Protein methylase III (S-adenosylmethionine:proteinlysine methyltransferase; ED 
2.1.1.25) and protein methylase I (S-adenosylmethionine:protein-arginine 
methyltransferase; EC 2.1.1.23) activities were examined in isolated nuclei and 
cytosol fraction, respectively, from various hepatomas with different growth 
rates. The enzyme activities of both enzymes paralleled the rates of tumor 
growth in fast- and moderately growing hepatomas. The parallelism was more 
evident with protein methylase I than with protein methylase III. While protein 
methylase III activity was elevated in the fast- to moderately growing 
hepatomas, the enzyme that is responsible for demethylating proteins, 
epsilon-alkyllysinase (epsilon-slkyl-L-lysine:oxygen oxidoreductase; EC 
1.5.3.4), had an inverse relationship to the rate of tumor growth, thus 
suggesting a possible physiological antagonism. When isolated rat liver nuclei 
were methylated in vitro with S-adenosyl-L-[methyl-14 C]methionine as methyl 
donor, H2SO4-insoluble protein and histones had almost equal amounts of 
methyl-14 C incorporated. However, amino acid analysis revealed that methylated 
arginines are the predominant form of radioactivity in the H2SO4-insoluble 
protein (product of protein methylase I), while methylated lysines are the major 
methylated amino acids in the histones (product of protein methylase III). 
Furthermore, the hydrolysate of the H2SO4-insoluble protein showed four unknown 
radioactivity peaks on the amino acid analyzer in addition to the known 
methylated arginine and lysine derivatives.