Ks. Mccully, CHEMICAL PATHOLOGY OF HOMOCYSTEINE .2. CARCINOGENESIS AND HOMOCYSTEINE THIOLACTONE METABOLISM, Annals of clinical and laboratory science, 24(1), 1994, pp. 27-59
Abnormalities of methionine metabolism in malignancy include carcinoge
nicity of methionine deficiency, methionine auxotrophy of cultured mal
ignant cells, deficient methylation of DNA, and aerobic glycolysis tha
t is reversed by methionine. Cells from children with homocystinuria f
orm an aggregated sulfated extracellular matrix and grow in a pattern
similar to cultured malignant cells. Normal cells metabolize homocyste
ine thiolactone to sulfate, but malignant cells accumulate homocystein
e thiolactone, which thiolates proteins and other cellular macromolecu
les. Thioretinamide, the amide of retinoic acid homocysteine thiolacto
ne, and its cobalamin complex, thioretinaco, are antineoplastic and ch
emopreventive against carcinogenesis. Deficiency of these compounds in
malignant cells is believed to increase conversion of methionine to h
omocysteine thiolactone and thioco, its cobalamin complex. These compo
unds are believed to participate in oxidative phosphorylation by forma
tion of thioretinaco ozonide disulfonium complexes that are the active
sites of adenosine triphosphate (ATP) binding in mitochondrial membra
nes. Hypothetical deficiency of thioretinaco may explain important met
abolic abnormalities of malignant cells.