Enzymic imbalance in serine metabolism in human colon carcinoma and rat sarcoma.
The activities of 3-phosphoglycerate dehydrogenase, an enzyme of serine biosynthesis, and serine hydroxymethyltransferase, serine dehydratase and serine aminotransferase, which are competing enzymes of serine utilization, were assayed in human colon carcinomas from patients and in transplantable rat sarcomas. Serine dehydratase and serine aminotransferase activities were absent, whereas 3-phosphoglycerate dehydrogenase and serine hydroxymethyltransferase activities were markedly increased in both tumour types. Serine hydroxymethyltransferase catalyses the formation of glycine and methylene tetrahydrofolate which are important precursors for nucleotide biosynthesis. The observed enzymic imbalance in these tumours ensures that an increased capacity for the synthesis of serine is coupled to its utilisation for nucleotide biosynthesis as a part of the biochemical commitment to cellular replication in cancer cells. That this pattern is found in sarcomas and carcinomas, and in tumours of human and rodent origin, signifies its universal importance for the biochemistry of the cancer cell and singles it out as a potential target site for anti-cancer chemotherapy.
D000368:Aged; D000818:Animals; D002237:Carbohydrate Dehydrogenases / Q000378:metabolism; D003110:Colonic Neoplasms / Q000201:enzymology*; D012696:Glycine Hydroxymethyltransferase / Q000378:metabolism; D006801:Humans; D012695:L-Serine Dehydratase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D050543:Phosphoglycerate Dehydrogenase; D051381:Rats; D011916:Rats, Inbred F344; D012208:Rhabdomyosarcoma / Q000201:enzymology*; D012513:Sarcoma, Experimental / Q000201:enzymology*; D012694:Serine / Q000378:metabolism*; D000637:Transaminases / Q000378:metabolism
D012694:Serine; D002237:Carbohydrate Dehydrogenases; D050543:Phosphoglycerate Dehydrogenase; D012696:Glycine Hydroxymethyltransferase; D000637:Transaminases; C022638:serine-pyruvate aminotransferase; D012695:L-Serine Dehydratase