Intestinal ornithine decarboxylase: half-life and regulation by putrescine.
Ornithine decarboxylase (ODC) is the primary rate-limiting enzyme for polyamine synthesis. ODC levels are increased in most tissues, including the intestinal mucosa, by growth-promoting agents. This enzyme has a brief half-life of from 5 to 30 min in mammalian tissues and is regulated by its product; putrescine. The current study examines the turnover and regulation of ODC in the mucosa of the small intestine. With the use of scraped intestinal mucosa from cycloheximide-treated rats, the time course of the decline in ODC activity yielded a half-life of approximately 22 min. Labeling enzyme protein with [3H]difluoromethylornithine (DFMO) resulted in a nearly identical estimation of half-life. ODC activity of mucosa from isolated gut segments stimulated by luminal glycine (0.1-0.4 M) was enhanced 60-100% by 10 mM putrescine administered luminally. Putrescine alone had no effect on ODC. In contrast, 10(-7) M putrescine prevented 80% of the ODC activity stimulated by asparagine in IEC-6 cells (a rat intestinal crypt cell line). The half-life of ODC in unstimulated IEC-6 cells was 20 min and increased to 35 min in cells exposed to 10 mM asparagine. These data demonstrate that ODC of nonproliferating villous cells is regulated differently from the identical enzyme in proliferating crypt cells. Therefore, conclusions regarding mucosal growth should not be based totally on ODC activity from whole mucosa, since it is essentially a measure of only the enzyme present in the villous cells.
Iwami
K
K
Department of Physiology and Cell Biology, University of Texas Medical School, Houston 77030.
Wang
J Y
JY
Jain
R
R
McCormack
S
S
Johnson
L R
LR
D000818:Animals; D001216:Asparagine / Q000494:pharmacology; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D000518:Eflornithine / Q000378:metabolism; D006706:Homeostasis; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011485:Protein Binding; D011700:Putrescine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D001216:Asparagine; D003513:Cycloheximide; D009955:Ornithine Decarboxylase; D011700:Putrescine; D000518:Eflornithine