Oxidation in metabolism

The publication (70) in 1976 of the preparation of optically active epoxyketones via asymmetric catalysis marked the start of an increasingly popular field of study. When chalcones were treated with 30% hydrogen peroxide under (basic) phase-transfer conditions and the benzylammonium salt of quinine was used as the phase-transfer catalyst, the epoxyketones were produced with e.e. s up to 55%. Up to that time no optically active chalcone epoxides were known, while the importance of epoxides (arene oxides) in metabolic processes had just been discovered (71). The nonasymmetric reaction itself, known as the Weitz-Scheffer reaction under homogeneous conditions, has been reviewed by Berti (70). 

Upon oxidation in metabolism, lipids yield large amounts of energy. 

Aromatic Ifydroxylation and Alkyl Oxidation in Metabolism of MLto-tane (o,p -DDD) in Humans J. Pharm. Sci. 63(11) 1730-1736 (1974) CA 82 132718t... 

Synthetic estrogens such as 17-ethynylestradiol are birth control agents. Estradiol, the female sex hormone, is a secondary alcohol that cannot be administered orally because it would be rapidly oxidized by the hver. The synthetic estrogens contain an ethynyl group (—C=CH) and are tertiary alcohols that are not oxidized in metabolic reactions. The ethynyl group in these compounds is located so that the hydroxyl group has the same stereochemistry as the natural estradiol. 

The 1,2-shift in the dehydration of rranj-l-hydroxy-2-ethylthio-l,2-dihydro-naphthalene, a simple model for the glutathione-naphthalene 1,2-oxide adduct (the so-called premercapturic acid which is receiving considerable attention because of the importance of arene oxides in metabolism), leads to ethyl 1-naphthyl sulphide via a cyclic sulphonium ion, ... 

A quote from a biochemistry text IS instructive here This IS not an easy reaction in or game chemistry It is how ever a very important type of reaction in metabolic chemistry and is an integral step in the oxidation of car bohydrates fats and several ammo acids G L Zubay Biochemistry 4th ed William C Brown Publishers 1996 p 333... 

Side-chain oxidation of alkylbenzenes is important in certain metabolic processes. One way in which the body rids itself of foreign substances is by oxidation in the liver to compounds that are more polar- and hence more easily excreted in the urine. Toluene, for example, is oxidized to benzoic acid by this process and is eliminated rather readily. 

A -Pyrroline has been prepared in low yield by oxidation of proline with sodium hypochlorite (71), persulfate (102), and periodate (103). A -Pyrroline and A -piperideine are products of enzymic oxidation via deamination of putrescine and cadaverine or ornithine and lysine, respectively (104,105). This process plays an important part in metabolism and in the biosynthesis of various heterocyclic compounds, especially of alkaloids. 

Fatty acids with odd numbers of carbon atoms are rare in mammals, but fairly common in plants and marine organisms. Humans and animals whose diets include these food sources metabolize odd-carbon fatty acids via the /3-oxida-tion pathway. The final product of /3-oxidation in this case is the 3-carbon pro-pionyl-CoA instead of acetyl-CoA. Three specialized enzymes then carry out the reactions that convert propionyl-CoA to succinyl-CoA, a TCA cycle intermediate. (Because propionyl-CoA is a degradation product of methionine, valine, and isoleucine, this sequence of reactions is also important in amino acid catabolism, as we shall see in Chapter 26.) The pathway involves an initial carboxylation at the a-carbon of propionyl-CoA to produce D-methylmalonyl-CoA (Figure 24.19). The reaction is catalyzed by a biotin-dependent enzyme, propionyl-CoA carboxylase. The mechanism involves ATP-driven carboxylation of biotin at Nj, followed by nucleophilic attack by the a-carbanion of propi-onyl-CoA in a stereo-specific manner. 

What would be the consequences of a deficiency in vitamin Bi2 for fatty acid oxidation What metabolic intermediates might accumulate ... 

Ethanol metabolism occurs mainly in the liver and proceeds by oxidation in two steps, first to acetaldehyde (CHjCHO) and then to acetic add (CH3CO2H)- When continuously present in the body, ethanol and acetaldehyde are toxic, leading to the devastating physical and metabolic deterioration... 

Ethanol also inhibits ADH-catalyzed retinol oxidation in vitro, and ethanol treatment of mouse embtyos has been demonstrated to reduce endogenous RA levels. The inhibition of cytosolic RolDH activity and stimulation of microsomal RolDH activity could explain ethanol-mediated vitamin A depletion, separate from ADH isoenzymes. Although the exact mechanism of inhibition of retinoid metabolism by ethanol is unclear, these observations are consistent with the finding that patients with alcoholic liver disease have depletedhepatic vitamin A reserves [review see [2]. 

Many metabolic fuels are oxidized in the mitochondrial matrix. Pyruvate is oxidatively decarboxylated to acetyl-CoA by the pyruvate dehydrogenase complex (PDH)... 

The metabolism of amino acids is complex and is described in standard text books. These are usually converted by aminotransferases to the corresponding 2-oxoacids which are partly oxidized in the matrix of muscle mitochondria and partly exported to the liver. Glutamate and aspartate yield 2-oxoglutarate and oxaloacetate, respectively, which enter the citrate cycle directly, and other 2-... 

Ethanol is oxidized by alcohol dehydrogenase (in the presence of nicotinamide adenine dinucleotide [NAD]) or the microsomal ethanol oxidizing system (MEOS) (in the presence of reduced nicotinamide adenine dinucleotide phosphate [NADPH]). Acetaldehyde, the first product in ethanol oxidation, is metabolized to acetic acid by aldehyde dehydrogenase in the presence of NAD. Acetic acid is broken down through the citric acid cycle to carbon dioxide (CO2) and water (H2O). Impairment of the metabolism of acetaldehyde to acetic acid is the major mechanism of action of disulfiram for the treatment of alcoholism. 

For several hours after a meal, while the products of digestion are being absorbed, there is an abundant supply of metabolic fuels. Under these conditions, glucose is the major fuel for oxidation in most tissues this is observed as an increase in the respiratory quotient (the ratio of carbon dioxide produced to oxygen consumed) from about 0.8 in the starved state to near 1 (Table 27-1). 

Figure 27-1. Metabolic interrelationships between adipose tissue, the liver, and extrahepatic tissues. In extrahepatic tissues such as heart, metabolic fuels are oxidized in the following order of preference (1) ketone bodies, (2) fatty acids, (3) glucose. (LPL, lipoprotein lipase FFA, free fatty acids VLDL, very low density lipoproteins.)...

Table 27-1. Energy yields, oxygen consumption, and carbon dioxide production in the oxidation of metabolic fuels.

The free energy changes in metabolic oxidation reactions serve several purposes. Part of this energy appears as heat flows that maintain body temperature and disperse energy to the surroundings. Another portion of the energy... 

A formally comparable pathway is used by a strain of Alcaligenes sp. that degrades 4-hydroxyacetophenone to 4-hydroxybenzoyl methanol, which is oxidized in an unusual reaction to 4-hydroxybenzoate and formate. The 4-hydroxybenzoate is then metabolized to 3-ketoadipate via 3,4-dihydroxybenzoate (Figure 8.35b) (Hopper et al. 1985). 

Long MT, BA Bartholomew, Ml Smith, PW Trudgill, DJ Hopper (1997) Enzymology of oxidation of tropic acid to phenylacetic acid in metabolism of atropine by Pseudomonas sp. strain AT3. J Bacteriol 179 1044-1050. 

Ziegler, D.M. (1985). Role of reversible oxidation-reduction of enzyme thiol-disulphides in metabolic regulation. Annu. Rev. Biochem. 54, 305-329. 

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