Cystathionase synthetase

Trapping of the aminoacrylate intermediate in the reactions catalyzed by cystathionine-y-synthase and y-cystathionase produced the same diastereomer of KEDB which was different from the one formed with bacterial L-threonine dehydratase. Unfortunately, this experiment has apparently not been done with threonine synthetase. 

Figure 9.5. Methionine load test for vitamin Be status. Methionine synthetase, EC 2.1.1.13 (vitamin Bi2-dependent) 2.1.1.5 (betaine as methyl donor) cystathionine synthetase, EC 4.2.1.22 and cystathionase, EC 4.4.1.1. Relative molecular masses (Mr) methionine, 149.2 homocysteine, 135.2 cystathionine, 222.3 and cysteine, 121.2.

The metabolism of methionine, shown in Figure 9.5, includes two pyri-doxal phosphate-dependent steps cystathionine synthetase and cystathionase. Cystathionine synthetase is litde affected by vitamin Bg deficiency,... 

As discussed in Section 10.3.4.2, the metabolic fate of homocysteine arising from methionine is determined not only by the activity of cystathionine synthetase and cystathionase, hut also the rate at which it is remethylated to methionine (which is dependent on vitamin B12 and folate status) and the requirement for cysteine. 

There are several vitamin Bg-responsive inborn errors of metabolism that include (1) cases of infantile convulsions in which the apoenzyme for glutamate decarboxylase has a poor affinity for the coenzyme (2) a type of chronic anemia in which the number but not morphological abnormality of erythrocytes is improved by pyridoxine supplementation (3) xanthurenic aciduria in which affinity of the mutant kynureninase for PLP is decreased (4) primary cystathion-inuria caused by similarly defective cystathionase and (5) homocystinuria in which there is less of the normal cystathionine synthetase. In these cases increased levels (200 to lOOOmg/day) of administered vitamin Bg are required for life. Low vitamin Bg status (together with low vitamin B12 and folate status) in humans has been linked to hyperho-mocysteinemia and as an independent risk factor for cardiovascular disease. ... 

Cystathionase also has a low level of direct cysteine desulphydrase activity. Tryptophanase and tryptophan synthetase are other enzymes capable of carrying out the cysteine desulphydrase reaction. Such considerations have cast doubt on this biological significance of this reaction, although strong arguments have been presented for a true cysteine desulphydrase in SalmonellcP. 

Inhibitors of this type have been used in the irreversible inhibition of pyridoxal-linked aspartate aminotransferase, y-cystathionase, and tryptophan synthetase. These inhibitors are y-unsaturated amino acids. Aspartate aminotransferase is inhibited by molecules 1 and 2,... 

The metabolism of methionine, shown in Figure 11.22, includes two pyridoxal phosphate-dependent steps cystathionine synthetase and cystathionase. Cystathionase activity falls markedly in vitamin deficiency, and as a result there is an increase in the urinary excretion of homocysteine and cystathionine, both after a loading dose of methionine and under basal conditions. However, as discussed below, homocysteine metabolism is affected more by folate status than by vitamin status, and, like the tryptophan load test, the methionine load test is probably not reliable as an index of... 

The homocysteine moiety of methionine is converted to cystathionine by the enzyme, cystathionine synthetase. Cystathionine has been shown to be cleaved by cystathionase to cysteine and a-ketobutyric acid (63). Homoserine is also hydrolytically deaminated by the same enzyme to... 

Fig. 5. Regulation of the enzymes of methionine biosynthesis and related pathways. Enzymes catalyzing the synthesis of methionine and 5 -adenosylmethionine (SAM) from cysteine are (1) cystathionine y-synthase, (2) j9-cystathionase, (3) methionine synthase, and (4) SAM synthetase. Enzymes associated with the synthesis and metabolism of phospbohomoserine which are relevant to the regulation of methionine synthesis are (5) aspartate kinase, (6) homoserine kinase, and (7)...

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