Homocysteine desulfhydrase

Kallio has partially purified the cysteine and homocysteine desulfhydrases from P. morganii and found that pyridoxal phosphate was active as cofactor. The possibility that threonine might be an intermediate in reaction 21 was ruled out by the finding that threonine was relatively inactive as a substrate. The role of pyridoxal phosphate as cofactor for animal desulfhydrases is suggested from the findings of Braunstein and Azarkh" that liver homogenates from pyridoxine-deficient animals had lower cysteine desulfhydrase activity than those from normal animals. Dietary supplementation with pyridoxine raised the activity to the normal level. 

The action of cysteine desulfhydrase is inhibited by hydrogen cyanide. Binkley and du Vigneaud (15) have observed that the production of hydrogen sulfide, which appears in the comrse of the reaction due either to homocysteine desulfhydrase or to cysteine desulfhydrase, is arrested in the presence of hydrogen cyanide, without however diminishing appreciably the yield of cysteine. This observation shows that the mechanism in question does not come into play in the experiments of Binkley and du Vigneaud, but the re.sults do not show that this mechanism plays no role in the animal. The theory of Toennies (121) assumes the existence of a direct transsulfuration between methionine and serine. This theory is based on the ability of methionine sulfur to form sulfonium derivatives... 

Other examples of PLP-requiring enzymes are the amino acid decarboxylases that lead to formation of amines, including several that are functional in nervous tissue (e.g., epinephrine, norepinephrine, serotonin, and y-aminobutyrate) cysteine desulfhydrase and serine hydroxymethyltransferase, which use PLP to effect the loss or transfer of amino acid side chains phosphorylase, which catalyzes phosphorolysis of the a-1,4-linkages of glycogen and cystathione beta-synthase in the transsulfiiration pathway of homocysteine. Additionally the biosynthesis of heme depends on the early... 

Cysteine Desulfhydrase. Cysteine undergoes a desulfuration that is believed to be analogous to the dehydration of serine. The enzyme cysteine desulfhydrase requires pyridoxal phosphate and forms pyruvate, H2S, and NH3. This enzyme has been found in animal liver and presumably occurs in microorganisms that release H2S from cysteine. Evidence has been obtained with H2S that indicates some reversibility of the reaction, but no thermodynamic data are available. A similar enzyme has been reported to form a-ketobutyrate, NH3, and H2S from homocysteine. ... 

Corroborative evidence has been obtained from experiments with isolated tissue preparations. The in vitro formation of cystine by liver slices (and a saline extract) was observed in nuxtures containing dl-homocysteine and DL-serine. Neither substance was effective when incubated alone. The L-forms of the two amino acids were implicated in the reaction, as D-homocysteine and o-serine did not substitute for the DL-forms and the isolated cystine had the L-configuration. The reaction proceeded best under anaerobic conditions and in the present of O.OOlAf CN , as the latter inhibits cysteine desulfhydrase activity. Methionine substituted very poorly for homocysteine in vitro. 

Binkley and Okeson purified the enzyme system that cleaves cystathionine and found that neither phosphate nor ATP was required for activity, thus correcting the previous report that ATP was required. In addition to splitting cystathionine, this enzyme preparation also produced H2S from cysteine. The authors suggest that their enzyme may be identical with cysteine desulfhydrase. Binkley also reported that he had been able to synthesize cystathionine enzymatically from homocysteine and serine by a fractionated liver preparation which had been freed from the cystathionine cleavage enzyme, serine dehydrase and homoserine deaminase. The activity of the enzyme synthesizing cystathionine was either inhibited or unaffected by ATP, DPN, AMP, and various metal ions. 

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