Krebs cycle

The Krebs cycle, also known as the citric acid cycle or tricarboxylic acid (TCA) cycle, is the central oxidative pathway of metabolism, functioning as the primary engine for producing usable energy, carbon dioxide, and the electronically desaturated state of living matter. 3 Peat framed the cycle not merely as a biochemical sequence but as the core of cellular respiration whose efficient operation is the defining characteristic of health, while its disruption is the common denominator of degenerative disease. 2 The cycle processes acetyl-CoA, derived from the decarboxylation of pyruvate, through a series of reactions that generate NADH and carbon dioxide, with the latter being essential for oxygen delivery via the Bohr effect. 2

A critical regulatory point preceding the cycle is the enzyme pyruvate dehydrogenase (PDH), which converts pyruvate into acetyl-CoA. 2 Dinkov has described PDH as a rate-limiting "bridge" that, when blocked by factors such as a low mitochondrial NAD+/NADH ratio or deficiency of cofactors like vitamin B1 and magnesium, causes a backlog of glycolytic products. 2 This obstruction forces pyruvate to be reduced to lactic acid instead of entering the Krebs cycle, a metabolic signature Peat associated with cancer, inflammation, and the generalized stress state. 2 The cycle itself can also experience a buildup of electrons if the downstream electron transport chain is malfunctioning, a condition that activates fatty acid synthase to convert excess citric acid into fat as an emergency electron sink. 10

Peat emphasized that the cycle's intermediates serve as crucial junction points for managing excitotoxicity and cellular energy. He noted that the amino acids glutamate and aspartate, which act as excitatory signals, are normally consumed in the Krebs cycle as alpha-ketoglutarate and oxaloacetate, respectively. 6 A deficiency of carbon dioxide, resulting from impaired mitochondrial respiration, prevents the consumption of these excitatory amino acids and the synthesis of urea, creating a self-reinforcing loop of energy failure and cellular excitation that underlies conditions like epilepsy. 6 Szent-Györgyi, whose work was foundational to discovering the cycle, viewed the donation of electrons to cellular systems as the trigger for the active, contracted state, while the high-energy oxidative function of the cycle was the answer to restoring the cell to its stable, resting state. 8

Dinkov has elaborated on the therapeutic implications of manipulating the cycle, noting that certain alpha-keto acids like pyruvate and alpha-ketoglutarate are intermediates that, when supplemented, can theoretically speed up oxidative reactions. 4 He distinguishes these from beta-keto acids like acetoacetate, which can serve an oxidizing function, and beta-hydroxybutyrate, whose dangerous accumulation leads to diabetic ketoacidosis. 4 Furthermore, substances like salicylic acid (from aspirin) are understood to reactivate the Krebs cycle and electron transport chain, the two steps that are characteristically suppressed in cancer while glycolysis rages unchecked. 11 The cycle's proper function is thus the fulcrum of Peat's bioenergetic model, where the efficient oxidation of glucose to carbon dioxide is the fundamental process that sustains structure and prevents the activated, electron-rich state of pathology. 2