Pyruvate dehydrogenase activity in response to skeletal muscle contraction at two stimulation frequencies in pyruvate dehydrogenase kinase 2 knockout mice

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.

Name thesis:degree_name

M.Sc. Applied Health Sciences

Level thesis:degree_level

Masters

Discipline thesis:degree_discipline

Faculty of Applied Health Sciences

Department dc:contributor.department

Applied Health Sciences Program

Grantor

Brock University

Year dc:date.issued

2009

Author dc:creator

• Dunford, Emily.

• Muscles--Metabolism.
• Pyruvate kinase.
• Muscle contraction.

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/10464/2914

OAI identifier oai:identifier

oai:brocku.scholaris.ca:10464/2914