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...
Saved in:
Published in | Biochimica et biophysica acta Vol. 1723; no. 1; pp. 74 - 81 |
---|---|
Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier B.V
25.05.2005
Elsevier |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 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. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0304-4165 0006-3002 1872-8006 |
DOI: | 10.1016/j.bbagen.2005.01.001 |