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.