Pyridoxal phosphate transsulfuration

The transsulfuration pathway involves conversion of homocysteine to cysteine by the sequential action of two pyridoxal phosphate (vitamin B6)-dependent enzymes, cystathionine- 5-synthase (CBS) and cystathionine y-lyase (Fig. 21-2). Transsulfuration of homocysteine occurs predominantly in the liver, kidney, and gastrointestinal tract. Deficiency of CBS, first described by Carson and Neill in 1962, is inherited in an autosomal recessive pattern. It causes homocystinuria accompanied by severe elevations in blood homocysteine (>100 (iM) and methionine (>60 (iM). Homocystinuria due to deficiency of CBS occurs at a frequency of about 1 in 300,000 worldwide but is more common in some populations such as Ireland, where the frequency is 1 in 65,000. Clinical features include blood clots, heart disease, skeletal deformities, mental retardation, abnormalities of the ocular lens, and fatty infiltration of the fiver. Several different genetic defects in the CBS gene have been found to account for loss of CBS activity. 

As noted above, cystathionine formation is the other major fate of methionine. The condensation of homocysteine with serine is catalyzed by the vitamin requiring enzyme cystathionine P-synthase. In the last step of the transsulfuration sequence, cystathionine undergoes cleavage to cysteine and a-ketobutyrate in yet another enzyme reaction that requires pyridoxal phosphate. 

Synthesis of Sulfur Amino Acids. Of the many oxidation states of sulfur, only sulfite has been shown to be utilized by cell-free systems in the net synthesis of compounds with carbon-sulfur bonds, although mutant studies have indicated that more reduced forms can be incorporated. The formation of cysteinesulfinic acid from sulfite has been demonstrated in extracts of acetone-dried rabbit kidney it is possible that this reaction participates in the principal mechanism of sulfur incorporation. In many organisms that require preformed sulfur amino acids, cysteine may be formed from methionine. Only the sulfur of methionine is transferred to cysteine the carbon skeleton of cysteine is derived exclusively from serine. Transsulfuration appears to require the formation of homocysteine from methionine. Homocysteine and serine condense to form a thioether, cystathionine (V). Pyridoxal phosphate has been... 

Pyridoxal phosphate has definitely been shown to be the coenzyme in the transsulfuration reaction.This is highly interesting in view of the many enzyme reactions in which it is now known to participate. Vitamin... 

Homocysteine is metabolized in the liver, kidney, small intestine and pancreas also by the transsulfuration pathway [1,3,89]. It is condensed with serine to form cystathione in an irreversible reaction catalyzed by a vitamin B6-dependent enzyme, cystathionine-synthase. Cystathione is hydrolyzed to cysteine that can be incorporated into glutathione or further metabolized to sulfate and taurine [1,3,89]. The transsulfuration pathway enzymes are pyridoxal-5-phosphate dependent [3,91]. This co-enzyme is the active form of pyridoxine. So, either folates, cobalamin, and pyridoxine are essential to keep normal homocysteine metabolism. The former two are coenzymes for the methylation pathway, the last one is coenzyme for the transsulfuration pathway [ 1,3,89,91 ]. 

Kery, V., Bukovska, G., and Kraus, J.P (1994) Transsulfuration depends on heme in addition to pyridoxal 5 -phosphate. Cystathionine beta-synthase is a heme protein. J. Biol. Chem. 269, 25283-25288. 

Les memes experiences revdierent une depression marquee, chez les rats en avitapiinose Bt, de I incorparation du soufre isotoinque, aux frais des deux enan-tiomorphes de la metbicmine, dans la C rstine des proteines (20). Ce resultat etait h, prevoir, etant donne que le phosphate de pyridoxal fait partie des deux enzymes operant la transsulfuration (17,21). 

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