines;
hydrazone
antineoplastic agent;
apoptosis inducer;
EC 4.1.1.50 (adenosylmethionine decarboxylase) inhibitor