Ornithine decarboxylase activity is inhibited by the polyamine precursor amino acids at the protein stability level in Caco-2 cells.
High concentrations of certain amino acids are known to affect hormonal secretion, immune function, electrolyte balance or metabolic functions. However, there is a lack of knowledge regarding the molecular mechanisms responsible for these effects. We showed that, as well as spermidine transport, the activity of ornithine decarboxylase (ODC), the first and rate-limiting enzyme in polyamine biosynthesis, is decreased in human colon adenocarcinoma cells, Caco-2, following a 4-h supplementation with one of the two polyamine precursor amino acids, L-arginine or L-methionine. Dose-response assays indicated that the inhibitory effect of supplemental L-methionine was stronger than that of supplemental L-arginine. However, it was transient, being even replaced by ODC induction after 8 h, whereas the inhibitory effect of L-arginine lasted for at least 8 h. Unlike L-cysteine, neither L-methionine nor L-arginine could inhibit ODC activity in a crude acellular preparation of the enzyme. The inhibition of ODC activity in cells exposed to L-methionine or L-arginine was due to a decreased abundance of ODC protein without change at the mRNA level and each of these amino acids could counteract ODC induction by a glycine supplement. Contrary to the latter, supplemental L-methionine or L-arginine induced a marked decrease in ODC half-life, concomitantly with an increase in the activity of antizyme, an ODC inhibitory protein. Thus, depending on their nature, amino acids can up- or downregulate ODC activity at the protein stability level.
Chabanon
Hervé
H
Centre de Recherche en Nutrition Humaine d'Auvergne, Institut National de la Recherche Agronomique, Theix, 63122 Saint-Genès Champanelle, France.
Aubel
Corinne
C
Larvaron
Pierre
P
Villard
Claude
C
Carraro
Valérie
V
Brachet
Patrick
P
D001120:Arginine / Q000494:pharmacology*; D015317:Biogenic Polyamines / Q000096:biosynthesis*; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D003545:Cysteine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008715:Methionine / Q000494:pharmacology*; D009955:Ornithine Decarboxylase / Q000032:analysis / Q000235:genetics; D065108:Ornithine Decarboxylase Inhibitors; D012333:RNA, Messenger / Q000032:analysis; D013095:Spermidine / Q000378:metabolism
D015317:Biogenic Polyamines; D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; D012333:RNA, Messenger; D001120:Arginine; D008715:Methionine; D009955:Ornithine Decarboxylase; D003545:Cysteine; D013095:Spermidine