Phenol oxidases inhibitors

A phenol oxidase from the fish cestode, Penetrocephalus ganapatii, has been characterised bio-chemically and has been shown to have a pH optimum of 7.4 (Fig. 7.9) (362). Its activity with three different substrates, dopamine, adrenaline (= epinephrine) and dopa are shown in Table 7.4 and Fig. 7.10 the action of various inhibitors is shown in Table 7.5. The Michaelis constant for dopamine was 189 p.M and the enzyme was stable between 20 and 40°C. The action of various inhibitors was also studied. 

Table 7.5. Effect of various inhibitors on the phenol oxidase of Penetrocephalus ganapatii. (Data from Jayabaskaran Ramalingam,...

The appearance and increase of cyclopenase activity (D 8.4.2) during conidiospore maturation in Penicillium cyclopium cannot be prevented by cycloheximide (D 3.3.7), an inhibitor of translation, in concentrations which suppress protein biosynthesis. This indicates that a proenzyme exists which is formed during an earlier stage of development. The mechanism of transformation of the cyclopenase proenzyme into active cyclopenase is still unclear. In similar cases, however, e.g., the activation of prochitin synthase in Saccharomyces cerevisiae and of a phenol oxidase zymogen (C 2.3.1) in the hemolymph of Calliphora larvae, the active enzyme is formed by proteolytic processing of a proteinogen. 

Gunata, Y.Z., Sapis, J.C. Moutounet, M. (1987). Substrates and aromatic carboxylic-acid inhibitors of grape phenol oxidases. Plytochemistry, 26,1573-1575. 

Biological pretreatments include the use of specific microorganisms or oxidative enzymes that remove or transform toxic substances in the hydrolysates to innocuous forms (Mussatto and Roberto, 2004b). Jonsson et al. (1998) demonstrated efficient detoxification of willow hydrolysates using laccase (a phenol oxidase) and lignin peroxidase enzymes isolated from the white rot fungus, Trametes versicolor. The mechanism of toxin removal was postulated to involve oxidative polymerization of monoaromatic phenolic compounds, which were identified as potent inhibitors of hemieellulosic fermentation. 

Various phenolic acids have been reported to inhibit IAA oxidase (9, 52,120), and other phenols may act as cofactors of IAA oxidase (144). In general, the cofactors of IAA oxidase are monophenols, whereas the inhibitors of the system are polyphenols, with o-dihy-droxyphenols being the most inhibitory (52, 65). Unsaturated lactones have also been reported to inhibit IAA oxidase (2, 52). 

Phenolic compounds naturally occurring in plants have induced many physiological responses that duplicate those reported for ozone and/or peroxyacetylnitrate (PAN). Chlorogenic acid is a competitive inhibitor of lAA-oxidase (35) and plant growth is adversely affected by increased concentrations of auxins (36). Concentrations of chlorogenic acid are increased in tobacco tissue exposed to ozone ( ) Phenols inhibit ATP synthesis (37), oxidative phosphorylation ( ) and SH enzyme activity (27) they increase respiration (38), reduce CO2 fixation (22), modify both membrane permeability (40) and oxidation rate of reduced NADH... 

The free phenols that are produced in the brain (when they break off during the reaction with AChE), are related to the drug selegiline (Fig. 12.8), which is a monoamine oxidase B (MAO-B) inhibitor, so that they also exhibit such inhibitory activity. MAO-B inhibitors are helpful in Parkinson s disease, mainly because they cause an increase in the level of dopamine, and are also antidepressants. These compounds are currently under investigation as treatment for Alzheimer s disease complicated by other cognitive deficits. 

Extrapolation of these results to the real world suggests that the simultaneous use of PPO/phenolics and proteinase inhibitors as bases of resistance against certain insects may be mutually incompatible. If one were to rely on proteinase inhibitors as a basis, the elimination of high levels of polyphenol oxidase in the plant would not guarantee antibiotic activity because high levels of dietary protein can abolish PI toxicity (89) Hence, the activity of PI, PPO and phenolics in situ may require the manipulation of multiple plant factors. 

Monoamine oxidase (MAO) inhibitors are contraindications to the use of the majority of analgesics and psychotropic drugs required for patient comfort. This would make a phenol peel almost unbearable for a patient on MAO inhibitors, who is, by definition, psychologically imstable. 

Adrenaline is contraindicated in cases of diabetes, hyperthyroidism, serious heart arrhythmias and coronary insufficiency or in combination with beta-blockers or monoamine oxidase (MAO) inhibitors. Lidocaine with adrenaline has a very rapid onset of action. Its duration of action is longer than that of lidocaine without adrenaline. However, inadvertent injection of a lidocaine-adrenaline solution into the vessels located near the nerve trunks increases the heart rate (immediate sinus tachycardia at over 130 beats per minute, spontaneously reversible in around 15 minutes) and increases ventricular excitability (risk of fibrillation). It can trigger angina attacks that may lead to a heart attack. It is therefore preferable not to use adrenaline before a full-face phenol peel. 

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