Homocysteine-cysteine

Husek P, Matucha P, Vrankova A, Simek P. 2003. Simple plasma work-up for a fast chromatographic analysis of homocysteine, cysteine, methionine and aromatic amino acids. J Chromatogr B 789 311. 

The fraction of intracellular homocysteine that does not undergo transsulfuration or remethylation is secreted into the extracellular space and ultimately finds its way into the blood. One major source of blood homocysteine is the liver, but some homocysteine is secreted into the blood by endothelial cells, circulating blood cells, and other tissues. Only about 2% of homocysteine in blood remains in its reduced, thiol form. The remainder circulates as a variety of different oxidation adducts, which include the disulfide, homocystine, as well as homocysteine-cysteine mixed disulfide and several protein-bound disulfides.About 70% of total homocysteine in blood is bound to the protein albumin through a disulfide linkage.When blood homocysteine is measured in the clinical laboratory, a reducing agent is added to the sample... 

Substances related to MSG and purine 5 -ribonucleotides include peptides, amino acids (e.g. cysteine, homocysteine, cysteine S-sulfonic acid, aspartic acid, a-amino adipic acid, a-methyl glutamic acid, tricholomic acid, ibotenic acid), pyrrolidone carboxylic acid, 3-methyl thiopropyl amine, and others [2, 10], They are of less commercial interest than MSG, IMP, and GMP. Chemical structures of some of these substances are depicted in Fig. 3.53. Relative umami effects of some are shown in Tab. 3.49. Tricholomic acid and ibotenic acid have been found in the mushrooms Tricholoma muscarium and Amanita stroboliformis, respectively. 

Synergistic effects between MSG and sodium chloride have also been reported [8], For maximum palatability of a clear soup, more MSG must be added if only small amounts of salt are used, and vice versa. Optimum amounts of salt and MSG are 0.8 % and 0.4 %, respectively. Thaumatin, an intensely sweet tasting protein has been reported to have a similar synergistic effect to that of 5 -ribonucleotides on MSG, but at significantly lower dosages [8]. Other umami substances with synergistic effects on each other include various amino acids (e.g. L-cysteine, D,L-homocysteine, cysteine S-sulfonate), polypeptides, cycloalliin, and histamine [8]. 

In plasma, homocysteine is present as both free (< 1 %) and oxidized forms (>99%). The oxidized forms include protein (primarily albumin)-bound homocysteine mixed disulfide (80-90%), homocysteine-cysteine mixed disulfide (5-10%), and homocystine (5-10%). Several studies have shown the relationship between homocysteine and altered endothelial cell function leading to thrombosis. Thus, hyperhomocysteinemia appears to be an independent risk factor for occlusive vascular disease. Five to ten percent of the general population have mild hyperhomocysteinemia. 

Pastore A, Massoud R, Motti C, et al. FuUy automated assay for total homocysteine, cysteine, cysteinylglycine, glutathione, cysteamine and 2-mercaptopropionylglycine in plasma and urine. Clin Chem, 1998 44 825-832. 

H2S can be produced via the metabolism of sulfhydryl-bearing amino acids, specifically by several enzymes found in the methionine-homocysteine-cysteine pathway such as cystathionine 3 synthase (CBS) and cystathionine lyase (CGL) (Fig. 8.1) [6, 10, 11]. The sequence of CBS has been identified in genomes from bacteria to humans [12-14], and a gene similar to the sulfide quinone oxidoreductase gene has been identified in the genome of flies, worms, mice, rats, and humans [15], indicating that cellular H2S and its regulation may be widespread and essential. 

Cystathionine fisynthase (EC 4.2.1.22). Failure to form cystathionine from homocysteine and serine. Elevated homocysteine and methionine in serum. Urine contains homocystine and homocysteine-cysteine disulfide. Cystathionine virtually absent from brain, where it is normally present in significant quantities. Mental retardation. Lens detachment. Skeletal abnormalities (tall stature, arachnodactyly). Arterial and venous thrombosis. 

Homocysteine, cysteine- and homocysteine-S-bimane, and cysteine-S-bimane-glycine were extracted from plasma and serum samples were baseline resolved in lOmin using a Cg column (A = 390mn, ex >418nm, em) and a 5/95 100/0... 

Homocysteine, cysteine, and glutathione were isolated from serum and plasma, derivatized with monobromobimane, and separated on a 35°C C g column (A = 250 nm or 300 nm, ex 470 nm, em). An interesting 25-min gradient based on the volume delivered went firom 95/5 —>55/45 water (0.1% TFA)/acetonitrile [1276]. A linear range of 0.5-500 nmol/mL and a detection limit (fluorescence) of 5 pmol/mL were reported. 

Nolin, T. D., M. E. McMenamin, and J. Himmelfarb. 2007. Simultaneous determination of total homocysteine, cysteine, cysteinylglycine, and glutathione in human plasma by high-performance liquid chromatography Application to studies of oxidative stress. /. Chromatogr. B Anal. Technol. Biomed. and Life Sci. 852(1-2) 554-561. 

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... 

As in the case of homocysteine, cysteine sulfur may be split off the organic molecule in the form of hydrogen sulfide. This desulfuration is... 

---