Are carcinogens electron acceptors? A novel hypothesis

Area of Science:

• Biochemistry
• Cancer Biology
• Metabolic Pathways

Background:

• Conventional cancer theories focus on genetic mutations.
• Emerging evidence suggests metabolic alterations precede genetic changes in carcinogenesis.
• Impaired cellular respiration, independent of mitochondrial function, is a key area of interest.

Purpose of the Study:

• To investigate the role of carcinogens as electron acceptors in disrupting cellular glycolysis.
• To propose a metabolic pathway initiated by carcinogens that promotes cancer development.
• To explore the hypothesis that metabolic stress precedes genetic and protein alterations in carcinogenesis.

Main Methods:

• Hypothesizing carcinogen activity as electron acceptors disrupting glycolysis.
• Describing the proposed metabolic pathway involving NAD+ regeneration.
• Linking metabolic stress to altered gene/protein expression and epigenetic changes.

Main Results:

• Carcinogens can act as electron acceptors, disrupting the normal glycolysis cycle.
• This disruption facilitates a continuous pool of NAD+ (nicotinamide adenine dinucleotide) via NADH oxidation, supporting glycolysis.
• Pyruvate conversion to lactate aids in sustaining NAD+ levels for ongoing glycolysis.

Conclusions:

• Carcinogens initiate cancer by disrupting cellular metabolism, specifically glycolysis.
• Metabolic stress induced by carcinogens may be a precursor to genetic and epigenetic alterations.
• Understanding this metabolic role of carcinogens offers new insights into cancer initiation.