Curative enzyme

Some haloperoxidases contain vanadium and a review of vanadium peroxidases has been given (Butler 1998). The structure of the vanadium enzyme in the terrestrial fungus Cur-vularia inaequalis has been determined by x-ray analysis (Messerschmidt et al. 1997), and the apochloroperoxidase possesses, in addition, phosphatase activity that can be rationalized on the basis of the isomorphism of phosphate and vanadate (Renirie et al. 2000). 

Various drugs have been used to treat diarrhea (Table 23-4). These drugs are grouped into several categories antimotility, adsorbents, antisecretory compounds, antibiotics, enzymes, and intestinal microflora. Usually, these drugs are not curative but palliative. 

Cytochrome c oxidase is an enzyme that couples the one-electron oxidation of cytochrome c to the four-electron reduction of 02 and is thus a crucial component of respiration. Cytochrome c contains the redox-active heme c, while cytochrome c oxidase contains a dinuclear Cua redox site in subunit II and three redox-active sites in subunit I heme a, heme a3, and Cur. It is believed that heme a is an electron-transfer site, while heme a3 and Cur function together at the 02 reduction site. 

Mechanism of Action An enzyme that activates the fibrinolytic system by converting plasminogen to plasmin, an enzyme that degrades fibrin clots. Acts indirectlybyform ing a complex with plasminogen, which converts plasminogen to plasmin. Action oc-curs within the thrombus, on its surface, and in circulating blood. Therapeutic Effect Destroys thrombi. 

The TET-induced inhibitory influence on cyclic 3 ,5 -AMP phosphodiesterase (PDE) activities precedes edema formation in the rat brain [74]. lb clarify the mechanism of the protective action of EGb against TET-toxidty in rats, in vitro and ex vivo effects of EGb on PDE activities of cerebral tissue were investigated [75]. Higher concentrations of EGb (5-250 mg/L) inhibited the PDE activity in the brain in normal rats, whereas lower concentrations (0.25-4.0 mg/L) of EGb enhanced the activity of the enzyme. The inhbitory effect of TET on the high affinity PDE activity (measured with 0.25 ftM cyclic AMP) of the brain was diminished in the presence of low EGb concentrations. Furthermore, preventive and curative treatment of 1 El-poisoned rats with EGb (100 mg/kg, p.o., for 7 days) prevented both the formation of edema and the fall of PDE activity induced by TET alone. These results suggested the antiedema action of EGb might be partly associated with its modulating influences on cellular cyclic AMP levels via activation of membrane-bound PDE. 

Many claims have been made for manganese salen derivatives, from the hotly debated report that they extend the lifespan of nematode worms [27, 28] to curative properties in cases of lung damage [29], Unfortunately the compounds suffer from the same problems as other simple enzyme mimics in that they are not shielded from deactivation mechanisms by a protein shell. Furthermore they can also act as prooxidants through mechanisms such as the following ... 

Third, after contact with BAS the microorganisms become sensitive to the action of proteolytic enzymes and cationic and anionic SAS, such as bile acids and phospholipids that is to natural components of intestinal and gastric juices. The high affinity of BAS to microorganisms, and its influence on processes of vital activity of microorganisms, provides an explanation for mechanisms of its curative effect. The appearance of infectious diseases and their progress are directly dependent on the contagious dose and number of bacteria that are accumulated in an intestine in the course of colonization. 

CD50, Curative dose for 50% of mice following subcutaneous dosing Ih and 5h post infection strains producing plasmid-mediated yS-lactamase Richmond-Sykes classification of enzymes. Clavulanic acid alone was ineffective at 50 mg/kg. For abbreviations, see footnote to Table 6.1. 

Organisms containing vanadate-dependent haloperoxidases. The enzymes from the algae A. nodosum and Cor. officinalis and the lichen X parietina are hromoperoxidases, and the fungal enzyme (Cur. inaequalis, shown with sporangia) is a chloroperoxidase. 

Single-crystal X-ray structures are available for the enzymes isolated from A nodosum (holoenzyme),[ " l Cur. inaequalis (apoenzyme and tungstate variant,sulfate variant, azide form of the holoenzymel and the native holoenzyme plus its peroxo formP ]), Cor. officinalis (phosphate variant) and Cor. pilulifera (phosphate variant). The Cor. pilulifera peroxidase also contains a structural Ca + ion. The enzymes from the red algae are hexamers of dimers with 595 amino acids per monomeric subunit, the... 

A. nodosum enzyme is a homodimer (551 amino acids) and the Cur. inaequalis enzyme is a monomer constituting 609 amino acids. The tertiary structures are dominated by helical elements, arranged in bundles of four helices. Figure 4.15 (left) provides a schematic view of the fungal VCIPO. The dodecameric VBrPO from Cor. officinalis attains cubic symmetry, with each of the faces of the cube occupied by a dimer. This arrangement leaves a cavity of 26 A in diameter the outer diameter of the protein amounts to 150 A. The monomeric Cur. inaequalis enzyme has a cylindrical shape with the dimensions 80 X 55 A. 

The overall amino acid homology between the three types of haloperoxidases is comparatively low there is 33% identity between the A. nodosum and Cor. officinalis enzymes and 21.5% identity between the A. nodosum and the Cur. inaequalis enzymes. There is, however, close homology in the active site regions. In the algal bromoper-oxidases, the active site is situated at the bottom of a substrate cleft or funnel, 20 A deep and 14 A wide in the case of Cor. officinalis, and 15 A deep and 12 (entrance) to 8 A (bottom) wide in the case of A. nodosum. The inside of the funnel is lined by hydrophilic and hydrophobic amino acids, allowing, in principal, access of a broad variety of substrates. 

The active sites of the bromoperoxidase from A. nodosum (a), the chloroperoxidase from Cur. inaequalis (b) and its peroxo form (c). In (c), amino acids proposed to play a role in the activation of peroxide are indicated. Tryptophan (Trp350/Trp338) is replaced by arginine (Arg395) in the bromoperoxidase from the red alga Cor. officinalis. The structure in (d) is based on XAS and EPR data for the reduced, inactive form of the A. nodosum enzyme. See Table 4.5 for structure parameters and references. 

In some experiments concerned with the mechanism by which tryptophan acted to improve hepatic protein synthesis after toxic injury, the ability of tryptophan to stimulate hepatic mRNA synthesis, nucleocytoplasmic translocation of RNA in vitro, and nuclear envelope nucleoside triphosphatase activity after hepatotoxic injury was measured.188 Nucleoside triphosphatase (Mg2+-dependent adenosine triphosphatase, EC 3.6.1.3.1) was assayed since it is present in mammalian liver nuclear envelopes,224 and there is evidence that this enzyme is involved in nucleocytoplasmic translocation of RNA.221 All of these parameters were elevated significantly by tryptophan after agents such as actinomycin D, cordycepin, ethionine, puromycin, and hypertonic NaCl demonstrated a curative effect by tryptophan, but not after tryptophan following CC14, NaF, and sparsomycin demonstrated no improvement with tryptophan. These findings emphasized the importance of the role that tryptophan plays in stimulating the availability of cytoplasmic... 

It is hoped that, in the future, Gaucher s disease, currently a model of enzyme replacement therapy, will prove to be a model of a curative form of gene transfer therapy for inherited metabolic disorders. In this case CD34 cells from the patient s blood will be genetically corrected in vitro and transplanted back into the patient. 

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