L-cystathionine

L-cystathionine L-homoserine + L-cysteine cystathionine-y- synthase Streptomyces phaeochromogenes ... 

Cystamine dihydrochloride, S,5-(L,L)-Cystathionine, Cysteamine, Cysteamine hydrochloride, ( )-Cysteic acid, S-Cysteic acid (H2O), L-Cysteine hydrochloride (H2O), ( )-Cysteine hydrochloride and L-Cystine, Cytidine, see entries in Chapter 6. 

In some organisms sulfur incorporation involves homocysteine as an intermediate. In such cases cysteine formation occurs by a transsulfuration reaction, with the intermediate formation of L,L-cystathionine (fig. 21.86). Cystathionine is formed in a simple condensation reaction from serine and homocysteine by cystathionine-jS synthase. 

The vitamin B6-dependent enzyme CBS catalyzes the first step, in which homocysteine reacts with serine to form L-cystathionine. In the second step, L-cystathionine is converted to L-cysteine, a-ketobutyrate, and ammonia by the vitamin B6-dependent enzyme cystathionase (7). 

Radioactive L-cystathionine (10) (765 mg.) containing 6.85 x 106 counts per minute of S35 was fed to the human cystinuric patient who had served previously as the subject in an experiment demonstrating the formation of cystine from sulfur-labeled methionine (11). The same precautions were followed with regard to human experimentation involving radioactive material as in the latter experiment. After the feeding of the cystathionine, 24-hour urine specimens were collected for 3 days and sulfur distributions were determined by the titrimetric method of Fiske (6). Cystine determinations were carried out by the procedure of Sullivan, Hess, and Howard (12). 

Our findings in this study are in harmony with the concept that L-cystathionine is an intermediate in the formation of cystine from methionine in man. Direct evidence for the existence of cystathionine in man was provided by the demonstration by Tallan, Moore, and Stein (13) of the occurrence of L-cystathionine in extracts of human brain. Moreover, cases of human cystathioninuria have been reported by Harris, Penrose, and Thomas (9) and by Frimpter, Haymovitz, and Horwith (8). The latter authors have also stated that an increased renal clearance of cystathionine is not observed in cystinuria. It is of considerable interest, however, that the mixed disulfide of L-cysteine and L-homo-... 

S,S-(L,L)-Cystathionine (S-2-amino-2-carboxyethyl-L-homocysteine, L-2-amino-4[(2-amino-2-carboxyethyI)thio]butyric acid) [56-88-2] M 222.3, m >300°, dec at 312° with darkening at 270°, [ajp +23.9° (c 1, M HCI). Could be converted to the HCl salt by dissolving in 20% HCl and carefully basifying with aqueous NH3 until separation is complete. Filter off and dry in a vacuum. It forms prisms from H2O. The dibenzoyl derivative has m 229° (from EtOH). [IR Greenstein and Winitz Chemistry of the Amino Acids (J Wiley) Vol 3 2690 7967 and Tallan et al. J Biol Chem 230 707 1958 Synthesis du Vigneaud et al. J Biol Chem 143 59 1942 Anslow et al. J Biol Chem 166 39 7946.]... 

TaUanHH, Moore S, Stein WH. (1958) L-cystathionine in human brain. J Biol Chem 230 707-716. 

Cystathionine y-synthase (CGS) is a rather unique PLP-enzyme that catalyzes a transsulfuration reaction important in microbial methionine biosynthesis. It is the only known enzyme whose function is the catalysis of a PLP-dependent replacement reaction at the y-carbon of the amino acid substrate the succinyl moiety of O-succinyl-L-homoserine is replaced by i-Cys to give the thioether linkage of L,/.-cystathionine (scheme II). In the absence of L-Cys, the enzyme catalyzes a net y-elimination reaction from OSHS (scheme II). Because both reactions require the elimination of succinate, the catalytic pathways must diverge from a common reaction intermediate. It was originally hypothesized that a vinylglycine quinonoidal intermediate (structure 11)... 

In /3-replacement reactions, the /3-substituent of an amino acid substrate is replaced by a new /3-substituent. For the three enzymes (TRPS, OASS, and cystathionine /3-synthase (CBS)) whose mechanisms are discussed in this section, the catalytic reaction is composed of two distinct half-reactions. The /3-elimination is followed by a /3-addition where nucleophilic agents, indole, sulfide, and homocysteine, respectively, react with the ci-aminoacrylate Schiff base to form the final product, L-tryptophan, L-cysteine, and L-cystathionine, respectively. 

Human CGL displays an interesting substrate specificity with clear preference of C-S over S-S bond breakage L-cysteine and L-cystine are converted orders of magnitudes more slowly than the natural substrate L-cystathionine. The yeast enzyme attacks the C-/3-S bond of L-cystine or L-cysteine, whereas the streptomyces enzyme is quite active toward L-cystine. A CGL enzyme from Lactococcus lactis was reported to consist of at least six identical subunits and have a broad substrate specificity and relatively low specific activity toward L-cystathionine compared to bacterial CGL. In humans, L-cystathionine is split almost exclusively in... 

Only two enzymes (threonine synthase (TS) and CGS) are known to catalyze the 7-replacement reaction, which is composed of two distinct half-reactions. The mechanism involves the elimination of the 7-leaving group, followed by a Michael addition, where water or cysteine reacts with the /3,7-unsaturated ketimine to form the final product, L-threonine and L-cystathionine, respectively. In the case of TS, the addition is on the /3-carbon. 

Since even a slightly elevated L-cysteine concentration is inhibitory or possibly toxic for the cells E. coli possesses another mechanism for detoxification of this compound in addition to excretion degradation of L-cysteine. Five enzymes with L-cysteine desulfhydrase activity have been identified so far in this organism L-tryptophanase (TnaA), L-cystathionine p-lyase (MetC),... 

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