Enzymes pathophysiology

Of the thousands of different enzymes present in the human body, those that fulfill functions indispensable to cell vitality are present throughout the body tissues. Other enzymes or isozymes are expressed only in specific cell types, during certain periods of development, or in response to specific physiologic or pathophysiologic changes. Analysis of the presence and distribution of enzymes and isozymes— whose expression is normally tissue-, time-, or circumstance-specific—often aids diagnosis. 

The theory underlying the pathophysiology of ischaemia-reperfusion injury, and the role of free radicals in this process has been discussed in detail above. The human colon contains relatively little XO (Parks and Granger, 1986) and so the arguments supporting a role for this enzyme in the pathogenesis of small bowel... 

Enzymes are excellent targets for pharmacological intervention, owing to their essential roles in life processes and pathophysiology. 

Fig. 2. Pathophysiological sequence of events in periodontal disease. Bacteria produce byproducts (e.g. toxins or enzymes) which, along with mucus, constantly form a sticky, colorless plaque on teeth. If not removed, plaque can harden and form bacteria-harboring tartar around teeth. Tissue that attaches the gums to the teeth can be destroyed by the irritants of plaque. If this is the case, gums pull away from the teeth and small pockets arise between the teeth and gums. The pockets then become filled with more plaque, deepen, and it becomes impossible to clean plaque out. At this stage the bone structure supporting teeth can actually be destroyed (courtesy of Drs J. Chavez and S.E. Zaragoza, El Paso Community College, Texas, USA).

The inactivation of enzymes containing the zinc-thiolate moieties by peroxynitrite may initiate an important pathophysiological process. In 1995, Crow et al. [129] showed that peroxynitrite disrupts the zinc-thiolate center of yeast alcohol dehydrogenase with the rate constant of 3.9 + 1.3 x 1051 mol-1 s-1, yielding the zinc release and enzyme inactivation. Later on, it has been shown [130] that only one zinc atom from the two present in the alcohol dehydrogenase monomer is released in the reaction with peroxynitrite. Recently, Zou et al. [131] reported the same reaction of peroxynitrite with endothelial NO synthase, which is accompanied by the zinc release from the zinc-thiolate cluster and probably the formation of disulfide bonds between enzyme monomers. The destruction of zinc-thiolate cluster resulted in a decrease in NO synthesis and an increase in superoxide production. It has been proposed that such a process might be the mechanism of vascular disease development, which is enhanced by diabetes mellitus. 

As mentioned earlier, extensive literature is dedicated to the study of functions of NO synthases under physiological and pathophysiological conditions. Much attention has been drawn to the capacity of these enzymes to generate free radicals. The mechanism of nitric oxide production by NO synthases was widely discussed and are presented in Figure 22.3 [147]. 

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