Exceptional Allosteric Regulation of Methylation Enzymes

The objective of this study is to bring up exceptional importance of methylation enzymes (MEs) in the regulation of cell replication of differentiation to subject these enzymes to double allosteric regulations and to pay attention to destabilization of abnormal MEs as a critical allosteric regulation of cancer therapy. MEs are a ternary enzyme complex consisting of methionine adenosyltransferase (MAT)-methyltransferase (MT)-S-adenosylhomocysteine hydrolase (SAHH), which play an essential role to regulate cell replication and differentiation in response to allosteric regulation. MEs are subject to double allosteric regulations, one at the individual enzymes and another at the enzyme complex. On the individual enzymes, SAHH is the receptor of steroid hormones or related allosteric regulators which dictates the optimum of growth and differentiation. Allosteric regulators play an essential role to maintain biological optimum to avoid hazardous extreme often to result in the display of clinical symptoms. On the enzyme complex, the association with telomerase changes kinetic properties of MAT and SAHH to alter the regulation in favor of growth. Primitive stem cells such as embryonic stem cells (ESCs) and progenitor stem cells (PSCs) express telomerase. Cells with abnormal MEs have a great advantage on growth. The nature creates chemo-surveillance as an allosteric regulation to destabilize abnormal MEs to keep cells with abnormal MEs under control.

Wound healing requires the proliferation and the terminal differentiation of PSCs. The functionality of chemo-surveillance dictates the success of wound healing. If the functionality of chemo-surveillance has been damaged due to pathological conditions, then the terminal differentiation of PSCs will be affected to result in very serious illnesses such as tissue fibrosis, dementia and organ failure. Wound unhealing can also force PSCs to evolve into cancer stem cells (CSCs) through silencing of TET-1 enzyme to escape contact inhibition that limits the proliferation of PSCs. The proliferation of CSCs cannot heal the wound because of the collapse of chemo-surveillance, which are then forced to progress to fast growing cancer cells (CCs) by the activation of oncogenes and/or the inactivation of suppressor genes. Obviously, the best approach of therapies of illnesses due to wound unhealing is to restore the functionality of chemo-surveillance. CDA formulations are, therefore, the best drugs for cancer therapy to fulfill cancer moonshot and to win the war on cancer.