pyruvate dehydrogenase kinase isozymes 1, 2, 3, 4, PDK1, PDK2, PDK3, PDK4, PDHK1, PDHK2, PDHK3, PDHK4
pyruvate dehydrogenase phosphatase 1, 2, PDP1, PDP2
|Structure and Function:||
The pyruvate dehydrogenase complex (PDH) is at the centre of aerobic carbohydrate metabolism. It is localized in the matrix space of mitochondria where it catalyzes the irreversible oxidative decarboxylation of pyruvate entering the organelle to produce acetyl-CoA, NADH and CO2. Thus, it links and regulates the flow of energy in cells by determining when pyruvate should be used for oxidative phosphorylation versus "neutralized" to lactic acid to allow continued glycolysis. At the same time the control of acetyl Co-A directly influences fatty acid oxidation and production of ketone bodies.
The activity of PDH is regulated by reversible phosphorylation of three serine residues on the E1α subunit. The phosphorylation of these sites is catalyzed by PDH kinases (PDK). There are four known isoforms of PDKs that are distributed differently in tissues. Their expressions are regulated differently by factors such as starvation, hypoxia and utilization of glucose and fatty acids in various tissues. In addition, transcription regulators such as PGC-1α, retinoic acid and the glucocorticoid receptor are involved.
Dephosporylation to restore the activity of PDH is catalyzed by PDH phosphatases (PDP). There are two known isoforms of PDPs, which are expressed differently in various tissues; PDP1 is present in high levels in skeletal muscle and PDP2 in liver and adipocytes.
|Disease Associations:||PDH deficiencies, diabetes, starvation, sepsis, cancer metabolism, and possibly Alzheimer's have been linked to altered PDH functioning.|