Secondary Chemical Bonding between Insoluble Calcium Oxalate and Carbonyl Oxygen Atoms of GLY and VAL Residues Triggers the Formation of Aβ Aggregates and Their Deposition in the Brain

Abstract

Despite intense efforts, the cause of Alzheimer’s disease is still not fully understood. A chemical and biochemical perspective could shed light on this disorder. Secondary chemical bonding between calcium and carbonyl oxygen atoms of glycine and valine might give rise to aggregates in the brain, which may later result in cell senescence. The decrease of solubility caused by amino acid substitutions in specific risk factors compounds insolubility issue and likely triggers early-onset Alzheimer’s disease. Occasionally the enhancement of hydrogen bonding by amino acid replacements can reinforce the aggregates. Therefore, secondary chemical bonding to cations can generate cellular stresses in patients with Alzheimer’s disease in addition to other chemical and biochemical interactions such as salt bridge. The distinction between early-onset and late-onset Alzheimer’s disease risk factors may lie in the total capacity of a protein or local potency of a protein fragment to bind calcium or/and oxalate as calcium oxalate is highly insoluble and stressful.

Coexistence of hydrogen bonding and Secondary chemical bonding to calcium in rheumatoid arthritis

“…Valine and glycine have long carbonyl bond lengths and weakened carbonyl bonds, consequently enabling potent secondary chemical bonding to divalent cations in carbonyl oxygen atoms. [10][11][12] It is clear that both the content of total valine plus glycine and basic amino acids exceeded 10%, and can reach 20% to 30% in some cases, which result in the production of insoluble, stiff and stressful calcium salts. [10][11][12][13][14] The generation of insoluble calcium salts can lead to joint stiffness.…”

“…[10][11][12] It is clear that both the content of total valine plus glycine and basic amino acids exceeded 10%, and can reach 20% to 30% in some cases, which result in the production of insoluble, stiff and stressful calcium salts. [10][11][12][13][14] The generation of insoluble calcium salts can lead to joint stiffness. The presence of rich valine plus glycine in the risk factors may account for the lifespan shortening phenomena in RA sufferers.…”

The requisite for acid generation to solubilize insoluble salts may account for surge of glucose levels in some diabetes patients

“…The proteins of SARS-CoV-2 virus are high in valine plus glycine which have long carbonyl bond lengths and are projected to possess potent secondary chemical bonding and bind calcium effectively [3][4][5][6]. Oxalate can be generated from Krebs cycle, gluconeogenesis and other pathways [3], particular in winter when energy metabolism is robust.…”

The need for accessibility to chloride to solubilize insoluble salts may underlie some cases of hypertension

“…With long carbonyl bond lengths, glycine has been shown to chelate zinc and other divalent cations previously [7]. Valine is also projected to possess secondary chemical bonding [8]. Oxalate is produced from energy metabolism which is robust at low ambient temperature such as winter temperature [2,9].…”