PROTEIN-BOUND HOMOCYST(E)INE IN NORMAL SUBJECTS AND IN PATIENTS WITH HOMOCYSTINURIA

A method was developed to quantitate protein-bound homocysteine using 2-mercaptoethanol. Protein-bound homocyst(e)ine was discovered in the plasma from normal individuals, ranging from 0.5-2.2 nmole/ml. In two obligatory heterozygotes for classical homocystinuria, plasma protein-bound homocyt(e)ine was 3.5 and 4.8 nmole/ml, respectively. Untreated homozygotes showed approximately a 40-fold increase of plasma protein-bound homocysteine. Furthermore, using conventional methods, no free homocystine was detectable in the supernatant of plasma precipitate from two classical homocystinuric patients treated with pyridoxine, but plasma protein-bound homocyst(e)ine showed a 10-fold increase. Protein-bound homocyst(e)ine was also demonstrated in the liver, kidney, and brain tissues from a patient with methyl- enetetrahydrofolate reductase deficiency. Speculation: The results in this study suggest that determination of protein- bound homocyst(e)ine using 2-mercaptoethanol may provide a more reliable assessment of treatment in patients with homocystinuria and a potentially useful tool for the definition of the carrier state. Demonstration of protein-bound homocyst(e)ine in various tissues of homocystinuric patients suggests the possibility that this compound may be directly associated with the development of some of the pathologic changes in the tissues. © 1979 International Pediatric Research Foundation, Inc.