Succinic acid oxidase

Organic acids are responsible for the acidity of honey and contribute considerably to its unique flavor (Anklam, 1998). Organic acid content of about 0.57% consists primarily of gluconic acid. It is a by-product of the enzymatic action of glucose oxidase on glucose (Olaitan et ah, 2007). Other organic acids identified up to the present are the pyruvic acid, malic acid, citric acid, succinic acid, and fumaric acid. 

Mercury interferes with mitochondrial oxidation in the brain through mercaptide formation with thiol groups in pyruvate oxidase. Succinic dehydrogenase of the citric acid cycle is also inhibited. 

The FAD-requiring enzymes in mammalian systems include the D- and L-amino acid oxidases, mono- and diamine oxidases, glucose oxidase, succinate dehydrogenase, a-glycerophosphate dehydrogenase, and glutathione reductase. FMN is a cofactor for renal L-amino acid oxidase, NADH reductase, and a-hydroxy acid oxidase. In succinate dehydrogenase, FAD is linked to a histidyl residue in liver mitochondrial monoamine oxidase, to a cysteinyl residue. In other cases, the attachment is nonco-valent but the dissociation constant is very low. 

The nucleus is lacking in a number of important enzymes for cellular oxidation such as cytochrome oxidase, succinic dehydrogenase, uricase, D-amino acid oxidase, etc., and so respiration does not occur. However, it does contain a glycolytic system, although of low activity. In the nucleus is concentrated a system of enzymes for the synthesis of nucleic acids and nucleotides. It is found that radioactive phosphorus is always incorporated more rapidly into the RNA of the nucleus than into the RNA of the cytoplasm. So, there is little doubt that the nucleus contains enzyme systems for the synthesis of the two types of nucleic add. 

Keilin and Hartree tested the catalytic effect of the two cytochrome preparations with (1) cytochrome oxidase, cytochrome c, and ascorbic acid, and (2) cytochrome oxidase, cjriochrome c, succinic dehydrogenase, and succinic acid without finding any difference per iron atom in the effect of the two cytochrome preparations. This, in our view, indicates that certain inert impurities (in these two systems) are removed on the final purification, rather than that 20% of the cytochrome molecule is split off in the purification. 

In addition to binding to cytochrome c oxidase, cyanide inhibits catalase, peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, and succinic dehydrogenase activities. These reactions may make contributions to the signs of cyanide toxicity (Ardelt et al. 1989 Rieders 1971). Signs of cyanide intoxication include an initial hyperpnea followed by dyspnea and then convulsions (Rieders 1971 Way 1984). These effects are due to initial stimulation of carotid and aortic bodies and effects on the central nervous system. Death is caused by respiratory collapse resulting from central nervous system toxicity. 

Freebaim noted a decrease in oxygen uptake of plant and bovine liver mitochondria that was reversible by glutathione and ascorbic acid. The activity of some mitochondrial enzymes, including succinic dehydrogenase and cytochrome oxidase, has been found to be susceptible to ozone. 

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). 

Oxidation of a-amino acids to keto acids catalysed by D- and L-amino acid oxidases Oxidation of NADH via the cytochrome system catalyzed by cytochrome reductase Energy production via the TCA or Krebs cycle catalyzed by succinate dehydrogenase Fatty acid oxidation catalyzed by acyl-coenzyme A dehydrogenases Synthesis of fatty acids from acetate (80,81)... 

Figure 7-1. Pathways of fuel metabolism and oxidative phosphorylation. Pyruvate may be reduced to lactate in the cytoplasm or may be transported into the mitochondria for anabolic reactions, such as gluconeogenesis, or for oxidation to acetyl-CoA by the pyruvate dehydrogenase complex (PDC). Long-chain fatty acids are transported into mitochondria, where they undergo [ -oxidation to ketone bodies (liver) or to acetyl-CoA (liver and other tissues). Reducing equivalents (NADH, FADII2) are generated by reactions catalyzed by the PDC and the tricarboxylic acid (TCA) cycle and donate electrons (e ) that enter the respiratory chain at NADH ubiquinone oxidoreductase (Complex 0 or at succinate ubiquinone oxidoreductase (Complex ID- Cytochrome c oxidase (Complex IV) catalyzes the reduction of molecular oxygen to water, and ATP synthase (Complex V) generates ATP fromADP Reprinted with permission from Stacpoole et al. (1997).

Succinate dehydrogenase is the only enzyme of the citric acid cycle which is bound to the inner membrane of mitochondria. It is also one of three flavoproteins known in which flavin is covalently linked to the protein. The other two are monoamine oxidase of the outer membrane of liver mitochondria (138) and Chromatium cytochrome c-552 (139). 

Succinic dehydrogenase Cytochrome oxidase Acid phosphatase Aryl sulfatase Catalase... 

The intermediate EiP, which is the major species of reduced enzyme with which O2 reacts in the amino acid oxidase reaction, is more reactive with O2 than Er in one case (49) (D-amino acid oxidase) but less reactive in the other (18) (n-amino acid oxidase). The reasons for such seemingly inconsistent behavior, as well as the virtual lack of reactivity of reduced flavins with O2 in systems such as succinic dehydrogenase, will only become clear when the molecular details of the oxidation mechanism of reduced flavin are elucidated. 

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