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The primary energy-releasing pathways of metabolism involve the breakdown and synthesis of carbohydrates, lipids, and amino acids. The central metabolic pathway of the cell is the tricarboxylic acid (TCA) cycle, sometimes called the Krebs cycle after the German/British biochemist who recognized that the reactions of a limited number of dicarboxylic and tricarboxylic acids involved intermediates that were regenerated in each reaction series. Other pathways were known before that time, but they all seemed to have a definite beginning (substrate) and end (product). In contrast, 2-carbon compounds enter the Krebs cycle by reacting with a 4-carbon dicarboxylic acid to make a 6-carbon tricarboxylic acid, citric acid. (Another name for the tricarboxylic acid cycle is the citric acid cycle. This term refers to the most important step for the entry of carbon-containing compounds into the cycle.) Citric acid is then oxidized in two successive steps, removing one carbon at a time, to make a four-carbon dicarboxylic acid, which then is metabolized to the first acceptor. The carbon count is therefore:

This shorthand describes the synthesis of a six-carbon compound from four- and two-carbon substrates and the subsequent breakdown of the six-carbon compound. This numerical shorthand will be used throughout this series.

The breakdown of citric acid involves the oxidation of carbon to CO₂ and the reduction of a cofactor, NAD, which then sends its electrons through a series of reactions to a terminal electron acceptor. In terrestrial animals and plants, this acceptor is oxygen, which forms water. Other organisms, especially bacteria, can use a variety of terminal electron acceptors—for example, sulfur or organic compounds.

Breakdown of carbohydrates and lipids leads to the synthesis of two-carbon intermediates of the Krebs cycle. Breakdown of amino acids leads to the synthesis of either two- or four-carbon compounds that can enter the Krebs cycle. Purines and pyrimidines are generally not broken down but rather are recycled by animals and plants, although purines and pyrimidines can be broken down into carbon dioxide and ammonia by plants and bacteria.

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