The Functional Significance of the Pentose Phosphate Pathway in Synaptosomes: Protection Against Peroxidative Damage by Catecholamines and Oxidants

Abstract

Catecholamines added in vitro in rat brain synaptosomes activate the decarboxylation of glucose radioactively labelled on carbon 1, suggesting an effective activation of the pentose phosphate pathway. Stimulation also occurred with phenazine methosulphate, reduced glutathione and hydrogen peroxide. The activation of the pentose phosphate pathway by 5-hydroxytryptamine, noradrenaline and dopamine is ascribed to the activation of monoamine oxidase, producing both the respective biogenic aldehyde and hydrogen peroxide. Evidence is presented that the further metabolism of the aldehyde by aldehyde reductase and the removal of hydrogen peroxide by glutathione peroxidase both release the limitation of NADP+ availability for the pentose phosphate pathway by leading to the oxidation of NADPH. The relevance of the maintenance of reduced NADP+ on brain is discussed in relation to the metabolism of glutathione and to lipid peroxidation.

Effect of Sulfur Dioxide on Active and Passive Avoidance in Experimental Diabetes Mellitus: Relation to Oxidant Stress and Antioxidant Enzymes

“…Hydrogen peroxide can be decomposed by CAT and GSH-Px (Shaheen et al, 1996). Earlier studies have reported that H 2 O 2 detoxification was critically dependent on GSH system in the hippocampus, because it can also interact directly with lipid peroxides (Hothersall et al, 1982;Kish et al 1985). The present data showing the reduction of hippocampus GSH-Px activity and unaltered CAT activity following SO 2 exposure are also agreement with this point.…”

Underestimation of the Pentose–Phosphate Pathway in Intact Primary Neurons as Revealed by Metabolic Flux Analysis

“…Thus, the difference between the rates of 14 CO 2 released from [1-14 C]glucose and that from [6-14 C]glucose is considered acceptable to estimate glucose oxidized through the PPP. 11 As shown in Figure 1B, we found that the rate of glucose oxidized through the PPP in neurons was B0.2 nmoL/minute  mg protein. This PPP value is, indeed, lower than the one reported in a previous work, 1 possibly reflecting the drawbacks of using suspended neurons in that study.…”

“…Unfortunately, it was not taken into account that a fraction of [1,[3][4][5][6][7][8][9][10][11][12][13] C]F6P formed from PPP, by conversion into [1,[3][4][5][6][7][8][9][10][11][12][13] C]G6P through PGI, returns [2,[3][4][5][6][7][8][9][10][11][12][13] C]F6P in the second PPP round. Thus, as from the second PPP round and thereafter -up to the 4 hours of incubation-such [2,[3][4][5][6][7][8][9][10][11][12][13] C]F6P will label [1-13 C]acetylCoA hence largely over-estimating glycolysis. 2 We therefore conclude that an important proportion of glucose entering neurons is oxidized through the PPP …”

Causes and consequences of the loss of serotonergic presynapses elicited by the consumption of 3,4-methylenedioxymethamphetamine (MDMA, ?ecstasy?) and its congeners

“…The proponents of this hypothesis have some difficulties to explain the severe loss of 5-HT afferences in areas of low dopaminergic innervation in the rat, such as hippocampus and cortex and the lack of damage observed after intracerebral administration of these drugs. More importantly, this hypothesis completely ignores the fact that serotonergic (like all other) presynapses are endowed with several protective mechanisms which are very effective in the prevention or repair of oxidative and radical-mediated damage, provided that the efficacy of these mechanisms is not overwhelmed by very high concentrations of these toxins or by a lack of energy required for their optimal function (Marker et al, 1981;Hothershall et al, 1982;DeVito and Wagner, 1989;Swanson and Choi, 1993). That the exhaustion of endogenous defense mechanisms may indeed represent the most crucial factor in the sequence of events which lead to the degeneration of 5-HT terminals and axons after administration of substituted amphetamines is supported by direct evidence for oxidative stress and radicalmediated damage (Stone et al, 1989;Gudelsky et al, 1994;Sprague and Nichols, 1995) and by the observed protective action of antioxidants and radical scavengers Hirata et al, 1995;Gudelsky, 1996).…”