Search

The glycine motif is widely prevalent in bioactive peptides. Thus, the direct and precise modification of glycine derivatives has attracted significant attention over the past few decades. Among various protocols for the modification of glycine derivatives, the visible-light-driven direct α-C(sp3)–H bond functionalization of glycine derivatives has emerged as a powerful tool to achieve this objective, owing to its merits in atom economy, selectivity, reaction simplicity, and sustainability. This review summarizes the recent advancements in visible-light-driven direct α-C(sp3)–H bond functionalization of glycine derivatives. The contents of this review are organized based on the photocatalysts employed and the various reaction modes in the functionalization process. The mechanism, the challenges encountered, and future trends are also discussed, enabling readers to understand the current developmental status in this field.

Brain excitation increases neuronal Na+ concentration by 2 major mechanisms: i) Na+influx caused by glutamatergic synaptic activity; and ii) action-potential-mediateddepolarization by Na+ influx followed by repolarizating K+ efflux, increasingextracellular K+ concentration. This review deals mainly with the latter and it concludesthat clearance of extracellular K+ is initially mainly effectuated by Na+,K+-ATPasemediatedK+ uptake into astrocytes, at K+ concentrations above ~10 mM aided by uptakeof Na+, K+ and 2 Cl- by the cotransporter NKCC1. Since operation of the astrocytic Na+,K+-ATPase requires K+-dependent glycogenolysis for stimulation of the intracellularATPase site, it ceases after normalization of extracellular K+ concentration. This allowsK+ release via the inward rectifying K+ channel Kir1.4, perhaps after trans-astrocyticconnexin- and/or pannexin-mediated K+ transfer, which would be a key candidate fordetermination by synchronization-based computational analysis and may have signalingeffects. Spatially dispersed K+ release would have little effect on extracellular K+concentration and allow K+ accumulation by the less powerful neuronal Na+,K+-ATPase,which is not stimulated by increases in extracellular K+. Since the Na+,K+-ATPaseexchanges 3 Na+ with 2 K+, it creates extracellular hypertonicity and cell shrinkage.Hypertonicity also stimulates NKCC1, which, aided by -adrenergic stimulation of theNa+,K+-ATPase, causes regulatory volume increase, furosemide-inhibited undershoot in[K+]e and perhaps facilitation of the termination of slow neuronal hyperpolarization(sAHP), with behavioral consequences. The ion transport processes involved minimizeionic disequilibria caused by the asymmetric Na+,K+-ATPase fluxes.

The involvement of glycogenolysis, occurring in astrocytes but not in neurons, in learning is undisputed (Duran et al., JCBFM, in press). According to one school of thought the role of astrocytes for learning is restricted to supply of substrate for neuronal oxidative metabolism. The present ‘perspective’ suggests a more comprehensive and complex role, made possible by lack of glycogen degradation, unless specifically induced by either i) activation of astrocytic receptors, perhaps especially beta-adrenergic, or ii) even small increases in extracellular K+ concentration above its normal resting level. It discusses i) the known importance of glycogenolysis for glutamate formation, requiring pyruvate carboxylation; ii) the established role of K+-stimulated glycogenolysis for K+ uptake in cultured astrocytes, which probably indicates that astrocytes are an integral part of cellular K+ homeostasis in the brain in vivo; and iii) the plausible role of transmitter-induced glycogenolysis, stimulating Na+,K+-ATPase/NKCC1 activity and thereby contributing both to the post-excitatory undershoot in extracellular K+ concentration and the memory-enhancing effect of transmitter-mediated reduction of slow neuronal afterhyperpolarization (sAHP).