Interrelations between plasma free and protein-bound homocysteine and cysteine in homocystinuria

To study the interrelations between plasma free and protein-bound homocysteine and cysteine, we measured the levels of these four variables in 167 samples from 17 patients with homocystinuria during different treatment regimens, 14 heterozygotes for cystathionine B-synthase deficiency, and 17 normal subjects. There was a strong positive correlation between free and protein-bound homocysteine, and between free and protein-bound cysteine over a wide range of values in varying clinical situations, but homocysteine and cysteine had differing binding characteristics. At low concentrations homocysteine bound more tightly than cysteine to plasma protein, while at high concentrations of the free amino acids more cysteine than homocysteine was bound to plasma protein. In patients with homocystinuria due to cystathionine B-synthase deficiency, levels of protein-bound homocysteine after an overnight fast were eight to 12 times higher than mean levels +/- SD in the normal subjects of 0.15 +/- 0.03 mumol/g of plasma protein, n = 17, and levels of protein-bound cysteine were lower than mean normal levels +/- SD of 2.30 +/- 0.23 mumol/g, n = 17. In the patients before treatment the proportions of both plasma thiols that were protein-bound were approximately half those in the normal subjects. For homocysteine the proportion was 35% in a representative patient and 78% in normal subjects and in heterozygotes, while for cysteine the corresponding proportions were 26% and 59%. In all blood samples the sum of the plasma free and protein-bound homocysteine and cysteine remained relatively constant (mean +/- SD = 270.6 +/- 68.6 mumol/L of plasma, n = 142).(ABSTRACT TRUNCATED AT 250 WORDS)