Succinate decarboxylase

Kohler, P., Bryant, C. and Behm, C.A. (1 978) ATP synthesis in a succinate decarboxylase system from Fasciola hepatica mitochondria. International Journal for Parasitology 8, 399 104. 

Fig. 5.4. Two types of energy metabolism in cestodes. (a) Type 1 homolactate fermentation, (b) Type 2 Malate dismutation. Reaction 3 involves a carboxylation step decarboxylation occurs at 6, 7 and 10. Reducing equivalents are generated at reactions 6 and 7 one reducing equivalent is used at reaction 9. Thus, when the mitochondrial compartment is in redox balance and malate is the sole substrate, twice as much propionate as acetate is produced. Key 1, pyruvate kinase 2, lactate dehydrogenase 3, phosphoenolpyruvate carboxykinase 4, malate dehydrogenase 5, mitochondrial membrane 6 malic enzyme 7, pyruvate dehydrogenase complex 8, fumarase 9, fumarate reductase 10, succinate decarboxylase complex. indicates reactions at which ATP is synthesised from ADP cyt, cytosol mit, mitochondrion. (After Bryant Flockhart, 1986.)...

Fumarate acts as substrate for an important enzyme complex, fumarate reductase, which occurs in a number of cestodes (698). Fumarate reductase accepts reducing equivalents (NADH or NADPH), generated by malic enzyme, and transfers the electrons to fumarate, which is thus reduced to succinate. The reduction of fumarate to succinate is accompanied by the phosphorylation of ADP, one ATP being produced for each fumarate reduced. This phosphorylation involves the cytochrome chain. Succinate may be excreted or is converted by another enzyme complex, succinate decarboxylase, to propionate and excreted. 

Tissues of the mammalian central nervous system contain a pyridoxal phosphate-dependent glutamate decarboxylase that catalyzes conversion of Glu to y-aminobutyrate (GABA), an inhibitory synaptic transmitter. GABA is degraded by trans-imination with a-oxoglutarate as the acceptor to yield succinic semialdehyde, which then is oxidized to succinate by an NAD-linked dehydrogenase. 

Figure 6.3. GABA shunt as an alternative to a-ketoglutarate dehydrogenase in the citric acid cycle. 2-Oxoglutarate dehydrogenase, EC 1.2.4.2 glutamate decarboxylase, EC 4.1.1.15 GABA aminotransferase, EC 2.6.1.19 and succinic semialdehyde dehydrogenase, ECl.2.1.16.

Figure 12-4. Gamma-aminobutyric acid metabolic interactions. GA = glutaminase GABA = y-aminobutyric acid GABA-T = GABA a-oxaloglutarate transaminase GAD = glutamic acid decarboxylase GS = glutamic synthetase NAD+ = nicotinamide adenine dinucleotide PP = pyridoxal phosphate (vitamin B6) SSA = succinic semialdehyde SSADH = succinic semialdehyde dehydrogenase GHB = y-hydroxybutyric acid GBL = y-butyrolactone.

FIG. 4.2 Malate metabolism in mitochondria from body wall muscle of adult Ascaris smm. (1) Fumarase (2) malic enzyme (3) pyruvate dehydrogenase complex (4) complex I (5) succinate-coenzyme Q reductase (complex II, fumarate reductase) (6) acyl CoA transferase (7) methylmalonyl CoA mutase (8) methyl-malonyl CoA decarboxylase (9) propionyl CoA condensing enzyme (10) 2-methyl acetoacetyl CoA reductase (11) 2-methyl-3-oxo-acyl CoA hydratase (12) electron-transfer flavoprotein (13) 2-methyl branched-chain enoyl CoA reductase (14) acyl CoA transferase. 

NO has a cytostatic effect by inhibiting ATP synthesis [99] via Kreb s cycle (aconitase inhibition, [100]), glycolysis (GADPH inhibition) and mitochondrial respiration (NAD ubiquinone oxydoreductase and succinate ubiquinone oxydoreductase inhibitions, [101]). Another pathway is the ornithine decarboxylase inhibition. This enzyme is implicated in polyamine production necessary to cell proliferation and its activity is inhibited by NO in human colon cancer cells HT-29 and Caco-2 [102]. Furthermore NO directly inactivates ribonucleotide reductase [103] of TA3 cancer cells (murine breast cancer cells) [104]. This enzyme controlling DNA synthesis catalyses desoxyribonucleotides synthesis, and its inhibition blocks cells in S phase. This inhibition is rapid and reversible in K562 and TA3 cells [105]. 

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