Endogenous modulators in the regulation of ion transporting enzymes: structure, function, interactions, recent advancements and future perspectives ()
ABSTRACT
A prerequisite for life is the ability to uphold electro-chemical imbalance across biomembranes. Ion trans- porting enzymes, known as specific pumps, are re-sponsible for the transport of various ions across cell membranes to sustain the same. In all eukaryotes, the plasma membrane potential and secondary transport systems are maintained by the activity of P-type ion transporting enzymes, commonly known as ATPase membrane pumps. Malfunction of pumps leads to various cell disorders and subsequently diseases like cardiac problems, renal malfunctionings, diabetes, cataract, even cancer. Activities/functions of these pumps are regulated either by exogenous agents or by endogenous substances like proteins, peptides, hormones, etc., which are collectively known as mo- dulators. Some of these endogenous modulators may be useful for developing drugs depending on the na-ture of regulation. For more than last two decades, researchers across the globe are exploring the me- chanism of action of different endogenous modulators on these ion transporting enzymes with the aim of developing target-specific drugs. In this review, we have discussed recent advances in our understanding of ATPase pumps, e.g., Ca2+-, Na+, K+-, Ca2+, Mg2+-, H+, K+-ATPases, with the emphasis on their functional regulation by a number of endogenous modulators, and the implications of development of some of these modulators as potential drugs.