Oxidative Metabolism Catabolism

2 Reactions of Oxidation-Reduction Type 3.2.1 Oxidative Metabolism (Catabolism) 

We can remove electrons from an atom or molecule. Removal of electron in the chemical reaction is defined as oxidation. For an oxidation to occur, there must be an acceptor of the electron(s). Accepting electron(s) is reduction. Oxidation and reduction thus happen simultaneously. In order to see how and where electrons move in chemical reactions, it is convenient to define oxidation state of an atom in a molecule or compound. 

In Other words, the efficiency of energy conversion in the mitochondria is 70%, more than two thirds, which is very good. 

In another process similar to citric acid cycle, NADPH is produced instead of NADH. NADPH is nsed not to produce ATPs but to reduce some important biocompounds, such as sulfate and nitrate, and ribonucleotides (to produce the raw material of DNA) and produce some important biological compounds such as lipids. 

Proteins and lipids are also degraded and partially used to make ATP. A Upid, for example, fatty acid CHjCH CH CH CH CH CH CH CH COOH, has the carbons in low oxidation state [try to calculate it -16/10]. So when it is oxidized, it will give off more energy (per carbon atom) than carbohydrates. That is why fat gives more calories. 

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Further work at EniTecnologies was conducted with Rhodococcus strains. Rhodococ-cus was selected for its metabolical versatility, easy availability in soils and water, and remarkable solvent tolerance. Its capabilities for catalyzing diverse transformation reactions of crude oils, such as sulfur removal, alkanes and aromatics oxidation and catabolism caught their attention. Hence, genetic tools for the engineering of Rhodococcus strains have been applied to improve its biotransformation performance and its tolerance to certain common contaminants of the crude oil, such as cadmium. The development of active biomolecules led to the isolation and characterization of plasmid vectors and promoters. Strains have been constructed in which the careful over-expression of selected components of the desulfurization pathway leads to the enhancement of the sulfur removal activity in model systems. Rhodococcus, Gordona, and Nocardia were transformed in this way trying to improve their catalytic performance in BDS. In a... 

NA NA 45h 60h (second dose) 9mg/m can be given a 2nd dose 14 d later for a total of two doses Exhibit mortality 2 mg/kg ( 1.3x higher than recommended dose) in rats 4.5 mg/kg ( 6x higher than recommended dose) in male monkeys Liver oxidative metabolism of oxogamicin and antibody catabolism... 

Some catabolic reactions depend upon ADP, but under most conditions its concentration is very low because it is nearly all phosphorylated to ATP. Reactions utilizing ADP may then become the rate-limiting pacemakers in reaction sequences. Depletion of a reactant sometimes has the effect of changing the whole pattern of metabolism. Thus, if oxygen is unavailable to a yeast, the reduced coenzyme NADH accumulates and reduces pyruvate to ethanol plus C02 (Fig. 10-3). The result is a shift from oxidative metabolism to fermentation. 

Regulates growth, differentiation, oxidative metabolism, electrolytic balance Increases carbohydrate metabolism, calorigenesis, protein anabolism, ba.sal metabolic rate, oxygen consumption, fat catabolism, fertility Sensitizes nervous system... 

Although catabolism of histidine is not a major source of substituted folate, the reaction is of interest because it has been exploited as a means of assessing folate nutritional stams. In folate deficiency, the activity of the formimi-notransferase is impaired by lack of cofactor. After a loading dose of histidine, there is impaired oxidative metabolism of histidine and accumulation of FIGLU, which is excreted in the urine (Section 10.10.4). 

The second metabolic pathway which we have chosen to describe is the tricarboxylic acid cycle, often referred to as the Krebs cycle. This represents the biochemical hub of intermediary metabolism, not only in the oxidative catabolism of carbohydrates, lipids, and amino acids in aerobic eukaryotes and prokaryotes, but also as a source of numerous biosynthetic precursors. Pyruvate, formed in the cytosol by glycolysis, is transported into the matrix of the mitochondria where it is converted to acetyl CoA by the multi-enzyme complex, pyruvate dehydrogenase. Acetyl CoA is also produced by the mitochondrial S-oxidation of fatty acids and by the oxidative metabolism of a number of amino acids. The first reaction of the cycle (Figure 5.12) involves the condensation of acetyl Co and oxaloacetate to form citrate (1), a Claisen ester condensation. Citrate is then converted to the more easily oxidised secondary alcohol, isocitrate (2), by the iron-sulfur centre of the enzyme aconitase (described in Chapter 13). This reaction involves successive dehydration of citrate, producing enzyme-bound cis-aconitate, followed by rehydration, to give isocitrate. In this reaction, the enzyme distinguishes between the two external carboxyl groups... 

The tricarboxylic acid cycle plays a key role, in centralising the oxidative metabolism of intermediates from catabolic pathways. However, the tricarboxylic acid cycle not only enables the oxidation of acetyl CoA but it also supplies a number of molecules which are used in biosynthetic pathways. Figure 5.13 shows the positions at which... 

This mitochondrial reaction permits the final steps in the catabolism of the branched-chain amino acid leucine. The final products, acetoacetate and acetyl CoA, either are oxidative metabolized to carbon dioxide and water or enter other reactions in lipid metabolism. 

Unlike metabolism in a reducing world, oxidizing metabolism must build biomatter from substrates of lower free energy anabolism and catabolism are opposed. Thus, only in the presence of a non-equilibrium photon spectrum is oxidizing metabolism a relaxation process. 

MCM plays an essential role in propionate metabolism. Propionate and propionyl-CoA are intermediates in the catabolism of leucine and isoleucine and are further metabolized by carboxylation of propionyl-CoA to methylmalonyl-CoA. Isomerization to succinyl-CoA feeds the carbon chain into the tricarboxylic acid pathway of oxidative metabolism. For this reason, MCM is an important enzyme in bacterial and mammalian metabolism. It is one of the two vitamin Bj2-dependent enzymes known to be important in human metabolism. 

The CYPs are present in the liver the greatest concentration is in the smooth endoplasmic reticulum of the centrilobular hepatocytes. They are also present in many other tissues, including the gastrointestinal tract. CYPs are capable of reacting with multiple endogenous and exogenous compounds, and they are active in bilirubin metabolism, cholesterol synthesis, hormone synthesis and catabolism, and vitamin D metabolism. They are of particular interest because of their role in the oxidative metabolism of xenobiotics as part of phase I reactions and the biotransformation of lipophilic compounds to more polar compounds, which are readily excreted by the kidney into the urine. 

ThDP plays a crucial role as coenzyme for several enzymes and enzyme complexes such as transketolase (EC 2.2.1.1) and the enzyme complexes pyruvate (EC 1.2.4.1) and 2-oxoglutarate (EC 1.2.4.2) dehydrogenases, present in nearly all organisms. They play important catabolic roles and are key actors in cell energy metabolism (Figure 5.1). Reduced activity of these enzymes as a consequence of thiamin deficiency results in decreased glucose oxidation. As the brain heavily relies on oxidative metabolism, it is more severely affected by thiamin deficiency than other organs. 

Calculations from the data indicated that oxidative metabolism produced heat of I pW per cell. The Embden-Meyerhof pathway to furnish lactate was estimated to give 1.8 pW per cell. Using an elderly LKB model 10700-1 flow calorimeter (see Reference 28) to pump the cell suspension from a stirred vessel, the heat production was found to be 2.5 pW per cell. Compared to the calculated value of 2.8 pW per cell, the similarity was considered to be within the experimental error to justify that all the catabolic pathways had been held to account for the respiratory burst. 

Fig. 7. Model for the subcellular localization of reactions of purine synthesis and ureide biogenesis in nodules of ureide-exportlng legumes. The model is based on results of subcellular fractionation and ultrastructural studies. The processes (shown in the hatched boxes) involved in ureide biogenesis (i.e., nitrogen fixation, ammonium assimilation, precursor synthesis, purine synthesis, energy-yielding metabolism, and purine oxidation and catabolism) may occur in more than one subcellular compartment. The location of the enzymes involved in the conversion of IMP to xanthine is not certain. We have proposed that in soybean nodules these reactions [shown in bold-face type with bold arrows] occur in the plastid while in other species such as cowpea these reactions may take place in the ground cytoplasm. In all cases the intermediate exported from the plastid is uncertain. This uncertainty is indicated with the dashed lines and question marks.

The combustion of the acetyl groups of acetyl-CoA by the citric acid cycle and oxidative phosphorylation to produce COg and HgO represents stage 3 of catabolism. The end products of the citric acid cycle, COg and HgO, are the ultimate waste products of aerobic catabolism. As we shall see in Chapter 20, the oxidation of acetyl-CoA during stage 3 metabolism generates most of the energy produced by the cell. 

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