title: Guide molecule-driven stereospecific degradation of alpha-methylpolyamines by polyamine oxidase.
abstract: 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.
authors.affiliation: A. I. Virtanen Institute for Molecular Sciences, Kuopio, Finland.
authors.forename: Aki
authors.initials: A
authors.lastname: Järvinen
authors.forename: Tuomo A
authors.initials: TA
authors.lastname: Keinänen
authors.forename: Nikolay A
authors.initials: NA
authors.lastname: Grigorenko
authors.forename: Alex R
authors.initials: AR
authors.lastname: Khomutov
authors.forename: Anne
authors.initials: A
authors.lastname: Uimari
authors.forename: Jouko
authors.initials: J
authors.lastname: Vepsäläinen
authors.forename: Ale
authors.initials: A
authors.lastname: Närvänen
authors.forename: Leena
authors.initials: L
authors.lastname: Alhonen
authors.forename: Juhani
authors.initials: J
authors.lastname: Jänne
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000818:Animals; D001547:Benzaldehydes / Q000737:chemistry; D002021:Buffers; D002244:Carbon / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008956:Models, Chemical; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry; D011073:Polyamines / Q000737:chemistry*; D011485:Protein Binding; D020033:Protein Isoforms; D011700:Putrescine / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D011730:Pyridoxal / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000737:chemistry; D013095:Spermidine / Q000031:analogs & derivatives / Q000737:chemistry; D013237:Stereoisomerism; D013379:Substrate Specificity; D000097667:Polyamine Oxidase
chemical_list: D000447:Aldehydes; D001547:Benzaldehydes; D002021:Buffers; D002244:Carbon; D000587:Oxidoreductases Acting on CH-NH Group Donors; D010100:Oxygen; D011073:Polyamines; D020033:Protein Isoforms; D011700:Putrescine; D011725:Pyridines; D011730:Pyridoxal; D011994:Recombinant Proteins; D013095:Spermidine; D000097667:Polyamine Oxidase; C509913:1-amino-8-acetamido-5-azanonane; C017988:N(1)-acetylspermidine; C051439:pyridinecarboxaldehyde; C032175:benzaldehyde