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Putrescine biosynthesis in mammalian tissues.
Catherine S Coleman1, Guirong Hu, Anthony E Pegg
1Department of Cellular and Molecular Physiology, The Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, P.O. Box 850, Hershey, PA 17033, USA.
The Biochemical Journal
|February 7, 2004
Summary
Mammalian L-ornithine decarboxylase is the sole source of de novo putrescine. Research found no evidence for L-arginine decarboxylase (ADC) in mammals, refuting previous claims and supporting ODC as the primary pathway.
Area of Science:
- Biochemistry
- Molecular Biology
- Mammalian Metabolism
Background:
- Putrescine is essential for mammalian cell growth and proliferation.
- L-ornithine decarboxylase (ODC) is the established enzyme for de novo putrescine biosynthesis in mammals.
- Alternative pathways involving L-arginine decarboxylase (ADC) exist in non-mammalian organisms, with proposed roles in mammalian tissues.
Purpose of the Study:
- To investigate the existence and activity of L-arginine decarboxylase (ADC) in mammalian systems.
- To re-evaluate the evidence supporting a mammalian ADC pathway for putrescine synthesis.
- To determine the primary route of de novo putrescine biosynthesis in mammals.
Main Methods:
- Assays of mitochondrial extracts from rodent liver and kidney for ADC activity using radiolabeled arginine.
- Inclusion of arginine metabolic pathway inhibitors during enzymatic assays.
- Analysis of potential degradation of radiolabeled agmatine in liver extracts.
- Bioinformatic searches of genome databases for mammalian ADC gene homologues.
- Examination of previously identified putative mammalian ADC sequences.
Main Results:
- No labeled agmatine or putrescine was detected when using L-[U-14C]-arginine as a substrate, despite significant 14CO2 production.
- [14C]Agmatine was not significantly degraded in liver extracts, ruling out rapid metabolism as a cause for lack of detection.
- Genome database searches failed to identify a viable mammalian ADC gene candidate.
- Putative mammalian ADC sequences were identified as bacterial in origin or lacking essential decarboxylase residues.
Conclusions:
- The release of 14CO2 from [1-14C]arginine is insufficient evidence for mammalian ADC activity.
- Agmatine, while present in mammals, can be sourced from dietary intake.
- L-ornithine decarboxylase remains the only confirmed pathway for de novo putrescine biosynthesis in mammals.