Detoxification enzyme

Some metals can be converted to a less toxic form through enzyme detoxification. The most well-described example of this mechanism is the mercury resistance system, which occurs in S. aureus,43 Bacillus sp.,44 E. coli,45 Streptomyces lividans,46 and Thiobacillus ferrooxidans 47 The mer operon in these bacteria includes two different metal resistance mechanisms.48 MerA employs an enzyme detoxification approach as it encodes a mercury reductase, which converts the divalent mercury cation into elemental mercury 49 Elemental mercury is more stable and less toxic than the divalent cation. Other genes in the operon encode membrane proteins that are involved in the active transport of elemental mercury out of the cell.50 52... 

The breakdown of chemicals in the body (biotransformation) by enzymes. (Detoxification refers to the removal of a toxic chemical from the body.) digitalis... 

Biochemical mechanisms have also been suggested to explain the symptoms associated with MCS. One hypothesis states that individuals who have genetically or nutritionally defective enzyme detoxification systems might be more susceptible to exposure to low levels of chemicals. Another hypothesis states that chemicals may cause blood vessel constriction, inflammation, or leaking in multiple organ systems which would produce various combinations of symptoms. 

The treated toxins are sometimes referred to as formol toxoids. Toxoid vaccines are very effective in the prevention of those diseases such as diphtheria, tetanus, botulism and clostridial infections of farm animals, in which the infecting bacteria produce disease through the toxic effects of secreted proteins which enzymically modify essential cellular components. Many of the clostridial toxins are lytic enzymes. Detoxification is also required for the pertussis toxin component of acellular pertussis vaccines. 

Bipolarity. Following toxic exposure, the body develops a bipolar response of a stimulatory phase followed by a depressive phase, with the induction of immune and enzymatic detoxification systems. If the toxic insult is great enough, the induced immune and enzyme detoxification systems are depleted or depressed by overutilization and overstimulation. Bipolarity helps explain why symptoms may not be obviously related to exposures, but ensue following later exposures. 

Presence of endogenous quenchers or free radical scavengers and enzyme detoxification systems that could stop or retard these photochemical reactions... 

Certain genetic and physical factors predispose individuals to greater sensitivity to PCBs (Table 16-3). Individuals who do not detoxify and excrete PCBs rapidly have the greatest risk (Calabrese 1978). Numerous studies of the development of infants exposed to background PCB suggest that immature enzyme detoxification systems render young persons susceptible to PCB neurotoxicity. 

Active immobilized enzyme detoxification of pesticides in production waste-waters Active immobilized enzyme deacylation of benzylpenicillin in a continuous four-stage stirred-tank reactor Investigation of properties of the active immobilized enzyme Investigation of new carriers for enzyme immobilization... 

Fig. 15. Fate of PA AT-oxides ingested by vertebrates and insects. Following reduction of the N-oxide in the gut and passive uptake of the alkaloid free base, bioactivation occurs in all organisms which possess cytochrome P450 enzymes. Detoxification by N-oxidation is possible in vertebrates with an efficient multisubstrate flavin monooxygenase (FMO). Specialized herbivorous lepidopterans apply the same strategy they developed a substrate specific enzyme, senecionine AT-oxygenase (SNO) and keep the non-toxic PA-AT-oxides for their own benefit...

Adaptation addresses the body s ability to increase body load without apparent symptoms, despite the fact that continued toxic exposures may continue to damage the immune and enzyme detoxification systems (xenobiotic metabolic processes). At some point, such continued accumulation results in end-organ failure. 

Biochemical individuality of response is the individual s uniqueness. This uniqueness of response depends on the differing quantities of carbohydrates, fats, proteins, enzymes, vitamins, minerals, immune and enzyme detoxification parameters with which an individual is equipped to handle pollutant insults. These variations determine an individual s ability to process the noxious substances he encounters.. . . Thus, a group of individuals may be exposed to the same pollutant. One person may develop arthritis, one sinusitis, one diarrhea, one cystitis, one asthma, and one may remain apparently unaffected. 

Care should be exercised when attempting to interpret in vivo pharmacological data in terms of specific chemical—biological interactions for a series of asymmetric compounds, particularly when this interaction is the only parameter considered in the analysis (10). It is important to recognize that the observed difference in activity between optical antipodes is not simply a result of the association of the compound with an enzyme or receptor target. Enantiomers differ in absorption rates across membranes, especially where active transport mechanisms are involved (11). They bind with different affinities to plasma proteins (12) and undergo alternative metaboHc and detoxification processes (13). This ultimately leads to one enantiomer being more available to produce a therapeutic effect. 

L-Tyrosine metabohsm and catecholamine biosynthesis occur largely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andhpid metabohsm. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bUe acids and the detoxification process of aromatic dmgs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabohsm related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

Two important pathways for catecholamine metaboHsm are 0-methylation by COMT, which is cytoplasmicaHy localized, and oxidative deamination by the mitochondrial localized enzyme MAO. There are large amounts of MAO in tissues such as the fiver and the heart which are responsible for the removal of most of the circulating monoamine, including some taken in from the diet. Tyramine is found in high concentrations in certain foods such as cheese, and in wine. Normally, this tyramine is deaminated in the fiver. However, if MAO is inhibited, the tyramine may then be converted into octopamine [104-14-37] which may indirecdy cause release of NE from nerve terminals to cause hypertensive crisis. Thus MAO, which is relatively nonspecific, plays an important role in the detoxification of pharmacologically active amines ingested from the diet. 

Biocatalytic access to both antipodal sulfoxides was exploited in total syntheses of bioactive compounds, which is outlined in some representative examples. Biooxidation of functionalized dialkyl sulfides was utilized in the direct synthesis of both enantiomers of sulforaphane and some analogs in low to good yields and stereoselectivities (Scheme 9.27) [206]. This natural product originates from broccoli and represents a potent inducer of detoxification enzymes in mammalian metabolism it might be related to anticarcinogenic properties of plants from the cruciform family. All four possible stereoisomers of methionine (R = Me) and ethionine sulfoxides... 

Metabolic pathways containing dioxygenases in wild-type strains are usually related to detoxification processes upon conversion of aromatic xenobiotics to phenols and catechols, which are more readily excreted. Within such pathways, the intermediate chiral cis-diol is rearomatized by a dihydrodiol-dehydrogenase. While this mild route to catechols is also exploited synthetically [221], the chirality is lost. In the context of asymmetric synthesis, such further biotransformations have to be prevented, which was initially realized by using mutant strains deficient in enzymes responsible for the rearomatization. Today, several dioxygenases with complementary substrate profiles are available, as outlined in Table 9.6. Considering the delicate architecture of these enzyme complexes, recombinant whole-cell-mediated biotransformations are the only option for such conversions. E. coli is preferably used as host and fermentation protocols have been optimized [222,223]. 

There is a second type of cholinesterase called butyrylcholinesterase, pseudocholinesterase, or cholinesterase. This enzyme is present in some nonneural cells in the central and peripheral nervous systems as well as in plasma and serum, the liver, and other organs. Its physiologic function is not known, but is hypothesized to be the hydrolysis of esters ingested from plants (Lefkowitz et al. 1996). Plasma cholinesterases are also inhibited by organophosphate compounds through irreversible binding this binding can act as a detoxification mechanism as it affords some protection to acetylcholinesterase in the nervous system (Parkinson 1996 Taylor 1996). 

Livingstone, D.R. (1985). Responses of the detoxification/toxication enzyme system of molluscs to organic pollutants and xenobiotics. Marine Pollution Bulletin 16, 158-164. 

TALALAY p (1991) Chemical Protection Against Cancer by Inducation of Electrophile Detoxification (phase 2) Enzymes Cellular Molec Targets Chemoprev, 1-11. 

STAACK R, KINGSTON s, WALLiG M A and JEFFERY E H (1998) A Comparison of the individual and collective effects of four glucosinolate breakdown products from Brussels sprouts on induction of detoxification enzymes , Toxicol Appl Pharmacol, 149 17-23. 

NHO c w and JEFFERY E (2001) The synergistic upregulation of phase II detoxification enzymes by glucosinolate breakdown products in cruciferous vegetables , Toxicol Appl Pharmacol, 174 146-52. 

Tocotrienols, gamma Oryzanol Phosphatidyl chohne Antioxidants Controls liver cirrhosis and helps in effective liver detoxification (Bruni, 1988). Protectant against hver damage (Kidd, 1996). Antioxidant enzymes prevent hpid peroxidation and helps protecting the liver cells from damage. 

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