Cleavage, oxidative mechanisms

Carotenoid oxidation products are also supposed to have detrimental effects in vivo. As mentioned earlier, they are suspected to be involved in the adverse effects of high doses of 3-carotene supplementation in smokers and asbestos workers (CARET and ATBC studies) and in smoke-exposed ferrets. The mechanisms potentially involved have been investigated in vitro. P-Apo-8 -carotenal, an eccennic cleavage oxidation product of P-carotene, was shown to be a strong inducer of CYPlAl in rats, whereas P-carotene was not active. Cytochrome P450 (CYP 450) enzymes thus induced could enhance the activation of carcinogens and the destruction of retinoic acid. ... 

Ketones are oxidatively cleaved by Cr(VI) or Mn(VII) reagents. The reaction is sometimes of utility in the synthesis of difunctional molecules by ring cleavage. The mechanism for both reagents is believed to involve an enol intermediate.206 A study involving both kinetic data and quantitative product studies has permitted a fairly complete description of the Cr(VI) oxidation of benzyl phenyl ketone.207 The products include both oxidative-cleavage products and benzil, 7, which results from oxidation a to the carbonyl. In addition, the dimeric product 8, which is suggestive of radical intermediates, is formed under some conditions. 

Oxidation of higher fatty acids was first studied in 1904 by Knoop who fed animals with phenyl-substituted fatty acids and analyzed the products in the urine. He showed that the fatty acid oxidation results in the successive cleavage of two carbon moieties from the carboxyl end. Knoop coined the fatty acid oxidation mechanism as n-oxidation. As has been established by Kennedy and Lehninger in 1948-1949, oxidation of fatty acids occurs in the mitochondria only. Lynen and coworkers... 

Since carbon-halogen bond cleavage is not a favorable process, and since both carbon and oxygen atoms have an even number of electrons, the oxidation proceeds either via free radicals or via carbenes and triplets. As a result, the oxidation mechanisms are considerably simpler than with hydrocarbons. Section III of this review treats free radical oxidation, whereas Section IV treats oxidation by processes not involving free radicals. In this discussion a free radical is considered to be a species with an odd number of electrons carbenes and triplets are called biradicals and are not included in this category. 

Photodegradation. UV/Vis exposure can induce protein oxidation, aggregation, and backbone cleavage. For example, oxidation has been observed in the histidine residue of human growth hormone (hGH) exposed to photostability conditions (6.7 x 106 lux hours). The proposed oxidation mechanism and product is shown in Figure 136. 

II. Mechanism of Glycol-cleavage Oxidation by Lead Tetraacetate. 11... 

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