The effect of hyperglycaemia on parameters affecting activity of pentose phosphate pathway in vitro

Authors

KURICOVÁ Katarína PÁCAL Lukáš KNOPFOVÁ Lucia TOMANDL Josef TANHÄUSEROVÁ Veronika KAŇKOVÁ Kateřina

Year of publication 2012
Type Conference abstract
Citation
Description Pentose phosphate pathway (PPP) with a rate-limiting enzyme transketolase (TKT) as a key regulator represents one of the few potentially protective metabolic pathways in hyperglycaemic conditions. TKT activation leads to the increased processing of glycolytic metabolites through the PPP and limits their flux through other harmful pathways activated by hyperglycaemia. TKT activity depends on the availability of its cofactor thiamine diphosphate (ThDP). ThDP is derived from thiamine by the action of intracellular enzyme thiamine pyrophosphokinase (TPK). Thiamine and thiamine esters enter the cell via specific membrane transporters. Our group have demonstrated rise of plasma thiamines in subjects with decreased renal function (plasma thiamines being inversely correlated with GFR), however, erythrocyte ThDP levels were decreased correspondingly to GFR and did not correspond with TKT activity. Since intracellular deficiency of ThDP does not seem to be a consequence of decreased plasma levels of its precursors we propose that major abnormalities in thiamine metabolism most likely take place on the level of transport between extra- and intracellular compartment and within the cells.
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