Biochemistry - The Chemical Reactions of Living Cells, Volume 2 - D. Metzler 1980

Organization of Metabolism: Catabolic Pathways
Fatty Acid Oxidation
Beta-Oxidation

Examining The Structure of the acyl-CoA molecule and taking into account known types of biochemical reactions, we find that the only rational pathway for further attack is The oxidation of the molecule by a flavoprotein. This leads to the abstraction of hydrogen atoms at the α- and β-positions, yielding an unsaturated acyl-CoA derivative (Fig. 9-1, a). One of the few possible reactions that the resulting unsaturated compound can undergo is nucleophilic addition at the β-position. The addition of Water (equation b) yields an alcohol, whose oxidation in the presence of NAD⁺ produces a ketone (equation c). This series of three reactions constitutes the well-known sequence of β-oxidation reactions. Figure 9-1 also illustrates another sequence, part of The Tricarboxylic Acid Cycle, in which succinic acid is converted into oxaloacetate.

By analogy with the existence of several activating Enzymes specific to Fatty acids with different chain lengths, There are also several acyl-CoA dehydrogenases that catalyze the reaction described by equation a (Fig. 9-1). All of them contain FAD. In each case, the reduced FADH₂ bound to the enzyme is subsequently reoxidized by a specialized electron-transferring flavoprotein [2, 3], which also contains FAD. It is believed that this protein transfers electrons to The inner mitochondrial membrane, where they enter the Mitochondrial Electron Transport system.

Upon completion of the β-oxidation reactions, the β-ketoacyl-CoA derivative is cleaved by thiolase [equation (9-2,6); see also equation (7-62)]. Here again, There is a family of enzymes specific to varying chain lengths. One of the products [equation (9-2)] is acetyl-CoA, which enters the tricarboxylic acid cycle and undergoes catabolic degradation to yield CO₂. The second product of thiolytic Cleavage is an acyl-CoA derivative that is shorter by two carbon atoms than the original molecule. It re-enters the β-oxidation cycle, with each turn of the cycle releasing a two-carbon fragment in the form of acetyl-CoA [equation (9-2)]. The process continues until the fatty acid chain is completely degraded. If the starting fatty acid contained an even number of carbon atoms in its straight chain, acetyl-CoA will be the sole product of β-oxidation. However, if the fatty acid molecule consists of an odd number of carbon atoms, the β-oxidation process terminates with The formation of propionyl-CoA.

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FIG. 9-1. Sequence of reactions in β-oxidation. Left: Oxidation of Fatty acid CoA derivatives; right: oxidation of succinate. Both reaction sequences take place inside the Cell/35.html">Mitochondria of Eukaryotic Cells and are catalyzed by specific enzymes; apparently, all of these enzymes (with one exception) are dissolved in the mitochondrial matrix. FAD* denotes a special type of FAD derivative found in succinate dehydrogenase (Ch. 8, Sec. B, 3); this enzyme is tightly bound to the inner mitochondrial membrane.