Homocystine-cysteine mixed disulphide

Reaction 4 is catalysed by cystathionine synthase (EC 4.2.1.13), an enzyme widely distributed in the tissues. In homocystinuria, cystathionine synthase is virtually completely absent or inactive in all tissues examined liver, brain and fibroblasts grown in tissue culture [33]. In some cases 1 to 2% of the normal enzymic activity can be demonstrated, in others no enzymic activity has been found [34]. As a result of the metabolic block, homocysteine accumulates and is partly converted to homocystine, partly to homocysteine-cysteine mixed disulphide and partly S-methylated to methionine by reactions 6 and 7 with, respectively, N -methyltetrahydrofolic acid and betaine as methyl donors. In infancy methionine and homocysteine are present in high concentrations in the plasma while homocystine and homocysteine-cysteine mixed disulphide are excreted in the urine later the concentration of methionine in the plasma drops. Cystathionine is normally present in highest concentration in the cells of the brain, though traces are found elsewhere and in the urine in homocystinuria no cystathionine can usually be demonstrated in the brain or urine [35]. The body s cysteine and cystine are also largely biosynthesized from methionine, though some is obtained from cysteine and cystine in dietary proteins in homocystinuria, cysteine/cystine becomes an essential amino acid. 

Cystathionine synthase has pyridoxal phosphate as cofactor a radically different form of treatment was introduced in 1967 giving pyridoxine at a dosage level of 50 to 200 mg per day [40]. The concentrations of methionine and homocysteine in the blood, and of homocystine and homocysteine-cysteine mixed disulphide in the urine, fell sharply on such treatment in... 

Hey is a sulphydryl amino acid of molecular weight 135.2. It oxides readily to its disulphide form homocystine, and can be converted to the thiolactone form in acid solution. In normal plasma, Hey exists in various forms the sulphydryl form (approximately 1%), bound to the cysteine residues of proteins (approximately 70%), and bound to free cysteine as cysteine-Hcy mixed disulphide (approximately 30%). When levels are elevated, the disulphide form homocystine is formed. All of these forms can be converted to Hey by chemical reduction and then measured as tHcy. 

Thiols exist in biological systems in various oxidised and reduced forms. Very little Hey in the free sulphydryl form is found in plasma and it exists mainly as cysteine-Hcy mixed disulphide, bound to cysteine residues of plasma proteins, or as its disulphide homocystine, but the latter only when levels are high. Routinely measured tHcy constitutes all of these forms together and is produced by chemical reduction. 

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