Inhibition by a nonmetabolized analogue of L-leucine of protein biosynthesis in tumoral pancreatic islet cells.
The effect of L-leucine, its deaminated metabolite 2-ketoisocaproate and its nonmetabolized analogue b(+/-)2-aminobicyclo[2,2,1]-heptane-2-carboxylic acid (BCH) upon protein labelling was examined in tumoral islet cells (RINm5F line) exposed to L-[4-3H]phenylalanine or L-[3-3H]serine. The interpretation of the results, in terms of changes in biosynthetic activity, was obscured by a possible interference of the tested nutrients with the uptake and further metabolism of the tracer tritiated amino acids. Nevertheless, when the cells were preincubated with the nutrient secretagogues and then incubated in the sole presence of L-[3-3H]serine, BCH, but not L-leucine or 2-ketoisocaproate, still inhibited protein labelling, this coinciding with a decrease in the ratio between TCA-precipitable and total radioactivity in the RINm5F cells. The inhibitory action of BCH was antagonized, to a limited extent, by D-glucose. It is proposed that BCH could be used as a tool to interfere with the function and growth of insulinoma cells.
Barreto
M
M
Fundación Jiménez Díaz, Centro Asociado al Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
Sener
A
A
Malaisse
W J
WJ
Valverde
I
I
D007516:Adenoma, Islet Cell / Q000378:metabolism*; D000596:Amino Acids / Q000494:pharmacology; D000598:Amino Acids, Cyclic; D007651:Keto Acids / Q000494:pharmacology; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000187:drug effects*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010649:Phenylalanine / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D007651:Keto Acids; D009363:Neoplasm Proteins; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; D012694:Serine; D010649:Phenylalanine; C013082:alpha-ketoisocaproic acid; D007930:Leucine