REDUCED, OXIDIZED AND PROTEIN-BOUND FORMS OF HOMOCYSTEINE AND OTHER AMINOTHIOLS IN PLASMA COMPRISE THE REDOX THIOL STATUS - A POSSIBLE ELEMENT OF THE EXTRACELLULAR ANTIOXIDANT DEFENSE SYSTEM

Reduced, oxidized and protein-bound forms of homocysteine (Hey), cyste ine and cysteinylglycine in plasma interact via redox and disulphide e xchange reactions, and these aminothiol species comprise a dynamic sys tem referred to as redox thiol status. Notably, in plasma reduced cyst eine is the most abundant low molecular weight sulfhydryl compound. El evation of plasma Hey (hyperhomocysteinemia) causes changes in redox t hiol status. protein-bound Hey increases up to a maximum capacity of a bout 140 mu mol/L, and there is a concurrent displacement of protein-b ound cysteine. When the Hey binding approaches saturation, free oxidiz ed and reduced Hey show a substantial increase. The resulting increase in reduced/total ratio for Hey causes a parallel change in this ratio for the other aminothiols. These dynamics were observed during both c hronic hyperhomocysteinemia (due to cobalamin deficiency or homocystin uria) and acute hyperhomocysteinemia (induced by methionine or Hey loa ding). In addition, changes in redox thiol status have been observed i n patients with vascular disease (decreased reduced/total ratio for cy steine), renal failure (low reduced/total ratio for aminothiols) or HI V infection (high level of reduced Hey), which suggest primary imbalan ce between prooxidant and antioxidant processes in these patients. In conclusion, redox thiol status is a dynamic system which is probably l inked to the extracellular antioxidant defence system. This must be ta ken into account when designing future experimental or epidemiological studies on Hey and cardiovascular disease.