Introduction to the TCA Cycle

The TCA cycle, shown in Figure , differs from glycolysis in that it has no beginning or end. Whereas adding a given amount of a glycolytic intermediate results in the synthesis of an equimolar amount of pyruvate, the addition of a given amount of an intermediate of the TCA cycle results in a greater than equimolar amount of pyruvate consumed. This catalytic behavior of the pathway intermediates was one of the more important pieces of evidence that led Hans Krebs to propose that the oxidation of pyruvate was a cyclical pathway. Although the individual molecules of the TCA cycle do not regenerate, each turn of the cycle regenerates an equimolar amount of the acceptor molecule.

The TCA cycle can be thought of as comprising three phases:

Entry phase: Pyruvate is decarboxylated and the remaining 2‐carbon unit is joined to a 4 carbon dicarboxylic acid to make citrate, which is then rearranged into another 6‐carbon acid, isocitrate: 

Oxidative phase: Isocitrate is decarboxylated, releasing CO 2 and reducing equivalents. The product of this reaction is itself decarboxylated to yield a 4‐dicarboxylic acid, CO 2, and reducing equivalents. The reducing equivalents, mostly as NADH, are then transferred through the cytochromes to an electron acceptor, for example, oxygen:


Regeneration phase: The 4‐carbon dicarboxylic acid is rearranged to regenerate the acceptor of 2‐carbon units. More reducing equivalents are produced: