Aerobic oxidative metabolism

Fig. 3.2 Biological abstraction. Yeast cells reflect anaerobic, reductive metabolism (intestine) as well as aerobic, oxidative metabolism (liver), if glycolysis is regarded as the most active pathway. Therefore, the yeast Saccharomyces cerevisiae is a good model organism for studies of xenobiotic metabolism.

To gain further insight into the age-related adaptation of skeletal muscle to a more aerobic-oxidative metabolism, studying mitochondrial bioenergetic parameters and mitochondrial oxidative phosphorylation efficiency is of crucial importance. 

Glucose is metabolized to pyruvate by the pathway of glycolysis, which can occur anaerobically (in the absence of oxygen), when the end product is lactate. Aerobic tissues metabolize pyruvate to acetyl-CoA, which can enter the citric acid cycle for complete oxidation to CO2 and HjO, linked to the formation of ATP in the process of oxidative phosphorylation (Figure 16-2). Glucose is the major fuel of most tissues. 

The citric acid cycle is the final common pathway for the aerobic oxidation of carbohydrate, lipid, and protein because glucose, fatty acids, and most amino acids are metabolized to acetyl-CoA or intermediates of the cycle. It also has a central role in gluconeogenesis, lipogenesis, and interconversion of amino acids. Many of these processes occur in most tissues, but the hver is the only tissue in which all occur to a significant extent. The repercussions are therefore profound when, for example, large numbers of hepatic cells are damaged as in acute hepatitis or replaced by connective tissue (as in cirrhosis). Very few, if any, genetic abnormalities of citric acid cycle enzymes have been reported such ab-normahties would be incompatible with life or normal development. 

The major biochemical features of neutrophils are summarized in Table 52-8. Prominent feamres are active aerobic glycolysis, active pentose phosphate pathway, moderately active oxidative phosphorylation (because mitochondria are relatively sparse), and a high content of lysosomal enzymes. Many of the enzymes listed in Table 52-4 are also of importance in the oxidative metabolism of neutrophils (see below). Table 52-9 summarizes the functions of some proteins that are relatively unique to neutrophils. 

In some cases, microorganisms can transform a contaminant, but they are not able to use this compound as a source of energy or carbon. This biotransformation is often called co-metabolism. In co-metabolism, the transformation of the compound is an incidental reaction catalyzed by enzymes, which are involved in the normal microbial metabolism.33 A well-known example of co-metabolism is the degradation of (TCE) by methanotrophic bacteria, a group of bacteria that use methane as their source of carbon and energy. When metabolizing methane, methanotrophs produce the enzyme methane monooxygenase, which catalyzes the oxidation of TCE and other chlorinated aliphatics under aerobic conditions.34 In addition to methane, toluene and phenol have been used as primary substrates to stimulate the aerobic co-metabolism of chlorinated solvents. 

C5a and C5a des Arg stimulate aerobic glycolysis, hexose monophosphate shunt activity, glucose uptake and the respiratory burst of human neutrophils. All of these processes are stimulated in neutrophil suspensions incubated in the absence of cytochalasin B, but the responses are considerably enhanced if this inhibitor of microtubule assembly is present. Stimulated rates of oxidative metabolism are maximal within 2 min of addition of peptides, with half-maximal responses obtained at 30-60 nM C5a and 1-3 pM C5a des Arg. 

TCE is the other major contaminant at the site and is a common groundwater contaminant in aquifers throughout the United States [425]. Since TCE is a suspected carcinogen, the fate and transport of TCE in the environment and its microbial degradation have been extensively studied [25,63, 95,268,426,427]. Reductive dechlorination under anaerobic conditions and aerobic co-metabolic processes are the predominant pathways for TCE transformation. In aerobic co-metabolic processes, oxidation of TCE is catalyzed by the enzymes induced and expressed for the initial oxidation of the growth substrates [25, 63, 268, 426]. Several growth substrates such as methane, propane, butane, phenol, and toluene have been shown to induce oxygenase enzymes which co-metabolize TCE [428]. 

It has now been found that the quinones 13, 14 and 15 from the aerobic oxidation of veratryl alcohol by lignin peroxidase were also reduced by fungal mycelium to yield the corresponding hydroquinones. For quinone 14 this reduction had already been reported by Buswell et al. (17) in a study of vanillic acid metabolism. 

In eukaryotes, most of the reactions of aerobic energy metabolism occur in mitochondria. An inner membrane separates the mitochondrion into two spaces the internal matrix space and the intermembrane space. An electron-transport system in the inner membrane oxidizes NADH and succinate at the expense of 02, generating ATP in the process. The operation of the respiratory chain and its coupling to ATP synthesis can be summarized as follows ... 

The aerobic pathway via the Krebs cycle yields 36 moles of ATP, while the anaerobic process utilizing glycolysis yields only 2-3 moles. Clearly, fish performing work of great capacity must cultivate oxidative metabolism... 

Aerobic hydrocarbon metabolism has been well studied and reviewed by an number of authors (1-6L Two general pathways are shown in Figures 1 and 2. The initial oxidation of alkanes commonly occurs on the terminal carbon yielding an alcohol (Figure 1). This is further oxidized to an aldehyde and then to a carboxylic acid which undergoes a series of (5-oxidations. Each p-oxidation yields acetic acid and a carboxylic acid with two fewer carbon atoms than the previous acid. 

Figure 1. Intermediates in the aerobic microbial metabolism of n-alkanes by a terminal oxidation and subsequent p-oxidations.

Benzothiophene. There have been several reports on the aerobic co-metabolism of benzothiophene (42, 46, 47). Bohonos et al. (46) identifed some benzothiophene metabolites by GC-MS and the structures of these are shown in Figure 8. Although the only compounds found were oxidized on the thiophene ring, they could not exclude the possibility of oxidation of the benzene ring. Finnerty et al. (48) found that benzothiophene was transformed to unidentified water-soluble products by a dibenzothiophene-oxidizing bacterium. 

Since mitochondria are the site of high oxidative metabolism, they are under continual oxidative stress. In fact, it has been estimated that approximately 2 percent of mitochondrial 02 consumption generates ROS. The mitochondrial electron transfer chain is one of the main sources of ROS in aerobic cells, due to electron leakage from energy-transducing sequences leading to the formation of superoxide radicals. 

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