RGD Reference Report - Guide molecule-driven stereospecific degradation of alpha-methylpolyamines by polyamine oxidase. - Rat Genome Database
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Guide molecule-driven stereospecific degradation of alpha-methylpolyamines by polyamine oxidase.

Authors: Järvinen, Aki  Keinänen, Tuomo A  Grigorenko, Nikolay A  Khomutov, Alex R  Uimari, Anne  Vepsäläinen, Jouko  Närvänen, Ale  Alhonen, Leena  Jänne, Juhani 
Citation: Järvinen A, etal., J Biol Chem. 2006 Feb 24;281(8):4589-95. Epub 2005 Dec 14.
RGD ID: 12790650
Pubmed: (View Article at PubMed) PMID:16354669
DOI: Full-text: DOI:10.1074/jbc.M509959200

FAD-dependent polyamine oxidase (PAO; EC 1.5.3.11) is one of the key enzymes in the catabolism of polyamines spermidine and spermine. The natural substrates for the enzyme are N1-acetylspermidine, N1-acetylspermine, and N1,N12-diacetylspermine. Here we report that PAO, which normally metabolizes achiral substrates, oxidized (R)-isomer of 1-amino-8-acetamido-5-azanonane and N1-acetylspermidine as efficiently while (S)-1-amino-8-acetamido-5-azanonane was a much less preferred substrate. It has been shown that in the presence of certain aldehydes, the substrate specificity of PAO and the kinetics of the reaction are changed to favor spermine and spermidine as substrates. Therefore, we examined the effect of several aldehydes on the ability of PAO to oxidize different enantiomers of alpha-methylated polyamines. PAO supplemented with benzaldehyde predominantly catalyzed the cleavage of (R)-isomer of alpha-methylspermidine, whereas in the presence of pyridoxal the (S)-alpha-methylspermidine was preferred. PAO displayed the same stereospecificity with both singly and doubly alpha-methylated spermine derivatives when supplemented with the same aldehydes. Structurally related ketones proved to be ineffective. This is the first time that the stereospecificity of FAD-dependent oxidase has been successfully regulated by changing the supplementary aldehyde. These findings might facilitate the chemical regulation of stereospecificity of the enzymes.

Annotation

Gene Ontology Annotations    

Biological Process

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Paox  (polyamine oxidase)


Additional Information