Oxidizing enzyme systems

An important function of certain carotenoids is their provitamin A activity. Vitamin A may be considered as having the stmcture of half of the P-carotene molecule with a molecule of water added at the end position. In general, all carotenoids containing a single unsubstituted P carotene half have provitamin A activity, but only about half the activity of P carotene. Provitamin A compounds are converted to Vitamin A by an oxidative enzyme system present in the intestinal mucosa of animals and humans. This conversion apparendy does not occur in plants (see Vitamins, VITAMIN a). 

Hurst (19) discusses the similarity in action of the pyrethrins and of DDT as indicated by a dispersant action on the lipids of insect cuticle and internal tissue. He has developed an elaborate theory of contact insecticidal action but provides no experimental data. Hurst believes that the susceptibility to insecticides depends partially on the cuticular permeability, but more fundamentally on the effects on internal tissue receptors which control oxidative metabolism or oxidative enzyme systems. The access of pyrethrins to insects, for example, is facilitated by adsorption and storage in the lipophilic layers of the epicuticle. The epicuticle is to be regarded as a lipoprotein mosaic consisting of alternating patches of lipid and protein receptors which are sites of oxidase activity. Such a condition exists in both the hydrophilic type of cuticle found in larvae of Calliphora and Phormia and in the waxy cuticle of Tenebrio larvae. Hurst explains pyrethrinization as a preliminary narcosis or knockdown phase in which oxidase action is blocked by adsorption of the insecticide on the lipoprotein tissue components, followed by death when further dispersant action of the insecticide results in an irreversible increase in the phenoloxidase activity as a result of the displacement of protective lipids. This increase in phenoloxidase activity is accompanied by the accumulation of toxic quinoid metabolites in the blood and tissues—for example, O-quinones which would block substrate access to normal enzyme systems. The varying degrees of susceptibility shown by different insect species to an insecticide may be explainable not only in terms of differences in cuticle make-up but also as internal factors associated with the stability of oxidase systems. 

Equations 27 and 29 are very much like Equations 32 and 33, suggesting that perturbation of the oxidative enzyme systems may be responsible for growth inhibition of the bacteria. 

Of the Phase I reactions, oxidative biotransformations are by far the most common. These reactions are carried out by several oxidative enzyme systems, the most predominant of which is the CYP superfamily of enzymes. Additional oxidative enzymes include FMO, xanthine oxidase, aldehyde oxidase, alcohol and aldehyde dehydrogenases monoamine oxidases, and various peroxidases. Determining the enzyme(s) employed to biotransform any particular substrate will depend on the substrates chemical and physical characteristics as well as functional substituents. This chapter does not describe in detail the mechanism of these various enzymes however, it does illustrate the product(s) (i.e., metabolites) produced by each reaction. 

Eliminations of hydrogen and a halogen occur sometimes during the metabolism of halogenated xenobiotics and lead to an alkene. The double bond may be oxidized into an epoxide by means of oxidative enzyme systems as discussed above. Dehydrogenation, dehydrochlorination and dechlorination are (with oxidation) the different metabolic pathways of the -isomer of the insecticide hexachloro-cyclohexane (lindane). ... 

G Renger and W Weiss (1986) Studies on the nature of the water-oxidizing enzyme. III. Spectral characterization of the intermediary redox states in the water oxidizing enzyme system Y. Biochim Biophys Acta 850 184-196... 

Lu W-P, Kelly DP (1988b) Respiration-driven proton translocation in Thiobacillus versutus and the role of the periplasmic thiosulphate-oxidizing enzyme system. Arch Microbiol 149 297-302... 

The biological action of azides is caused by HN, formed by hydrolysis (Bradbury et al.. 1957 Parochetti and Warren, 1970). The biochemical mode of action is based, according to Keilin (1936), on the paralysis of cell respiration and on the inhibition of the oxidative enzyme system of the cell. 

The lethal oral dose in domestic animals ranges from 1 to 25 mg kg (sodium arsenite), which is three- to ten-fold more toxic than arsenic trioxide. Arsenic affects tissues that are rich in oxidative enzyme systems, and is a capillary poison, resulting in hypovolemia, shock, and circulatory failure. Symptoms of inorganic arsenic poisoning are usually explosive in onset, with intense abdominal pain, vomiting, diarrhea, weakness, staggering gait, hypothermia, and... 

It has been shown that liver slices from mammals contain an oxidative enzyme system capable of converting the P=S linkage to P=0 [40,41]. This enzyme activity has been demonstrated also to exist in the body wall of the locust [42, 43] and in the ganglia of the cockroach [44]. In mammalian liver homogenates, the enzyme system was found to be dependent on Mg +, NAD and nicotinamide [31], while O Brien [45] reported NADPt to be a more efficient cofactor than NAD. 

Table 1. Different fatty acid p-oxidation enzyme systems ... 

Kertesz D (1954) The Phenol Oxidizing Enzyme System of Human Melanomas Substrate Specificity and Relationship to Copper. J Nat Cancer Inst 14 1081... 

Ethanol Ethanol (OES 1000 ppm 8h TWA) has well-known effects on the CNS and can cause irritation. Although metabolised to acetaldehyde and acetate, ethanol appears to have little ability to cause chronic toxic effects at exposure levels likely to be encountered in reasonable industrial and laboratory use. It should be noted that ethanol may compete with other substances present in the workplace atmosphere for the oxidative enzyme systems involved in this metabolism, thereby inhibiting their metabolism or excretion and increasing their toxic effects. This may occur with a number of solvents including trichloroethylene, xylene, benzene and dimethylformamide. The presence of denaturants (e.g. methanol, pyridines) greatly increases the toxicity of ethanol by ingestion and may also present a hazard by the inhalation route. 

Direct measurement of peroxisomal fatty acid oxidation has shown that particularly hydrogenated fish oil and hydrogenated rapeseed oil increased the activity of the peroxisomal P-oxidation enzyme system [7]. 

Labow RS, Meek E, Santerre IP. The biodegradation of poly(urethane)s by the estero-lytic activity of serine proteases and oxidative enzyme systems. 1 Biomater Sci Polym Ed 1999 10(7) 699-713. 

Both the microsomal ethanol oxidizing enzyme system and catalase activities were detected as early as 10 weeks of fetal age, and by contrast to alcohol dehydrogenase, no increases in activity were found during development. Cytochrome P-450 was detected at 13 weeks (Table III), and reached adult levels (Alvares et al., 1969) at 17 weeks of age. The activities of aniline hydroxylase obtained in four fetal livers were comparable to those reported in adult livers (Darby, 1970). The significant activities... 

Flavin Coenzymes, Although many flavin derivatives have been suspected of functioning in oxidizing enzymic systems as prosthetic groups, only two—riboflavin 5-phosphate (flavin mononucleotide, FMN) and flavinade-nine dinucleotide—have been definitely established in enzymic systems. Riboflavin 5 -phosphate (FMN) was identified by Warburg and Christian m ) as a constituent of the old yellow enzyme and its structure elucidated by several workers in different laboratories. Riboflavin, also known as vitamin B2 or lactoflavin, has been synthesized by the following procedure which establishes its structure (147) ... 

In milk, as in many odier foods, oxidative reactions are a prime cause of flavor deterioration and loss in nutritional quality (1). Spontaneous oxidation in milk giving rise to oxidized flavor (off-flavor) is a well-described phenomenon (2 3), i diich is supposed to proceed dependii on factors inherent in die milk itself. These inherent factors include fatty acid conq>osition, content of low-molecular weight antioxidants, pro- and anti-oxidative enzyme systems, and transition metal ion content. Moreover, external factors such as handling, agitation, tenq>erature, exposure to light, and contamination by metals and microorganisms are known to trigger additional deteriorative oxidative reactions in milk. 

The content of the tryptophan-oxidizing enzyme system present in liver commonly is low. It can be increased as much as tenfold through the prior feeding of tryptophan by a mechanism resembling that of enzyme adaptation observed in microorganisms. A much smaller response (twofold) is obtained with certain other substances not substrates of the enzyme system, e.g., epinephrine and histamine. This latter group of compounds has no effect in adrenalectomized animals, and thus, it appears, the increase is caused through a stimulation by the pituitary-adrenal system. ... 

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