Chapter 6. Targeting the Polyamine Catabolic Enzymes Spermine Oxidase, N1-Acetylpolyamine Oxidase and Spermidine/Spermine N1-Acetyltransferase

In addition to polyamine homoeostasis, it has become increasingly clear that polyamine catabolism can play a dominant role in drug response, apoptosis and the response to stressful stimuli, and contribute to the aetiology of several pathological states, including cancer. The highly inducible enzymes SSAT (spermidine/spermine N1-acetyltransferase) and SMO (spermine oxidase) and the generally constitutively expressed APAO (N1-acetylpolyamine oxidase) appear to play critical roles in many normal and disease processes. The dysregulation of polyamine catabolism frequently accompanies several disease states and suggests that such dysregulation may both provide useful insight into disease mechanism and provide unique druggable targets that can be exploited for therapeutic benefit. Each of these enzymes has the potential to alter polyamine homoeostasis in response to multiple cell signals and the two oxidases produce the reactive oxygen species H2O2 and aldehydes, each with the potential to produce pathological states. The activity of SSAT provides substrates for APAO or substrates for the polyamine exporter, thus reducing the intracellular polyamine concentration, the net effect of which depends on the magnitude and rate of any increase in SSAT. SSAT may also influence cellular metabolism via interaction with other proteins and by perturbing the content of acetyl-CoA and ATP. The goal of the present review is to cover those aspects of polyamine catabolism that have an impact on disease aetiology or treatment and to provide a solid background in this ever more exciting aspect of polyamine biology.

Download Full-text

Development of Irreversible Inactivators of Spermine Oxidase and N1-Acetylpolyamine Oxidase

Biological and Pharmaceutical Bulletin ◽

10.1248/bpb.b13-00913 ◽

2014 ◽

Vol 37 (3) ◽

pp. 475-480 ◽

Cited By ~ 4

Author(s):

Shun-suke Moriya ◽

Toshiyuki Miura ◽

Koichi Takao ◽

Yoshiaki Sugita ◽

Keijiro Samejima ◽

...

Keyword(s):

Spermine Oxidase ◽

Acetylpolyamine Oxidase

Download Full-text

The Glu216/Ser218 pocket is a major determinant of spermine oxidase substrate specificity

Biochemical Journal ◽

10.1042/bj20140305 ◽

2014 ◽

Vol 461 (3) ◽

pp. 453-459 ◽

Cited By ~ 9

Author(s):

Manuela Cervelli ◽

Emanuela Angelucci ◽

Pasquale Stano ◽

Loris Leboffe ◽

Rodolfo Federico ◽

...

Keyword(s):

Substrate Specificity ◽

Oxidase Activity ◽

Major Determinant ◽

Spermine Oxidase ◽

Acetylpolyamine Oxidase ◽

Specific Inhibitors

Mutation of spermine oxidase Glu216/Ser218 into the paralogue acetylpolyamine oxidase residues endows spermine oxidase with acetylpolyamine oxidase activity. Glu216 and Ser218 are major determinants of spermine oxidase substrate specificity. This finding will allow for the design of specific inhibitors for these enzymes.

Download Full-text

Identification of Metabolic Routes and Catabolic Enzymes Involved in Phytoremediation of the Nitro- Substituted Explosives TNT, RDX, and HMX

10.21236/ada476298 ◽

2006 ◽

Author(s):

Jong M. Yoon ◽

Jerald L. Schnoor ◽

Benoit Van Aken ◽

Laura B. Brentner ◽

Sachiyo Tanaka ◽

...

Keyword(s):

Catabolic Enzymes

Download Full-text

Consumption of Enriched Yogurt with PAF Inhibitors from Olive Pomace Affects the Major Enzymes of PAF Metabolism: A Randomized, Double Blind, Three Arm Trial

Biomolecules ◽

10.3390/biom11060801 ◽

2021 ◽

Vol 11 (6) ◽

pp. 801

Author(s):

Maria Detopoulou ◽

Agathi Ntzouvani ◽

Filio Petsini ◽

Labrini Gavriil ◽

Εlizabeth Fragopoulou ◽

...

Keyword(s):

Platelet Activating Factor ◽

Lipid Mediator ◽

Olive Pomace ◽

Double Blind ◽

Promising Alternative ◽

Catabolic Enzymes ◽

Platelet Activating Factor Acetylhydrolase ◽

The Impact ◽

By Products ◽

Apparently Healthy

Platelet-activating factor (PAF), a proinflammatory lipid mediator, plays a crucial role in the formation of the atherosclerotic plaque. Therefore, the inhibition of endothelium inflammation by nutraceuticals, such as PAF inhibitors, is a promising alternative for preventing cardiovascular diseases. The aim of the present study was to evaluate the impact of a new functional yogurt enriched with PAF inhibitors of natural origin from olive oil by-products on PAF metabolism. Ninety-two apparently healthy, but mainly overweight volunteers (35–65 years) were randomly allocated into three groups by block-randomization. The activities of PAF’s biosynthetic and catabolic enzymes were measured, specifically two isoforms of acetyl-CoA:lyso-PAF acetyltransferase (LPCATs), cytidine 5′-diphospho-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT) and two isoforms of platelet activating factor acetylhydrolase in leucocytes (PAF-AH) and plasma (lipoprotein associated phospholipase-A2, LpPLA2). The intake of the enriched yogurt resulted in reduced PAF-CPT and LpPLA2 activities. No difference was observed in the activities of the two isoforms of lyso PAF-AT. In conclusion, intake of yogurt enriched in PAF inhibitors could favorably modulate PAF biosynthetic and catabolic pathways.

Download Full-text

DIRECT INDUCTION IN WILD-TYPE NEUROSPORA CRASSA OF MUTANTS (qa-1C) CONSTITUTIVE FOR THE CATABOLISM OF QUINATE AND SHIKIMATE

Genetics ◽

10.1093/genetics/72.3.411 ◽

1972 ◽

Vol 72 (3) ◽

pp. 411-417

Author(s):

C W H Partridge ◽

Mary E Case ◽

Norman H Giles

Keyword(s):

Neurospora Crassa ◽

Single Gene ◽

Ultra Violet ◽

Wild Type ◽

Color Test ◽

Catabolic Enzymes ◽

Direct Induction

ABSTRACT A color test has been developed for the selection and identification of mutants in Neurospora crassa, constitutive for the three normally inducible enzymes which convert quinate to protocatechuate. By this means seven such mutants have been recovered after ultra violet irradiation of wild type and have been shown to be allelic (or very closely linked) to the qa-1C mutants previously obtained by other means. Thus, the regulation of the synthesis of these three catabolic enzymes is indicated to be under the control of a single gene, qa-1+.

Download Full-text