Answer Explanations 4

I cannot answer
Expert 10
Kinetics of 1-3D show non-linearity that is representative of enzymatic saturation or cofactor depletion. To distinguish between the two, an enzyme kinetic for GST pathway could have been made to determine if saturation could explain the observed non-linearity. Data shown in figure 2, show roughly a 50% depletion of GSH in lungs, but this uncertain if this is sufficient to explain this non-linearity.
Yes
Expert 13
It is clear that the levels of GSH in this portal-of-entry tissue were significantly depleted at 30 ppm and above. This depletion is consistent with the requirement of glutathione for 1,3-D metabolic clearance. Similar depletion has been found following repeated inhalation exposures to chemicals that undergo glutathione based metabolism such as ethylene oxide, propylene oxide, naphthalene etc.,
Yes
Expert 5
The non linearity in the clearance of 1,3-D is consistent with saturation of GSH conjugation. This suggests GSH conjugation being a predominant metabolic pathway.
Yes
Expert 12
The main metabolites found in the urine are in accordance with the GSH metabolic pathway. Furthermore, there is a direct effect of the GSH depletion on the blood kinetics of the compound. Accordingly, the relevant nonlinearity that was observed in the blood kinetics between about 10-60 ppm is quite consistent with the depletion of glutathione between about 10-60 ppm reported in lung tissues.
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Expert 12
04/17/2019 11:05

No more comment from my side since there is nobody saying clearly that GSH cannot be depleted.

0
Expert 10
04/23/2019 10:03

There is not much to debate on this question.

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