Considerable research has been conducted into the activity of CSE, the enzyme responsible for converting cystathionine to cysteine via the transsulphuration pathway in the preterm neonate. CSE activity is gestational- and postnatal-age dependent, with significantly higher levels of hepatic activity in full term than preterm newborns. This hepatic activity is known to increase during fetal-to-neonatal transition, such that the newborn exhibits significantly higher activity compared to the fetus, with significantly increased levels of both mRNA and protein. The results of the present study, which show a high total body turnover of H2S in the initial extrauterine period, are at odds with earlier reports of CSE activity being lower in preterm than term newborns. This may be a result of tissue specific Pulchinenoside-B regulation: previous studies have looked only at hepatic activity, whereas our results reflect total body H2S turnover. These earlier studies looked at the conversion of cystathionine to cysteine as the end point of the CSE mediated pathway, however, CSE is also responsible for the further downstream metabolism of cysteine which results in H2S production, and this second role, which was not previously studied, may result in an accelerated breakdown of cysteine in the preterm neonate, contributing to high levels of H2S during circulatory transition. Additionally, high H2S production could also occur in the absence of high endogenous cysteine as CSE can also use homocysteine and cystathionine as substrates to produce H2S. It is also possible that the CSE arm of the H2S production pathway is not the predominant player in H2S production during the perinatal period. CBS and MPST are also known to catalyze the production of H2S. The concept of H2S production enzymes following a tissue-specific expression profile is currently being challenged. Until recently, it was believed that the major source of H2S in the vasculature was CSE. More recently it has been shown that CBS, the enzyme originally thought to be responsible for H2S production predominantly in the brain and nervous tissue, is also Polyphyllin-VII expressed in the vasculature, and a third, more recently discovered pathway for synthesizing H2S via MPST has also been identified in rodent vasculature.