Deficiency of thiamine leads to decreased activity of the enzyme transketolase
in the absence of which there is reduced activity of the pentose phosphate pathway leading to the accumulation of deleterious products of glucose metabolism like ROS, AGEs, PKC etc.
SIDMAP approaches now have shown that cells develop Gleevec resistance by enhancing the activity of the non-oxidative portion of the pentose phosphate pathway (which involves the transketolase
enzyme), which is not appreciably inhibited by Gleevec.
In one study, benfotiamine activated the important enzyme transketolase
, which rapidly cleared AGEs from the blood before they could damage kidney tissue.
The first part of the in vitro study is to ascertain the concentration of the product of the enzyme, measured in units and reported as transketolase
These enzymes are called transketolase
, pyruvate dehydrogenase (PDH) and alphaketoglutarate dehydrogenase ([alpha]-KGDH); they all participate in the catabolism of sugar molecules (i.
Thiamin deficiency was diagnosed: serum thiamin 34 U (normal range 50 to 100 U) red cell transketolase
stimulation 17% (marginal deficiency 15 to 22%).
The experimental group became thiamine deficient measured by transketolase
with increased oxidative stress measured by reduced GSH.
is an enzyme that directs the precursors of advanced glycation end products (AGEs) to pentose phosphate pathway.
Thiamin diphosphate (TPP), the active form of thiamine, comprising over 80% of the body stores, functions as a cofactor in enzymatic reactions that cleave alpha-keto acids (decarboxylation reactions), which includes transketolase
, pyruvate dehydrogenase, [alpha]-oxoglutarate dehydrognease and the branched-chain a-oxoacid dehydrogenase complex, as well as enzymes of both the pentose phosphate pathway and the citric acid cycle.
In the PPP, glu-6P is first converted into pentose 5-phosphates, which are subsequently recycled to glu-6P by two enzymes: transketolase
and transaldolase (TALDO; Fig.