Cystathionine methionine catabolism

The subsequent cleavage of cystathionine to yield cysteine, a-ketobutyrate and NH4+ is catalyzed by y-cystathionase, a pyridoxal-phosphate-containing enzyme. This transsulfura-tion pathway is one of the routes used for methionine catabolism. 

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... 

A hypothesis has been proposed to explain all known causes of hyperho-mocysteinemia by a single, biochemical principle (Selhub and Miller 1992). The hypothesis emphasizes the existence of coordinate regulation by AdoMet of the partitioning of homocysteine between methionine synthesis and catabolism through cystathionine synthesis Elevated homocysteine levels in blood can be caused by a number of factors, including folate and B vitamin (B12, Bg) deficiency and pre-existing diseases such as atherosclerotic disease, diabetes and by various drugs. 

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