The Bob Painter debates at the Radiation Research Society’s annual meeting “For” and “Against” stances in relation to the propositions that “Cancer is fundamentally a metabolic disease”. The "horse and the cart" [[link to our web page describing the detail]] provided the analogy used "For" the proposition that mitochondrial defects and metabolic oxidative stress drive the genetic changes associated with senescence as well as cancer related death.

L to R Joshua Schoenfeld (the horse),  John Ward (UCSD; moderator), Bryan Allen (the cart), Douglas Spitz (David of David and Goliath).

Figure 1

Using the analogy of a horse and a cart, the “horse” of metabolism pulls the “cart” of gene expression via the flow of electrons from metabolic processes to signaling pathways allowing for the coordinate regulation of living systems.

Figure 1, the horse and the cart

Figure 2

Unfortunately, due to the inefficiency of these oxidation reactions they generate small amounts of waste products. These are formed from one-electron reductions of O2 (electron leak) leading to the formation of reaction oxygen species (ROS; i.e., superoxide and hydrogen peroxide) that cause oxidative damage. 

Figure 2, the horse and the cart

Figure 3

This inefficiency in metabolism slowly weakens the structure (genetic integrity) of the cart, negatively affecting intracellular communication as well all the processes necessary for the maintenance of normal cellular functions.

Figure 3, the horse and the cart

Figures 4 and 5

While ROS are required signaling molecules for living systems they also lead to the gradual accumulation of oxidative damage to the genome causing increased metabolic inefficiency as we age, accelerating the processes that lead to the onset of degenerative diseases associated with aging and cancer.

Figure 4, the horse and the cart

Figure 5, the horse and the cart