Mitapivat is an investigational, first-in-class, oral, small molecule allosteric activator of wild-type and a variety of mutated pyruvate kinase-R (PKR) enzymes that directly targets the underlying metabolic defect in PK deficiency, a rare, potentially debilitating, hemolytic anemia.

Structures of the human pyruvate dehydrogenase complex cores: a highly conserved catalytic center with flexible N-terminal domains.

Liver lactate and pyruvate release in the presence of alanine+ glutamine was decreased by about 50% in the trained groups (Figure 5C and D, respectively).

The concentrations of glucose, lactate, pyruvate, and glutamate in dialysate samples were analyzed in the ISCUS microdialysis analyzer (ISCUS flex, Sweden) by batch analysis using standard ISCUS reagents.

Thus, pyruvate administration restores adenosine 5'-triposphate (ATP) production via the glycolytic pathway.

The cells then can either send pyruvate to their energy-generating mitochondria or can convert pyruvate into another metabolite called lactate.

The lactate dehydrogenase (LDH) family enzymes catalyze the inter-conversion of pyruvate to lactate with the concomitant oxidation/reduction of NADH to NAD+ (Everse and Kaplan, 1973).

As a consequence, in the Warburg effect, a large part of cytosolic pyruvate is not converted into acetyl-CoA which does not enter the TCA cycle.

Lactate is transported across the plasma membrane with the aid of the monocarboxylate transporters (MCTs), which facilitates the proton-linked transport of monocarboxylates, for example, L-lactate, pyruvate, and the ketone bodies [20, 21].

In the presence of 10 mM glucose, pyruvate (10 mM) addition caused a minimal increase of the insulin secretory rate and lactate (10 mM) had no effect (Figures 5(a) and 5(b)).