In the present study, DEGs were enriched in amino acid metabolism pathways include GOT1, MDH1, monocarboxylate transporter 4 (SLC16A3),
pyruvate dehydrogenase 1 (PDHA1), and
pyruvate dehydrogenase kinase 4 (PDK4).
The PDK4 protein located in mitochondria and inhibiting the catalyzing function of
pyruvate dehydrogenase (PDH) (Grassian et al., 2011).
Whereas
pyruvate dehydrogenase kinase 3 (PDK3) was upregulated,
pyruvate dehydrogenase phosphatase 1 (PDP1) and dihydrolipoamide dehydrogenase (DLD) were downregulated.
Pyruvate dehydrogenase (PDH) inactivation from phosphorylation by
pyruvate dehydrogenase kinases (PDKs) prevents pyruvate from entering the mitochondrial Krebs cycle [45].
Pyruvate is decarboxylated by
pyruvate dehydrogenase (PDH) to acetyl-CoA, which is then condensed with oxalacetate to citrate via the citrate synthase (CS).
(1) It is reduced to form lactate and NAD+; (2) it is oxidized by
pyruvate dehydrogenase complex (PDHC) to yield acetyl-CoA; and (3) it is carboxylated by pyruvate carboxylase to form oxaloacetate for the anaplerosis to replenish tricarboxylic acid (TCA) cycle intermediates.
monodon succinyltransferase GE615760.1 -
Pyruvate dehydrogenase complex
Pyruvate dehydrogenase El L.
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).
Pyruvate dehydrogenase kinase (PDK) enhances phosphorylation and inactivation of the
pyruvate dehydrogenase complex, which occupies a strategic role in various substrate and hormonal processes (10).
Thiamine acts as a cofactor for various enzymes involved in aerobic metabolism, such as
pyruvate dehydrogenase. Therefore, its deficiency promotes anaerobic metabolism, which results in the production of lactate (3).
This alteration leads to the accumulation of malate, reduces
pyruvate dehydrogenase activity and increases the activity of malic and pyruvate decarboxylase enzymes, thus increasing the formation of acetaldehyde.
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).