Background: Ribose-1,5-bisphosphate isomerase (R15Pi) converts ribose 1,5-bisphosphate into ribulose 1,5-bisphosphate in a novel AMP metabolic pathway. Results: Crystal structures of reaction-ready and -completed states are determined.
Conclusion:R15Pi undergoes an open-closed conformational change upon substrate binding, and the reaction proceeds via a cis-phosphoenolate intermediate.
Significance:The mechanism of ribose isomerization revealed in this study could be applied on other 1-phosphorylated ribose isomerases.
.
This study aimed to characterize the safety and effectiveness of GH
treatments, in usual clinical practice, in children with short stature born small for
gestational age (SGA). This was a multicenter, open-label, non-interventional study
(
NCT01110928
) conducted at 150 sites in Japan (2009–2018). The
primary objective was to assess the type and frequency of serious adverse drug reactions
(SADRs) associated with long-term GH use. Overall, 452 naïve and 46 non-naïve (previously
treated) children were enrolled. GH treatment was well‑tolerated, with SADRs occurring in
1.3% (6/452) and 0% (0/46) of naïve and non-naïve children, respectively. No new safety
concerns or notable changes in glucose metabolism were identified during long-term
treatment. Altogether, 57 children (32 naïve and 25 non-naïve) reached near adult height
(NAH). In naïve and non-naïve children, mean ± standard deviation (SD) height standard
deviation score (SDS) at NAH were –2.03 ± 0.77 and –1.53 ± 0.81, respectively,
representing a change of +0.85 ± 0.72 and +1.24 ± 0.66 from baseline height SDS,
respectively. Mean treatment duration to NAH was 4.29 (naïve) and 7.26 (non-naïve) yr.
Thus, long-term GH treatment for short stature in children born SGA was confirmed to have
a good safety profile and was effective for improving adult height.
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