Search

Monoterpenoid indole alkaloid (MIA) biosynthesis in Catharanthus roseus is a paragon of the spatiotemporal complexity achievable by plant specialized metabolism. Spanning a range of tissues, four cell types, and five cellular organelles, MIA metabolism is intricately regulated and organized. This high degree of metabolic differentiation requires inter-cellular and organellar transport, which remains understudied. Here, we have characterized a vacuolar importer of secologanin belonging to the multidrug and toxic compound extrusion (MATE) family, named CrMATE1. Phylogenetic analyses of MATEs suggested a role in alkaloid transport for CrMATE1, and in planta silencing in two varieties of C. roseus resulted in a shift in the secoiridoid and MIA profiles. Subcellular localization of CrMATE1 confirmed tonoplast localization. Biochemical characterization was conducted using the Xenopus laevis oocyte expression system to determine substrate range, directionality, and rate. We can confirm that CrMATE1 is a vacuolar importer of secologanin, translocating 1 mM of substrate within 25 min. The transporter displayed strict directionality and specificity for secologanin and did not accept other secoiridoid substrates. The unique substrate-specific activity of CrMATE1 showcases the utility of transporters as gatekeepers of pathway flux, mediating the balance between a defense arsenal and cellular homeostasis.Characterization of CrMATE1 as a vacuolar importer of secologanin in Catharanthus roseus; the transport of secologanin is required for the first committed step of monoterpenoid indole alkaloid biosynthesis, ultimately leading to the anticancer drug vinblastine. [ABSTRACT FROM AUTHOR]

Objective: The objective of this review is to investigate the use of the subcutaneous route of administration of analgesics, common practice within palliative medicine. Design: Systematic review using consensus approach, direct comparison of subcutaneous route with intravenous and intramuscular routes. Results: The limited available evidence demonstrates non-inferiority of the subcutaneous route in both cancer patients and those post-surgery. Pain management is comparable to other routes. Route-related side effects are rare and systemic side effects are comparable. Conclusion: Pain management is a critical role of palliative medicine. The subcutaneous route of administration offers a viable option for the delivery of parenteral analgesia within all settings, including the community. This review supports current practice, demonstrating equivalence with more invasive routes of administration. [ABSTRACT FROM AUTHOR]