Bioenergetics of life, disease and death phenomena

Abstract

In this article, some new aspects of unified cell bioenergetics are presented. From the perspective of unified cell bioenergetics certain subsequent stages of cancer development, from initiation stage, through transformation to metastasis, are analyzed. Here we show that after transformation, cancer cells are permanently exposed to reactive oxygen species, that causes continual random DNA mutations and as a result genome and chromosomal destabilizations. The modern cancer attractor hypothesis has been extended in explaining cancer development. Discussion is conducted in light of current cancerogenesis research, including bioenergetic cancer initiation, the somatic mutation theory and the tissue organization field theory. In the article reasons complicating the discovery of patterns of cancer genome changes and cancer evolution are presented. In addition certain cancer therapeutic aspects are given attention to.

Evolutionary Views of Tuberculosis: Indoleamine 2,3‐Dioxygenase Catalyzed Nicotinamide Synthesis Reflects Shifts in Macrophage Metabolism

“…The field of immunometabolism has made some extraordinary advances in recent years, converging on the role of mitochondria in the balance between health and disease. [ 29,39–41 ]…”

“…Historically, Warburg and others postulated the switch from oxidative phosphorylation (involving the full Krebs cycle and electron transport chain within the mitochondrion) to aerobic glycolysis as the root cause of malignancy. [ 40,81–83 ] Subsequently, Warburg metabolism in cancer has been considered merely a malignancy‐associated phenomenon. [ 84 ] Despite the limitations on the amount of adenine triphosphate (ATP) that can be produced through glycolysis alone (2 ATP molecules produced per glucose molecule compared with 36 ATP molecules via the Krebs cycle and oxidative phosphorylation), rapidly dividing cells undergo glycolysis without completing electron transfer to oxygen, even when oxygen is available to them.…”

“…[ 113 ] In a macaque TB model, IDO inhibition reduced mycobacterial burden and pathology. [ 114 ] Other relevant strategies have included using inhibitors targeting mycobacterial tryptophan synthesis [ 40,115 ] or the mycobacterial NAD + synthesis or recycling pathways. [ 50,72,77 ]…”

Nicotinamide pathways as the root cause of sepsis – an evolutionary perspective on macrophage energetic shifts

“…Avenues of investigation from both aging research as well as immunology are converging attention on a pathway which connects immune responses with aging [8][9][10][11][12][13]. Nicotinamide adenine dinucleotide (NAD) in its oxidized (NAD + ) and reduced (NADH) forms, plays an essential role in energy metabolism in every eukaryotic cell [14,15].…”

Genome Attractors as Places of Evolution and Oases of Life

“…Unified cell bioenergetics allows the universal interpretation of several main cell bioenergetic effects (inter alia, the Pasteur, Crabtree, Kluyver, glucose effects) that can occur during bioprocesses and certain diseases (diabetes, cancer, heart diseases) based on the intramitochondrial NADH (mtNADH) level [19][20][21][22][23][24][25]. Mitochondria control both the life and death of cells [19,26]. Moreover, it is known that in almost every disease, an increased lactate concentration is caused by a shift in mitochondrial activity [27,28].…”