Abstract:
Pyruvate dehydrogenase (PDH) plays an important role in regulating carbohydrate
oxidation in skeletal muscle. PD H is deactivated by a set of PD H kinases (PD K 1-4) with
PDK2 and 4 being the predominant isoforms in skeletal muscle. PDK2 is highly sensitive
to pyruvate inhibition, and is the most abundant isoform, while PDKI and 4 protein
content are normally lower. This study examined the PDK isoform content and PDHa
activation in muscle at rest and 10 and 40 Hz stimulation from PDK2 knockout
(PDK2KO) mice to delineate the role of PDK2 in activating the PDH complex during
low and moderate intensity muscle contraction. PDHa activity was lower in PDK2KO
mice during contraction while total PDK actitvity was -4 fold lower. PDK4 protein was
not different, however PDKI partially compensated for the lack of PDK2 and was -56%
higher than WT. PDKI is a very potent inhibitor of the PDH complex due to its
phosphorylation site specificity and allosteric regulation. These results suggest that the
site specificity and allosteric regulatory properties of the individual PDK isoforms are
more important than total PDK activity in determining transformation of the complex and
PDHa activity during acute muscle contraction.
