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Regulation of the Citric Acid Cycle:- Substrate Channeling through Multienzyme Complexes May Occur in the Citric Acid Cycle

المؤلف:  David L. Nelson، Michael M. Cox

المصدر:  Lehninger Principles of Biochemistry

الجزء والصفحة:  p622-623

2026-06-11

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Regulation of the Citric Acid Cycle:- Substrate Channeling through Multienzyme Complexes May Occur in the Citric Acid Cycle

Although the enzymes of the citric acid cycle are usually described as soluble components of the mitochondrial matrix (except for succinate dehydrogenase, which is membrane-bound), growing evidence suggests that within the mitochondrion these enzymes exist as multi enzyme complexes. The classic approach of enzymology—purification of individual proteins from extracts of broken cells—was applied with great success to the citric acid cycle enzymes. However, the first casualty of cell breakage is higher-level organization within the cell—the noncovalent, reversible interaction of one protein with another, or of an enzyme with some structural compo nent such as a membrane, microtubule, or microfilament. When cells are broken open, their contents, including enzymes, are diluted 100- or 1,000-fold (Fig. 16–19). Several types of evidence suggest that, in cells, multi enzyme complexes ensure efficient passage of the product of one enzyme reaction to the next enzyme in the pathway. Such complexes are called metabolons. Certain enzymes of the citric acid cycle have been isolated together as supramolecular aggregates, or have been found associated with the inner mitochondrial mem brane, or have been shown to diffuse in the mitochondrial matrix more slowly than expected for the individual protein in solution. There is strong evidence for substrate channeling through multienzyme complexes in other metabolic pathways, and many enzymes thought of as “soluble” probably function in the cell as highly organized complexes that channel intermediates.

FIGURE 16–19 Dilution of a solution containing a noncovalent protein complex—such as one consisting of three enzymes—favors dis sociation of the complex into its constituents.