Detoxification reactions

Detoxifica.tlon. Detoxification systems in the human body often involve reactions that utilize sulfur-containing compounds. For example, reactions in which sulfate esters of potentially toxic compounds are formed, rendering these less toxic or nontoxic, are common as are acetylation reactions involving acetyl—SCoA (45). Another important compound is. Vadenosylmethionine [29908-03-0] (SAM), the active form of methionine. SAM acts as a methylating agent, eg, in detoxification reactions such as the methylation of pyridine derivatives, and in the formation of choline (qv), creatine [60-27-5] carnitine [461-06-3] and epinephrine [329-65-7] (50). 

Alternative metabolic pathways involve ring-oxidation and peroxidation of arylamines. Although ring-oxidation is generally considered a detoxification reaction, an electrophilic iminoquinone (X) can be formed by a secondary oxidation of the aminophenol metabolite (18,19). Lastly, reactive imines (XI) can be formed from the primary arylamines by peroxidase-catalyzed reactions that involve free radical intermediates (reviewed in 20). 

Hence, the overall reaction for iron oxidation and hydrolysis at the ferroxidase centre, followed by further hydrolysis and migration to the core nucleation sites consists of two reactions, the protein-catalysed ferroxidase reaction itself and the Fe(II) plus H202 detoxification reaction (Equations (19.7) and (19.8), respectively) ... 

The biotransformations involved in the study of drug metabolism (Fig. 1) are mainly represented by detoxification reactions, due to the fact that drugs (mainly hydrophobic substances easily permeating through the cell membrane)... 

Chapter 19) Adrenal cortex Liver Fatty acid synthesis Elongation of fatty acids (Chapter 11) Desaturation of fatty acids Detoxification reactions... 

A specific example involving aflatoxins is shown in Box 6.8. We shall see other examples of glutathione reacting as a nucleophile in detoxification reactions, where conjugation is not the result of nucleophilic substitution. For example, it might be nucleophilic addition to an electrophile such as an unsaturated carbonyl compound (see Box 10.20). 

There is now a wide consensus that HA is a product of normal metabolism, and that its toxicity, and that of substituted HAs, is manifested only at concentrations well above those expected when HA is produced as a result of normal cell metabolism. However, despite the fact that N-hydroxylation is a key detoxification reaction for various drugs, the lack of convincing direct in vivo measurements of HA itself in healthy individuals does not permit a definitive conclusion as to its normal endogenous levels as a harmless species in mammalian cells. 

NADP Loose Niacin (B3) Same as NAD but used mainly in biosynthetic pathways and detoxification reactions... 

Drug conjugations were once believed to represent terminal inactivation events and as such have been viewed as "true detoxification" reactions. However, this concept must be modified, because it is now known that certain conjugation... 

Recall in our discussion of routes of biotransformation we considered species differences using malathion as an example. Insects convert this compound to its toxic oxidation product more quickly than they detoxify it by hydrolysis. Humans do the conversions in the opposite priority. However, the insects which might be different from the general population and perform detoxification reactions at a faster rate would survive pesticide application and their "resistant" genes would be selectively passed on to the next generations. 

Participation as a cofactor in an number of enzymatic reactions, including the synthesis of collagen, carnitine, and norepinephrine the metabolism of tryptophan, tyrosine, histamine, and cholesterol the amidation of neuropeptides and detoxification reactions in the liver... 

Bioinorganic chemistry will surely develop in an even wider area than it has thus far. Attention is likely to increase for studies on nonmetals, such as Se and As and their roles in, e.g., detoxification reactions. In addition, studies on elements such as aluminum (a possible causative factor in dialysis dementia and related to Alzheimer disease, senile dementia) and other abundant earth crust metals will increase. The role of bioinorganic catalysis to make and keep our environment clean has been mentioned in many of the previous chapters. It is to be expected that future catalytic processes, based on and derived from biological ones, will be as clean as possible, producing useful, harmless, and biodegradable products for the world. 

Results with intimately mixed oxides show that further enhancement of reactivity for these detoxification reactions can be achieved. Mixed metal oxide systems of AP-Mg0-Al203 and AP-Ca0-Al203 are better at destructively adsorbing paraoxon than AP-MgO, AP-CaO and AP-A1203 by themselves.10 Sulfated mixed metal oxides also show further improved adsorption suggesting that increasing the acidity of the sample enhances adsorption.10... 

The above reactions may be considered to be detoxification reactions that permit various life forms to survive in an oxygen atmosphere. Strictly anaerobic microorganisms lack superoxide dismutases and cannot survive long in air. To them, oxygen is toxic. 

Cysteine is considered a nonessential nutrient because it can be synthesized from methionine via the transsulfuration pathway (Figs. 21-1 and 21-2). Production of cysteine is metabolically important because it serves as a source of sulfur for incorporation into proteins and detoxification reactions. A lack of cysteine needed for incorporation into the structural protein collagen may be responsible for the musculoskeletal abnormalities seen in patients with CBS deficiency. A major metabolic use of cysteine is in the production of glutathionine (y-glutamylcysteinylglycine), an important antioxidant. Another important pathway for cysteine metabolism is its oxidation to cysteinesulfinate, which serves as a precursor for taurine, an amino acid that stabilizes cell membranes in the brain. 

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