| STEREOSPECIFICITY OF ENZYMES |
| Aconitase catalyzes isomerization at the oxaloacetate end of the citrate molecule. However, citrate has no asymmetric centers; it is achiral. How does aconitase know 'which end is up?' The answer lies in the nature of citrate binding to the active site of aconitase, a process known as three-point attachment. As shown in Figure 13.10, because of the geometry of the active site of aconitase, there is only one way for citrate to bind. This 'three-point binding' places the oxaloacetate carbons in the proper orientation for the isomerization reaction, while the carbons derived from acetyl-CoA are excluded from the active site. Although citrate is a symmetric or achiral molecule, it is termed 'prochiral' because it is converted to a chiral molecule, isocitrate. Similar types of three-point binding processes are involved in transaminase reactions that produce exclusively L-amino acids from ketoacids. The reduction of the nicotinamide ring by NAD(H)-dependent dehydrogenases is also stereospecific. Some dehydrogenases place the added hydrogen exclusively on the front face of the nicotinamide ring (viewed with the amide group to the right), while others add hydrogen only to the back face (see Fig. 13.11). |
| Aconitase is an iron-sulfur protein (Chapter 8) that isomerizes citrate to isocitrate through the enzyme-bound intermediate cis-aconitate. The two-step reaction is reversible and involves dehydration followed by hydration. Although citrate is a symmetric molecule, aconitase works specifically on the oxaloacetate end of citrate, not the end derived from acetyl-CoA (Fig. 13.9). Such stereochemical specificity occurs because of the geometry of the active site of aconitase (Fig. 13.10).
A cytosolic aconitase, known as IRE-BP (iron-response element binding protein) functions in the regulation of iron storage.
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