(NASDAQ: AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, today announced that new data from the core and extension phases of the DRIVE PK Phase 2 study of mitapivat (AG-348) in adults with
pyruvate kinase (PK) deficiency were published in the September 5, 2019 issue of theNew England Journal of Medicine.
In addition to maintaining intracellular redox balance, malate produced in the aforementioned process is also converted to
pyruvate by ME1.
Lactic acidosis and PAA along with the MRI findings prompted the differential diagnosis of
pyruvate carboxylase deficiency (PCD), which was confirmed by PC gene sequencing.
Liver glucose release in the presence of lactate+ glycerol was similar in all groups (P > 0.05, Figure 4B), but
pyruvate release was reduced in the trained groups, being significantly lower in group TI compared with group SS (Figure 4C).
Qu's team was surprised to find that
pyruvate is critical for neural precursor/stem cells, even though they are not dividing quickly and it was the defects in these cells that caused complete block in cerebellar development in PTPMT1-deleted mice In contrast, rapidly proliferating granule cells, a distinctively small type of cell found in the cerebellum, are not affected as much by the deletion.
In our study, we evaluated the effects of unilateral fornix DBS on glucose metabolism changes by intracerebral microdialysis, and we then tested the levels of extracellular glucose, lactate, and
pyruvate in the hippocampus in both aged and adult mice.
However, it will take time for such treatment to become available for clinical use; therefore, we propose the administration of
pyruvate or mitochonic acid 5 (MA-5) as a practical means to promote muscle regeneration and energy production.
As hair follicle stem cells consume the nutrient glucose from the bloodstream, they process the glucose to eventually produce a metabolite called
pyruvate.
The molecular basis of these adaptations in the pika have occurred because of a series of genetic evolutionary changes, including HIF-1 a (Li et al., 2009; Zhao et al., 2004), hemoglobin (Yang et al., 2007), vascular endothelial growth factor (VEGF) (Li et al., 2013; Zheng et al., 2011) testis-specific lactate dehydrogenase (LDH-C4) (Wang et al., 2013),
pyruvate carboxylase (Sun et al., 2013), myoglobin (Qi et al., 2008), cytochromec oxidase (Luo et al., 2008), neuron nitric oxide synthase (nNOS) (Pichon et al., 2009), and leptin (Yang et al., 2006, 2008).
The deleted region involved a new gene that could be responsible for the clinical manifestations including cleft palate and Molar tooth sign,
pyruvate dehydrogenase phosphatase regulatory subunit (PDPR).
In the two diseases, upregulation of the canonical Wnt system leads to activation of
pyruvate dehydrogenase kinase (PDK), which decreases the activity of the
pyruvate dehydrogenase complex (PDH).
Lactate, a 3-carbon hydroxycarboxylic acid, is produced in the cytoplasm by the glycolysis pathway under anaerobic conditions, via the reduction of an intermediate metabolite
pyruvate, with the simultaneous oxidation of NADH to NAD+.
The following chemicals were used in the experiments: D-glucose, L-leucine, L-glutamine,
pyruvate, L-lactate, IBMX, and forskolin (Sigma-Aldrich, Taufkirchen, Germany), mannoheptulose (Bujno Synthesis, Warsaw, Poland), glibenclamide (Santa Cruz Biotechnology, Dallas, USA), and Bay K 8644 (Alomone Labs, Jerusalem, Israel).
