CHEMICAL PATHOLOGY OF HOMOCYSTEINE .3. CELLULAR FUNCTION AND AGING

The homocysteine thiolactonyl derivative, thioretinaco ozonide, is bel ieved to function as an electron acceptor in oxygen metabolism and as the binding site for adenosine triphosphate (ATP) synthesis by mitocho ndria, preventing damage by free radical oxidants in resting cells. Du ring cell division, methionine is converted to homocysteine thiolacton e, converting thioretinaco to thioco, increasing free radical oxidants , and oxidizing cellular glutathione and ascorbate. Homocysteic acid h as growth hormone activity and releases insulin-like growth factor in hypophysectomized rats, promoting oxidation of homocysteine thiolacton e to sulfated glycosaminoglycans of cartilage. The free base of homocy steine thiolactone produces keratinization, squamous metaplasia, dyspl asia, and carcinogenesis in normal mouse tissues. The efficiency of ho mocysteine thiolactone metabolism declines with aging, explaining decr eased formation of adenosyl methionine in aging and suggesting loss of thioretinaco ozonide from membranes of aging cells. The effects of ag ing on enzyme activity, connective tissues, lipid synthesis, auto-immu ne diseases, atherogenesis and carcinogenesis are related to these cha nges in homocysteine metabolism.