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. © 2005 Elsevier B.V. All rights reserved.
Chabanon, H., Aubel, C., Larvaron, P., Villard, C., Carraro, V., & Brachet, P. (2005). Ornithine decarboxylase activity is inhibited by the polyamine precursor amino acids at the protein stability level in Caco-2 cells. Biochimica et Biophysica Acta - General Subjects, 1723(1–3), 74–81. https://doi.org/10.1016/j.bbagen.2005.01.001