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), cysteine and cysteinylglycine in plasma interact via redox and disulphide exchange reactions, and these aminothiol species comprise a dynamic system referred to as redox thiol status. Notably, in plasma reduced cysteine is the most abundant low molecular weight sulfhydryl compound. Elevation of plasma Hey (hyperhomocysteinemia) causes changes in redox thiol status. protein-bound Hey increases up to a maximum capacity of about 140 mu mol/L, and there is a concurrent displacement of protein-bound cysteine. When the Hey binding approaches saturation, free oxidized 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 chronic hyperhomocysteinemia (due to cobalamin deficiency or homocystinuria) and acute hyperhomocysteinemia (induced by methionine or Hey loading). In addition, changes in redox thiol status have been observed in patients with vascular disease (decreased reduced/total ratio for cysteine), renal failure (low reduced/total ratio for aminothiols) or HIV infection (high level of reduced Hey), which suggest primary imbalance between prooxidant and antioxidant processes in these patients. In conclusion, redox thiol status is a dynamic system which is probably linked to the extracellular antioxidant defence system. This must be taken into account when designing future experimental or epidemiological studies on Hey and cardiovascular disease.