Pathophysiological role substrates

Selective kinase inhibitors are invaluable tools to dissect the physiologic and pathophysiologic roles of protein kinases, to identify new substrates, to identify model systems that allow evaluation of potential clinical use, and importantly, to develop new therapeutic agents. 

Mammalian poly (ADP-ribose) polymerase-1 (PARP-1) is a nuclear chromatin associated protein and belongs to a lai e family of enzymes that can synthesize large branched polymers of ADP-ribose units by using -nicotinamide adenine dinucleotide (NAD ) as substrate. A pathophysiological role for PARP-1 has been demonstrated in a number of diseases and animal models using PARP-1 knockout mice. 

In recent years, the importance of enzyme levels in body fluids for clinical diagnosis has been recognized. It has been established that activities of secreted enzymes and cellular enzymes in serum are a sensitive indication of the pathophysiological condition of the body. Specific and sensitive substrates play a prominent role for this purpose. Fluorogenic substrates, e.g., enable sensitive micro-analyses. 

This chapter will focus on the families of enzymes that oxidize PUFA, their cellular location, function and substrate specificity, and introduce the role they and their enzymatic products play in cellular health and pathophysiological conditions. 

---