Glyoxylate inhibition

Previously we showed (Howitz, McCarty, 1983) that D,L-glycerate and glyoxylate inhibited glycolate uptake, whereas phosphate, acetate and bicarbonate had little effect. A number of other compounds have been tested as potential inhibitors of glycolate accumulation (Table 2). 

Other model reactants are simple organic molecules, for example, formic acid [381, 382]. Pt(lll) exerts lower catalytic influence on HCOOH oxidation than do Pt(lOO) and Pt(llO) faces. However, in the presence of Pb adatoms on Pt(lll) a strong catalytic influence has been observed [383]. The poisonous species production in HCOOH oxidation is then inhibited. Electrochemical reduction of CO2 to glycolate/glyoxylate and oxalic acid has been studied [384]. Other products such as formic acid accompanied by CO and methane have also been detected [385]. In the latter case, the efficiency of the competing process of hydrogen evolution has been suppressed to less than 3.5%. 

Some bacteria, including E. coli, have the full complement of enzymes for the glyoxylate and citric acid cycles in the cytosol and can therefore grow on acetate as their sole source of carbon and energy. The phosphoprotein phosphatase that activates isocitrate dehydrogenase is stimulated by intermediates of the citric acid cycle and glycolysis and by indicators of reduced cellular energy supply (Fig. 16-23). The same metabolites inhibit the protein kinase activity of the bifunctional polypeptide. Thus, the accumulation of intermediates of... 

The same intermediates of glycolysis and the citric acid cycle that activate isocitrate dehydrogenase are allosteric inhibitors of isocitrate lyase. When energy-yielding metabolism is sufficiently fast to keep the concentrations of glycolytic and citric acid cycle intermediates low, isocitrate dehydrogenase is inactivated, the inhibition of isocitrate lyase is relieved, and isocitrate flows into the glyoxylate pathway, to be used in the biosynthesis of carbohydrates, amino acids, and other cellular components. 

Many aroma compounds in fruits and plant materials are derived from lipid metabolism. Fatty acid biosynthesis and degradation and their connections with glycolysis, gluconeogenesis, TCA cycle, glyoxylate cycle and terpene metabolism have been described by Lynen (2) and Stumpf ( ). During fatty acid biosynthesis in the cytoplasm acetyl-CoA is transformed into malonyl-CoA. The de novo synthesis of palmitic acid by palmitoyl-ACP synthetase involves the sequential addition of C2-units by a series of reactions which have been well characterized. Palmitoyl-ACP is transformed into stearoyl-ACP and oleoyl-CoA in chloroplasts and plastides. During B-oxi-dation in mitochondria and microsomes the fatty acids are bound to CoASH. The B-oxidation pathway shows a similar reaction sequence compared to that of de novo synthesis. B-Oxidation and de novo synthesis possess differences in activation, coenzymes, enzymes and the intermediates (SM+)-3-hydroxyacyl-S-CoA (B-oxidation) and (R)-(-)-3-hydroxyacyl-ACP (de novo synthesis). The key enzyme for de novo synthesis (acetyl-CoA carboxylase) is inhibited by palmitoyl-S-CoA and plays an important role in fatty acid metabolism. 

Lawyer, A.L. and I. Zelitch Inhibition of glutamate Glyoxylate aminotransferase activity in tobacco leaves and callus by glycidate, an inhibitor of photorespiration Plant Physiol. 61 (1978) 242-247. 

Kinetic data are available for many aminotransferases, though in most cases the enzyme preparations have consisted either of crude extracts or incompletely purified proteins. Examples of such data are shown in Table 1. The An, value for the keto acid substrate is usually lower than the for the amino acid substrate, but there are exceptions to this generalization. Observed An, values may depend on the conditions of assay, and especially on the ionic composition of the buffer employed. For animal enzymes the anionic components of the buffer are said to be of particular importance in affecting kinetic parameters (cf. Braunstein, 1973). Plant enzymes have not been very systematically investigated in this respect, but phosphate inhibition has been observed for a peroxisomal enzyme transaminating with glyoxylate (Rehfeld and Tolbert, 1972). 

Amination of aldehydes by an amino acid aldehyde aminotransferase from Mercurialis perennis was inhibited strongly by pyruvate, oxaloacetate, and oxoglutarate, and this inhibition was suspected to be competitive (Hartmann et al., 1972). Formation of coniceine by an alanine 5-keto-octanal aminotransferase was inhibited competitively by pyruvate and uncompetitively by glyoxylate (Roberts, 1978). With the L-ornithine 2-oxoacid aminotransferase from Cucurbita pepo, severe inhibition by valine, leucine, and isoleucine could be observed, but there was no inhibition by lysine or proline (Lu and Mazelis, 1975). Cucurbita maxima ornithine aminotransferase, however, was reported to be inhibited by proline (Splittstoesser and Fowden, 1973), as well as by canavanine and diaminobutyrate. 

Application of this inhibitor to pea leaves (Miflin et al., 1966) caused glycine, but not glycolate to accumulate. Also, addition of nonradioactive glyoxylate with radioactive glycine stimulated rather than inhibited radioactive serine formation. It was suggested by Miflin et al. (1966), therefore that serine was formed from two molecules of glycine by a mechanism similar to that already known in bacteria and in avian liver [Eq. (4)]. 

Ozaki, H. and Shiio, I. (1968) Regulation of the TCA and glyoxylate cycles in Brevibacterium jlavum. I. Inhibition of isocitrate lyase and isocitrate dehydrogenase by organic acids related to the TCA and glyoxylate cycles. 

Shiio, I. and Ozaki, H. (1968) Concerted inhibition of isocitrate dehydrogenase by glyoxylate plus oxalacetate. 

A feature of both systems is the autocatalysis by SO4 and COa (derived from the reductant) radicals. A simple rate law is observed in the Ag -catalysed oxidation of aspartic acid (Rate = A a[S208 ][Ag ][Asp] ). Medium effects are important with inhibition by ions in the order Mg + > K+ > Na+ > H+ and NOs > S04 . The uncatalysed oxidations of glyoxal and glyoxylic acid have also been investigated. Potassium ruthenate (K2RUO4), which can be readily prepared from reaction of ruthenium trichloride with aqueous persulphate, can be used cata-lytically in the presence of 8208 for the oxidation of organic substrates under mild conditions. RuO " is considered to act as a two-electron oxidant. 

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