The main function of the pathway is the generation of a molecule called adenosine triphosphate (ATP), which provides energy for numerous cellular processes and reactions.20 A decrease in ATP production in the brain leads to an increase in production of toxic metabolites of dopamine and inhibition of catechol-O-methyl transferase (COMT) activities, which is a vital enzyme for synthesis and breakdown of dopamine in the prefrontal cortex.[21,22] Thus, an increase in the level of dopamine may lead to delirium, including hallucinations and delusions.[22] In addition, proper functioning of PDH is essential for the production of the neurotransmitter acetylcholine as well as for the synthesis of myelin.20 Low levels of acetylcholine have been linked to delirium as well as the severity of cognitive impairment associated with delirium.[14,23] The citric acid cycle and alpha-KGDH play a role in maintaining the levels of the glutamate, gamma aminobutyric acid (GABA), and aspartate.[24,25] GABA is a major inhibitory neurotransmitter in the brain, and a decrease in the levels of this neurotransmitter and an increase in its amino acid precursor, glutamine, leads to neuronal excitation and hence delirium.[14] Pentose phosphate pathway (PPP) is a very important pathway that occurs in the cytosol of human cells, including the brain, and serves as an alternative pathway to glycolysis.[26] Transketolase is an important enzyme in the pentose phosphate pathway that requires thiamine as a cofactor, modifying a molecule called glucose-6-phosphate, which is derived from glucose
However, this inhibitory effect on LR is only present within the first 48 h (as observed with BrdU-positive hepatocytes) (Sekine et al., 2007)
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