Glutathione synthase deficiency

When present in excess methionine is toxic and must be removed. Transamination to the corresponding 2-oxoacid (Fig. 24-16, step c) occurs in both animals and plants. Oxidative decarboxylation of this oxoacid initiates a major catabolic pathway,305 which probably involves (3 oxidation of the resulting acyl-CoA. In bacteria another catabolic reaction of methionine is y-elimination of methanethiol and deamination to 2-oxobutyrate (reaction d, Fig. 24-16 Fig. 14-7).306 Conversion to homocysteine, via the transmethylation pathway, is also a major catabolic route which is especially important because of the toxicity of excess homocysteine. A hereditary deficiency of cystathionine (3-synthase is associated with greatly elevated homocysteine concentrations in blood and urine and often disastrous early cardiovascular disease.299,307 309b About 5-7% of the general population has an increased level of homocysteine and is also at increased risk of artery disease. An adequate intake of vitamin B6 and especially of folic acid, which is needed for recycling of homocysteine to methionine, is helpful. However, if methionine is in excess it must be removed via the previously discussed transsulfuration pathway (Fig. 24-16, steps h and z ).310 The products are cysteine and 2-oxobutyrate. The latter can be oxidatively decarboxylated to propionyl-CoA and further metabolized, or it can be converted into leucine (Fig. 24-17) and cysteine may be converted to glutathione.2993... 

Transsulfuration is facilitated by the action of two vitamin Be-dependent enzymes, cystalhionine-p-synthase (CBS), the enzyme deficient in homocystinuria, and cystathionine-Y-lyase (CTH). CBS catalyzes the condensation of homocysteine and serine to cystathionine, and CTH subsequently catalyzes the hydrolysis of cystathionine to cysteine and a-ketobutyrale. Cysteine is important in protein synthesis and taurine synthesis and is a precursor to glutathione, a strong antioxidant and essential compound in detoxification of many xenobiotics [8,10,11]. 

It is well known that, Se is a contradictory nutrient, where it has been called the essential poison—too much of it in the diet can be toxic too little can result in chronic, and sometimes fatal, deficiency (Reilly 2006). Organisms that require Se for normal cellular function contain essential selenoproteins, such as glutathione peroxidase, formate dehydrogenase, and selenophosphate synthase. Interestingly,... 

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