Chemical pathology of homocysteine. II. Carcinogenesis and homocysteine thiolactone metabolism.

Abstract

Abnormalities of methionine metabolism in malignancy include carcinogenicity of methionine deficiency, methionine auxotrophy of cultured malignant cells, deficient methylation of DNA, and aerobic glycolysis that is reversed by methionine. Cells from children with homocystinuria form an aggregated sulfated extracellular matrix and grow in a pattern similar to cultured malignant cells. Normal cells metabolize homocysteine thiolactone to sulfate, but malignant cells accumulate homocysteine thiolactone, which thiolates proteins and other cellular macromolecules. Thioretinamide, the amide of retinoic acid homocysteine thiolactone, and its cobalamin complex, thioretinaco, are antineoplastic and chemopreventive against carcinogenesis. Deficiency of these compounds in malignant cells is believed to increase conversion of methionine to homocysteine thiolactone and thioco, its cobalamin complex. These compounds are believed to participate in oxidative phosphorylation by formation of thioretinaco ozonide disulfonium complexes that are the active sites of adenosine triphosphate (ATP) binding in mitochondrial membranes. Hypothetical deficiency of thioretinaco may explain important metabolic abnormalities of malignant cells.

• Authors: K S McCully
• Journal: Annals of clinical and laboratory science (Ann Clin Lab Sci) 1994 Jan-Feb Vol. 24 Issue 1 Pg. 27-59 ISSN: 0091-7370 [Print] United States
• PMID: 8147567 (Publication Type: Journal Article, Review)

Chemical References

• Anticarcinogenic Agents
• Antineoplastic Agents
• Sulfates
• Homocysteine
• Methionine
• homocysteine thiolactone
• Oxygen

Topics

• Anticarcinogenic Agents
• Antineoplastic Agents
• Arteriosclerosis
• Homocysteine (analogs & derivatives, metabolism, pharmacology)
• Humans
• Methionine (metabolism)
• Neoplasms (chemically induced)
• Oxygen (metabolism)
• Sulfates (metabolism)