Manganese in Metabolism

[percyval577]

This article from 2004 is in so far outdated as Manganism (as well as Parkinsonism) is not concidered anymore to have cell death invovlved, as far as I know. However, the other finding might be interesting for ME/CFS, albeit not in very high (or for longer quite high) dose exposures:
So, Comhaire and Deslypere (accepted 2019 // 2020) News and Views in [ME/CFS]: The role of co-morbidity and novel treatments say that immune derugulation might not be the cause but an association with the mechanism in ME/CFS, and that their imaging would correlate with disproportionate energy production by the neurons. Recent findings would point to the direction of impaired cellular glucose metabolism, and enzymatic failure might also occur in the Krebs cycle itself (pages 3-4).


Differential lowering by manganese treatment of activities of glycolytic and tricarboxylic acid (TCA) enzymes investigated in neuroblastoma and astrocytoma is associated with manganese-induced cell death
Malthanka et al 2004


Abstract (my prgrphs)

Manganese (Mn) is a trace metal required for normal growth and development. Manganese neurotoxicity is rare and usually associated with occupational exposures. However, the cellular and molecular mechanisms underlying Mn toxicity are still elusive. In rats chronically exposed to Mn, their brain regional Mn levels increase in a dose-related manner. Brain Mn preferentially accumulates in mitochondria; this accumulation is further enhanced with Mn treatment in vivo.

Exposure of mitochondria to Mn in vitro leads to uncoupling of oxidative phosphorylation. These observations prompted us to investigate the hypothesis that Mn induces alterations in energy metabolism in neural cells by interfering with the activities of various glycolytic and TCA cycle enzymes using human neuroblastoma (SK-N-SH) and astrocytoma (U87) cells.

Treatments of SK-N-SH and U87 cells with MnCl2 induced cell death in these cells, in a concentration- and time-dependent manner, as determined by MTT assays. In parallel with the Mn-induced, dose-dependent decrease in cell survival, treatment of these cells with 0.01 to 4.0 mM MnCl2 for 48 h also induced dose-related decreases in their activities of hexokinase, pyruvate kinase, lactate dehydrogenase, citrate synthase, and malate dehydrogenase.

Hexokinase in SK-N-SH cells was the most affected by Mn treatments, even at the lower range of concentrations. Mn treatment of SK-N-SH cells affected pyruvate kinase and citrate synthase to a lesser extent as compared to its effect on other enzymes investigated. However, citrate synthase and pyruvate kinase in U87 cells were more vulnerable than other enzymes investigated to the effects of Mn. The results suggest the two cell types exhibited differential susceptibility toward the Mn-induced effects. Additionally, the results may have significant implications in flux control because HK is the first and highly regulated enzyme in brain glycolysis. Thus these results are consistent with our hypothesis and may have pathophysiological implications in the mechanisms underlying Mn neurotoxicity.[/QUOT]

paywalled
Neurochem Res. 2004 Apr;29(4):709-17.​