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 (Hcy), 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 Hcy (hyperhomocysteinemia) causes changes in redox thiol status. Protein-bound Hcy increases up to a maximum capacity of about 140 micromol/L, and there is a concurrent displacement of protein-bound cysteine. When the Hcy binding approaches saturation, free oxidized and reduced Hcy show a substantial increase. The resulting increase in reduced/total ratio for Hcy 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 Hcy 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 Hcy), 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 Hcy and cardiovascular disease.
Ueland
P M
PM
Division of Pharmacology, Department of Clinical Biology, University of Bergen, Norway.
Mansoor
M A
MA
Guttormsen
A B
AB
Müller
F
F
Aukrust
P
P
Refsum
H
H
Svardal
A M
AM
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000378:metabolism; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D010084:Oxidation-Reduction; D011485:Protein Binding; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D000975:Antioxidants; D013438:Sulfhydryl Compounds; D006710:Homocysteine