Current Enzyme Inhibition - Volume 3, Issue 4, 2007

Several xenobiotics cause oxidative DNA damage by reactive oxygen species (ROS) induction. The antioxidant defence system, including antioxidant enzymes, radical scavengers and chain breakers, limits cell injury induced by ROS. In particular the antioxidants such as reduced glutathione (GSH) and ascorbic acid (AA) and the antioxidant enzymes superoxide dismutase (SOD), catalase, glutathione peroxidase (G Read More

The activation and transduction of several signalling pathways are dependent on tyrosine phosphorylation. The non-transmembrane protein tyrosine phosphatase SHP-2 (Src homology 2 domain containing tyrosine phosphatase 2) has been shown to be involved in several signalling pathways initiated by different growth factors, cytokines, hormones and extracellular matrix receptors. SHP-2 directly interacts with sev Read More

Protein Tyrosine kinases (TKs) play important roles in regulating the most fundamental cell processes, such as the cell cycle, proliferation, differentiation, motility, and cell death or survival. In many tumor cells, key TKs may no longer be adequately controlled, and excessive phosphorylation sustains signal transduction pathways in an activated state. Imatinib mesylate is an oral multitargeted tyrosine kinase in Read More

Endothelial dysfunction due to reduced bioavailability of nitric oxide (NO) is an early step in the course of atherosclerotic cardiovascular disease. NO is synthesized from L-arginine via the action of NO synthase, which is known to be blocked by endogenous L-arginine analogues such as asymmetric dimethylarginine (ADMA). ADMA is a naturally occurring amino acid found in plasma and various types of tissues. Plasma lev Read More

Phospholipases A2 (PLA2) comprise a set of extracellular and intracellular enzymes that catalyze the hydrolysis of the sn-2 fatty acyl bond of phospholipids to yield fatty acids and lysophospholipids. The PLA2 reaction is the primary pathway through which arachidonic acid (AA) is released from phospholipids. PLA2s have an important role in cellular death that occurs via necrosis or apoptosis. Reactive oxygen species are kn Read More

Mitogen-activated protein kinases (MAPKs) are a family of serine-threonine kinases that respond to various extracellular signals and are involved in many cellular processes. The MAPK family consists of four major groups extracellular signal regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK), p38 and ERK5. Additional MAPKs (ERK3, ERK4, ERK7, ERK8) have been identified on the bas Read More

One of the most promising strategies for drug design and development is the identification of new molecules able to selectively inhibit those enzymes involved in pathological processes, without affecting other enzymes associated with physiological functions. Nevertheless, some enzymes can show a double-edge aspect of their own inhibition, which can lead to positive as well as negative consequences according to the pat Read More