Human cystathionine gamma-lyase: developmental and in vitro expression of two isoforms

Cystathionine gamma-lyase (CGL) is the last enzyme of the trans-sulphuratio n pathway, which converts methionine into cysteine, To study the possible d ifferences in enzymic activity of the two human cystathionine gamma-lyase i soforms characterized earlier, these were separately expressed in human kid ney embryonic 293T cells. Furthermore, developmental changes in the express ion of the two mRNA forms as well as the enzymic activity in human liver we re studied, as it has been postulated that a change in the relative express ion of CGL isoforms causes the postnatal increase in CGL activity. Transfec tion with the longer isoform increased the CGL activity 1.5-fold, while the activity of the cells transfected with the shorter form did not differ fro m the basal activity. In human liver samples, CGL activity was only detecte d in adult tissue (68 +/- 9 nmol of cysteine/h per mg of protein), whereas activity in fetal, premature and full-term neonatal liver tissue was undete ctable. In contrast, strong mRNA expression of both mRNA isoforms was detec ted from the 19th gestational week onwards and the longer form of CGL appea red to be predominant. The expression of the two mRNA forms varied in paral lel. In conclusion, we have shown that only cells overexpressing the longer form of CGL have increased activity, and CGL appears to be regulated at th e post-transcriptional level during development.