Putrescine biosynthesis in mammalian tissues

Catherine S. Coleman, Guirong Hu, Anthony E. Pegg

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

L-Ornithine decarboxylase provides de novo putrescine biosynthesis in mammals. Alternative pathways to generate putrescine that involve ADC (L-arginine decarboxylase) occur in non-mammalian organisms. It has been suggested that an ADC-mediated pathway may generate putrescine via agmatine in mammalian tissues. Published evidence for a mammalian ADC is based on (i) assays using mitochondrial extracts showing production of 14CO2 from [1-14C]arginine and (ii) cloned cDNA sequences that have been claimed to represent ADC. We have reinvestigated this evidence and were unable to find any evidence supporting a mammalian ADC. Mitochondrial extracts prepared from freshly isolated rodent liver and kidney using a metrizamide/Percoll density gradient were assayed for ADC activity using L-[U-14C]- arginine in the presence or absence of arginine metabolic pathway inhibitors. Although 14CO2 was produced in substantial amounts, no labelled agmatine or putrescine was detected. [14C]Agmatine added to liver extracts was not degraded significantly indicating that any agmatine derived from a putative ADC activity was not lost due to further metabolism. Extensive searches of current genome databases using non-mammalian ADC sequences did not identify a viable candidate ADC gene. One of the putative mammalian ADC sequences appears to be derived from bacteria and the other lacks several residues that are essential for decarboxylase activity. These results indicate that 14CO2 release from [1-14C]arginine is not adequate evidence for a mammalian ADC. Although agmatine is a known constituent of mammalian cells, it can be transported from the diet. Therefore L-ornithine decarboxylase remains the only established route for de novo putrescine biosynthesis in mammals.

Original languageEnglish (US)
Pages (from-to)849-855
Number of pages7
JournalBiochemical Journal
Volume379
Issue number3
DOIs
StatePublished - May 1 2004

Fingerprint

Putrescine
Biosynthesis
Arginine
Tissue
Agmatine
Mammals
Ornithine Decarboxylase
arginine decarboxylase
Genes
Metrizamide
Liver Extracts
Carboxy-Lyases
Nutrition
Metabolic Networks and Pathways
Metabolism
Liver

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Coleman, Catherine S. ; Hu, Guirong ; Pegg, Anthony E. / Putrescine biosynthesis in mammalian tissues. In: Biochemical Journal. 2004 ; Vol. 379, No. 3. pp. 849-855.
@article{4cf267f3056d414d8d616173803fee5e,
title = "Putrescine biosynthesis in mammalian tissues",
abstract = "L-Ornithine decarboxylase provides de novo putrescine biosynthesis in mammals. Alternative pathways to generate putrescine that involve ADC (L-arginine decarboxylase) occur in non-mammalian organisms. It has been suggested that an ADC-mediated pathway may generate putrescine via agmatine in mammalian tissues. Published evidence for a mammalian ADC is based on (i) assays using mitochondrial extracts showing production of 14CO2 from [1-14C]arginine and (ii) cloned cDNA sequences that have been claimed to represent ADC. We have reinvestigated this evidence and were unable to find any evidence supporting a mammalian ADC. Mitochondrial extracts prepared from freshly isolated rodent liver and kidney using a metrizamide/Percoll density gradient were assayed for ADC activity using L-[U-14C]- arginine in the presence or absence of arginine metabolic pathway inhibitors. Although 14CO2 was produced in substantial amounts, no labelled agmatine or putrescine was detected. [14C]Agmatine added to liver extracts was not degraded significantly indicating that any agmatine derived from a putative ADC activity was not lost due to further metabolism. Extensive searches of current genome databases using non-mammalian ADC sequences did not identify a viable candidate ADC gene. One of the putative mammalian ADC sequences appears to be derived from bacteria and the other lacks several residues that are essential for decarboxylase activity. These results indicate that 14CO2 release from [1-14C]arginine is not adequate evidence for a mammalian ADC. Although agmatine is a known constituent of mammalian cells, it can be transported from the diet. Therefore L-ornithine decarboxylase remains the only established route for de novo putrescine biosynthesis in mammals.",
author = "Coleman, {Catherine S.} and Guirong Hu and Pegg, {Anthony E.}",
year = "2004",
month = "5",
day = "1",
doi = "10.1042/BJ20040035",
language = "English (US)",
volume = "379",
pages = "849--855",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "3",

}

Putrescine biosynthesis in mammalian tissues. / Coleman, Catherine S.; Hu, Guirong; Pegg, Anthony E.

In: Biochemical Journal, Vol. 379, No. 3, 01.05.2004, p. 849-855.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Putrescine biosynthesis in mammalian tissues

AU - Coleman, Catherine S.

AU - Hu, Guirong

AU - Pegg, Anthony E.

PY - 2004/5/1

Y1 - 2004/5/1

N2 - L-Ornithine decarboxylase provides de novo putrescine biosynthesis in mammals. Alternative pathways to generate putrescine that involve ADC (L-arginine decarboxylase) occur in non-mammalian organisms. It has been suggested that an ADC-mediated pathway may generate putrescine via agmatine in mammalian tissues. Published evidence for a mammalian ADC is based on (i) assays using mitochondrial extracts showing production of 14CO2 from [1-14C]arginine and (ii) cloned cDNA sequences that have been claimed to represent ADC. We have reinvestigated this evidence and were unable to find any evidence supporting a mammalian ADC. Mitochondrial extracts prepared from freshly isolated rodent liver and kidney using a metrizamide/Percoll density gradient were assayed for ADC activity using L-[U-14C]- arginine in the presence or absence of arginine metabolic pathway inhibitors. Although 14CO2 was produced in substantial amounts, no labelled agmatine or putrescine was detected. [14C]Agmatine added to liver extracts was not degraded significantly indicating that any agmatine derived from a putative ADC activity was not lost due to further metabolism. Extensive searches of current genome databases using non-mammalian ADC sequences did not identify a viable candidate ADC gene. One of the putative mammalian ADC sequences appears to be derived from bacteria and the other lacks several residues that are essential for decarboxylase activity. These results indicate that 14CO2 release from [1-14C]arginine is not adequate evidence for a mammalian ADC. Although agmatine is a known constituent of mammalian cells, it can be transported from the diet. Therefore L-ornithine decarboxylase remains the only established route for de novo putrescine biosynthesis in mammals.

AB - L-Ornithine decarboxylase provides de novo putrescine biosynthesis in mammals. Alternative pathways to generate putrescine that involve ADC (L-arginine decarboxylase) occur in non-mammalian organisms. It has been suggested that an ADC-mediated pathway may generate putrescine via agmatine in mammalian tissues. Published evidence for a mammalian ADC is based on (i) assays using mitochondrial extracts showing production of 14CO2 from [1-14C]arginine and (ii) cloned cDNA sequences that have been claimed to represent ADC. We have reinvestigated this evidence and were unable to find any evidence supporting a mammalian ADC. Mitochondrial extracts prepared from freshly isolated rodent liver and kidney using a metrizamide/Percoll density gradient were assayed for ADC activity using L-[U-14C]- arginine in the presence or absence of arginine metabolic pathway inhibitors. Although 14CO2 was produced in substantial amounts, no labelled agmatine or putrescine was detected. [14C]Agmatine added to liver extracts was not degraded significantly indicating that any agmatine derived from a putative ADC activity was not lost due to further metabolism. Extensive searches of current genome databases using non-mammalian ADC sequences did not identify a viable candidate ADC gene. One of the putative mammalian ADC sequences appears to be derived from bacteria and the other lacks several residues that are essential for decarboxylase activity. These results indicate that 14CO2 release from [1-14C]arginine is not adequate evidence for a mammalian ADC. Although agmatine is a known constituent of mammalian cells, it can be transported from the diet. Therefore L-ornithine decarboxylase remains the only established route for de novo putrescine biosynthesis in mammals.

UR - http://www.scopus.com/inward/record.url?scp=2542527672&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2542527672&partnerID=8YFLogxK

U2 - 10.1042/BJ20040035

DO - 10.1042/BJ20040035

M3 - Article

C2 - 14763899

AN - SCOPUS:2542527672

VL - 379

SP - 849

EP - 855

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 3

ER -