Textbook - BIOLOGICAL CHEMISTRY - Gubsky Yu.I. - 2000

Chapter II. GENERAL PRINCIPLES OF METABOLISM

CHAPTER 10. TRICARBOXYLIC ACID CYCLE

The Tricarboxylic Acid Cycle (Citric Acid Cycle, Krebs cycle) is a cyclic sequence of enzymatic reactions in which acetyl-CoA (CH₃-CO~S-KoA), the catabolic product of major metabolic fuels (CARBOHYDRATES, fats, Amino Acids), is oxidized to carbon dioxide with the generation of hydrogen atoms used to reduce primary acceptors of the mitochondrial Respiratory Chain—nicotinamide or Flavin Coenzymes.

10.1. GENERAL CHARACTERISTICS OF THE TRICARBOXYLIC ACID CYCLE

The tricarboxylic acid cycle (TCA cycle) is the common final pathway for the oxidative Catabolism of The Cell under aerobic conditions. The reactions and Enzymes of the TCA cycle are localized in the mitochondrial matrix and inner membrane. They are functionally and biochemically coupled with Mitochondrial Electron Transport chains, which utilize reducing equivalents from NADH (NADH + H⁺) and FADH₂ or FMNH₂ to reduce oxygen atoms and synthesize ATP via Oxidative Phosphorylation.

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Fig. 10.1. Hans Krebs (1900–1981). Worked in Germany; from 1933 at the universities of Cambridge, Sheffield, and Oxford (UK). Nobel Prize laureate (1953).

Scheme of TCA cycle functioning

The tricarboxylic acid cycle begins with the interaction (Condensation) of a two-carbon acetyl-CoA molecule (C₂) with a four-carbon (C₄) oxaloacetic acid (oxaloacetate), resulting in The formation of a six-carbon (C₆) citric acid molecule (citrate). As a result of subsequent multi-step transformations of tri- and dicarboxylic acids (TCA intermediates), oxaloacetate (C₄) is regenerated and two carbon dioxide molecules (C₂) are released.

Scheme of The Citric Acid Cycle operation.

Thus, coenzyme A is cleaved from acetyl-CoA (the "active form of acetic acid") as early as the first reaction of the TCA cycle. During the subsequent Reactions of the cycle, two carbon dioxide molecules and four pairs of hydrogen atoms (4 × 2H) are removed from citrate (an alternative name for the TCA cycle is the citrate cycle), allowing the overall equation of the TCA cycle to be represented as follows: