1. Naturally-occurring and synthetic analogues of
phenylalanine,
tyrosine,
histidine,
arginine,
proline,
tryptophan and the sulphur
amino acids have beeen tested in rat reticulocytes and in the Reuber H35
hepatoma for effects on
protein synthesis and protein degradation and on the heat lability of
phosphoenolpyruvate carboxykinase (EC 4.1.1.32) in the
hepatoma cells. The experiments were designed to test whether the analogues could be incorporated into mammalian
proteins and whether the resultant
proteins would be degraded at an accelerated rate. 2. Several analogues, including thiazolylanine, triazolalanine and
selenocystine both stimulated
protein synthesis and produced labile
protein in reticulocytes. Other analogues, such as
dihydroxyphenylalanine,
thioproline and
pipecolic acid accelerated
protein breakdown but probably indirectly via an inhibition of
protein synthesis.
Azetidine-2-carboxylic acid had the largest effect on
protein breakdown in reticulocytes. 3. Labile
protein was produced in
hepatoma cells incubated in the presence of
azetidine-2-carboxylic acid,
canavanine,
indospicine, triazolalanine, 2-, 3- and
4-fluorophenylalanine. These same analogues, together with
3,4-dehydroproline, beta-2-thienylalanine,
dihydroxyphenylalanine,
histidinol, 5- and
6-fluorotryptophan,
selenocystine and
selenomethionine produced heat-labile
phosphoenolpyruvate carboxykinase.
Enzyme induced in the presence of
selenomethionine or
indospicine showed the largest increases in heat lability, and for these analogues equimolar concentrations of
methionine and
arginine respectively were needed to nullify the
enzyme abnormality. 4. The toxicity of the same naturally-occurring analogues has been discussed in terms of their ability to be incorporated into cell
proteins.