Methylations are widespread in the biological kingdom. However, their chemical and biochemical roles have not been fully dissected. A hypothesis was put forward previously in which methylation is proposed to lead to hyperconjugation, whose electron donating feature weakens the chemical bonds and increases the bond lengths of C-N, therefore resulting in stronger secondary bonding between nitrogen atoms and cations or protonation of nitrogen atoms. Consequently ion homeostasis of the cells is compromised giving rise to certain diseases. Protonation of nitrogen atoms in 5-methyl cytosine enhances interaction with negatively charged phosphate groups and contributes to the formation of heterochromatin.
Overexpression of telomerase has been demonstrated to substantially extend the lifespan of mice. However, this treatment has a negative side, namely the increase of cancer risk. Most components of the telomerase holoenzyme complex possess high basic amino acid content, potentially attracting anions and enhancing the formation of mutagenic and carcinogenic HCl. Weak organic acids antagonize strong acids, and thus can raise cellular pH and modify the microenvironment. R-loops are hybrid DNA and RNA structures, and trigger DNA replication stress and genome instability. RNA has one additional hydroxyl oxygen atom on ribose compared with DNA, and single stranded DNA harbors bases free of hydrogen bonding. These two factors can enhance the buildup of protons via hydrogen bonding and the local formation of HCl. Strong acids generated can augment DNA mutagenesis, and enhance DNA excision, repair and formation of double stranded breaks. Neoplasm must be addressed before lifespan extension remedies via telomerase are ready for use.
Rheumatoid arthritis is a common human disorder which can be triggered by coldness and high humidity. However, the etiology of the illness is not well elucidated. Here we show that the molecular hallmarks of the risk factors may contribute to the causes and symptoms of the disease. Antagonism between insoluble and stiff calcium salts and acids is suggested from these features. Preventive strategies can be designed to cope with this disabling disease.
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