Oxidation of Fatty Acids:- The β-Oxidation Enzymes of Different Organelles Have Diverged during Evolution
Although the β -oxidation reactions in mitochondria are essentially the same as those in peroxisomes and glyoxysomes, the enzymes (isozymes) differ significantly between the two types of organelles. The differences apparently reflect an evolutionary divergence that occurred very early, with the separation of gram-positive and gram-negative bacteria.
In mitochondria, the four -oxidation enzymes that act on short-chain fatty acyl–CoAs are separate, soluble proteins (as noted earlier), similar in structure to the analogous enzymes of gram-positive bacteria (Fig. 17–15a). The gram-negative bacteria have four activities in three soluable subunits (Fig. 17–15b), and the eukaryotic enzyme system that acts on long-chain fatty acids— the trifunctional protein, TFP—has three enzyme activities in two subunits that are membrane-associated (Fig. 17–15c). The β -oxidation enzymes of plant peroxisomes and glyoxysomes, however, form a complex of proteins, one of which contains four enzymatic activities in a single polypeptide chain (Fig. 17–15d). The first enzyme, acyl-CoA oxidase, is a single polypeptide chain; the multifunctional protein (MFP) contains the second and third enzyme activities (enoyl-CoA hydratase and hydroxyacyl-CoA dehydrogenase) as well as two auxiliary activities needed for the oxidation of unsaturated fatty acids (D-3-hydroxyacyl-CoA epimerase and Δ3, Δ2 enoyl-CoA isomerase); the fourth enzyme, thiolase, is a separate, soluble polypeptide.
It is interesting that the enzymes that catalyze essentially the reversal of β oxidation in the synthesis of fatty acids are also organized differently in prokaryotes and eukaryotes; in bacteria, the seven enzymes needed for fatty acid synthesis are separate polypeptides, but in mammals, all seven activities are part of a single, huge polypeptide chain (see Fig. 21–7). One advantage to the cell in having several enzymes of the same pathway en coded in a single polypeptide chain is that this solves the problem of regulating the synthesis of enzymes that must interact functionally; regulation of the expression of one gene ensures production of the same number of active sites for all enzymes in the path. When each en zyme activity is on a separate polypeptide, some mechanism is required to coordinate the synthesis of all the gene products. The disadvantage of having several ac tivities on the same polypeptide is that the longer the polypeptide chain, the greater is the probability of a mis take in its synthesis: a single incorrect amino acid in the chain may make all the enzyme activities in that chain useless. Comparison of the gene structures for these proteins in many species may shed light on the reasons for the selection of one or the other strategy in evolution.
FIGURE 17–15 The enzymes of oxidation. Shown here are the different subunit structures of the enzymes of oxidation in gram-positive and gram-negative bacteria, mitochondria, and plant peroxisomes and glyoxysomes. Enz1 is acyl-CoA dehydrogenase; Enz2, enoyl-CoA hydratase; Enz3, L--hydroxyacyl-CoA dehydrogenase; Enz4, thiolase; Enz5, D-3-hydroxyacyl-CoA epimerase, and Enz6, Δ3, Δ2 -enoyl-CoA isomerase. (a) The four enzymes of β oxidation in gram-positive bacteria are separate, soluble entities, as are those of the short-chain-specific system of mitochondria. (b) In gram-negative bacteria, the four enzyme activities reside in three polypeptides; enzymes 2 and 3 are parts of a single polypeptide chain. (c) The very-long-chain-specific system of mitochondria is also composed of three polypeptides, one of which includes the activities of enzymes 2 and 3; in this case, the system is bound to the inner mitochondrial membrane. (d) In the peroxisomal and glyoxysomal β- oxidation systems of plants, enzymes 1 and 4 are separate polypeptides, but enzymes 2 and 3, as well as two auxiliary enzymes, are part of a single polypeptide chain, the multifunctional protein, MFP.
