Succinate accumulation

It has been suggested by Podesta et al. (650) that ambient C02 levels determine the amount of succinate and lactate excreted by intestinal helminths. A summary of the events which they propose lead to succinate accumulation in H. diminuta is provided in Fig. 5.7. There is considerable release of C02 in the post-prandial intestine of the rat host as the acidic chyme is passed into the duodenum and there is an acidification of worm tissues as the C02 diffuses in. The acidification is countered by worm secretion of H+ and by mobilisation of Ca2 + from the calcareous corpuscles (Chapter 4), thus releasing carbonate. The increased osmolality and greater HC03 concentration activate PEPCK, which favours succinate production over lactate. Succinate, being a dicarboxylic acid, is twice as effective as lactate in metabolic disposal of H+. With a decrease in passage of stomach chyme into the intestine, there would be a decrease in acid stress on the worms, accompanied by a concomitant decrease in tissue HC03 concentrations and osmolality, which would favour lactate production. 

Fig. 5.7. Summary of events leading to succinate accumulating in Hymenolepis diminuta. 1, Tissue acidification by ambient C02 2, H+ secretion. 3, Tonicity of fluid absorbed by the worm. 4, Ca2+ secretion. 5, Metabolic consequences of tissue buffering problem. (After Podesta et al., 1976.)...

Fig. 5.9. Proposed scheme for the intramitochondrial metabolism of malate by Hymenolepis diminuta. Abbreviations ME, malic enzyme F, fumarase T, transhydrogenase FR, fumarate reductase ETS, electron transport system. Once within the matrix compartment, malate oxidation, as catalysed by malic enzyme, results in NADPH formation. Via the activity of fumarase, malate also is converted to fumarate in the matrix compartment. NADPH then serves as a substrate for the inner-membrane-associated transhydrogenase and transhydrogenation between NADPH and matrix NAD is a scalar reaction associated with the matrix side of the inner membrane. Matrix NADH so formed reduces the electron transport system via a site on the matrix side of the inner membrane permitting fumarate reductase activity. The reduction of fumarate to succinate results in succinate accumulation within the matrix compartment. (After McKelvey Fioravanti, 1985.)...

In yeast grown under hypoxic conditions succinate accumulates and the Krebs cycle is split in two branches, one diverging from oxaloacetate to succinate with simultaneous NAD recovery and the other one from oxaloacetate to glutamate, in which the NADP-linked isocitrate dehydrogenase produces the substrates needed for the NADP-linked glutamate dehydrogenase, namely 2-oxoglutarate and NADPH.< )... 

In a 2-1. round-bottomed, 3-necked flask fitted with a stirrer and two large-bore condensers are placed 200 cc. of 50 per cent nitric acid and 0.25 g. of vanadium pentoxide. The flask is heated to 65-70° in a water bath (thermometer in water), and I cc. of cyclopentanone added. Oxidation is indicated by the production of brown fumes. The water bath is removed, and 42 g. (less the i cc.) of the cyclic ketone added from a dropping funnel through the condenser at the rate of a drop every three seconds. The heat of the reaction keeps the flask at about 70°. If the temperature drops, oxidation ceases until the ketone has accumulated, when it may proceed almost explosively. In such a case, or if the temperature is higher, much succinic acid is formed. After addition has been completed, the water bath... 

Different organic acids, primarily lactic acid, have been successfully used for decontamination of whole livestock carcasses, and the application of different organic acids used for decontamination has also been tested in the fruit and vegetable industry. Organic acids other than lactic acid that are known to have bactericidal effects are acetic, benzoic, citric, malic, propanoic, sorbic, succinic and tartaric acids (Betts and Everis 2005). The antimicrobial action is due to a reduction in the pH in the bacterial environment, disruption of membrane transport, anion accumulation or a reduction in the internal pH in the cell (Busta et al., 2001). Many fruits contain naturally occurring organic acids. Nevertheless, some strains, for example E. coli 0157, are adapted to an acidic environment. Its survival, in combination with its low infective dose, makes it a health hazard for humans. 

Oxidizible substrates from glycolysis, fatty acid or protein catabolism enter the mitochondrion in the form of acetyl-CoA, or as other intermediaries of the Krebs cycle, which resides within the mitochondrial matrix. Reducing equivalents in the form of NADH and FADH pass electrons to complex I (NADH-ubiquinone oxidore-ductase) or complex II (succinate dehydrogenase) of the electron transport chain, respectively. Electrons pass from complex I and II to complex III (ubiquinol-cyto-chrome c oxidoreductase) and then to complex IV (cytochrome c oxidase) which accumulates four electrons and then tetravalently reduces O2 to water. Protons are pumped into the inner membrane space at complexes I, II and IV and then diffuse down their concentration gradient through complex V (FoFi-ATPase), where their potential energy is captured in the form of ATP. In this way, ATP formation is coupled to electron transport and the formation of water, a process termed oxidative phosphorylation (OXPHOS). 

Krebs cycle is inhibited at the points where a-ketoglutarate dehydrogenase and succinate dehydrogenase operate. This causes an increase in organic acids and an accumulation of glutamate. 

In muscle, 90% of all respiration was inhibited and succinate was shown to accumulate, powerful proof of the importance of the citric acid cycle in the respiration of animal tissues. 

Some of the glucose is converted to D-lactic and to succinic acids (pathway/, Fig. 17-9) hence the name mixed acid fermentation. Table 17-1 gives typical yields of the mixed acid fermentation of E. coli. Among the four major products are acetate, ethanol, H2, and C02, as shown in Eq. 17-25. However, at high pH formate accumulated instead of C02. 

Functioning in a somewhat different way in E. coli are 6- to 12-residue periplasmic membrane-derived oligosaccharides. These are p-1,2- and P 1,6-linked glucans covalently linked to sn-l-phospho-glycerol, phosphoethanolamine, or succinate (see Fig. 8-28).b e/f They accumulate in the periplasm when cells are placed in a medium of low osmolarity. 

Further support for the cyclical nature of the chain came from observations of malonate-inhibited muscle slices. In such preparations the addition of any of the intermediates of the chain led to accumulation of succinate. Even the addition of fumarate, the immediate product of succinate oxidation, led to accumulation of succinate. 

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