Characterization of a defect in the pathway for converting 5'-deoxy-5'-methylthioadenosine to methionine in a subline of a cultured heterogeneous human colon carcinoma.
5'-Deoxy-5'-methylthioadenosine (methylthioadenosine) is cleaved to adenine and 5-methylthioribose-1-phosphate (methylthioribose-1-P). Methylthioribose-1-P is converted to 2-keto-4-methylthiobutyrate ( ketomethylthiobutyrate ) which is transaminated to methionine. We report that one subline of a heterogeneous human colon carcinoma, DLD-1 Clone D, only forms methylthioribose-1-P from methylthioadenosine or 5'-deoxy-5'-methylthioinosine (methylthioinosine), a deaminated derivative of methylthioadenosine, whereas Clone A converts methylthioadenosine and methylthioinosine to methionine, as shown by growth studies in culture of Clone A and Clone D cells and radioactive studies utilizing [methyl-14C]methylthioadenosine or [methyl-14C]methylthioinosine in the presence of extracts of these cells lines. To characterize this defect, we utilized three protein fractions isolated from rat liver which together convert methylthioribose-1-P to ketomethylthiobutyrate . Addition of only Fraction A to Clone D sonicates restores its ability to convert methylthioadenosine to methionine. This fraction is responsible for converting methylthioribose-1-P to 5- methylthioribulose -1-phosphate; radioactive studies confirm this observation. Thus, Clone D is deficient in an enzyme contained in Fraction A; this represents a qualitative biochemical difference between the two clones derived from a single human tumor.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003110:Colonic Neoplasms / Q000378:metabolism*; D003839:Deoxyadenosines; D006801:Humans; D008099:Liver / Q000378:metabolism; D008715:Methionine / Q000378:metabolism*; D051381:Rats; D012267:Ribosemonophosphates / Q000378:metabolism; D012274:Ribulosephosphates / Q000378:metabolism; D013865:Thioglycosides / Q000378:metabolism; D013872:Thionucleosides / Q000378:metabolism*
C023029:5'-methylthioribose 1-phosphate; D003839:Deoxyadenosines; D012267:Ribosemonophosphates; D012274:Ribulosephosphates; D013865:Thioglycosides; D013872:Thionucleosides; C008500:5'-methylthioadenosine; C038238:1-phospho-5-S-methylthioribulose; D008715:Methionine; D000241:Adenosine