PDK3

The pyruvate dehydrogenase (PDH) complex is a nuclear-encoded mitochondrial multienzyme complex that catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2). It provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle, and thus is one of the major enzymes responsible for the regulation of glucose metabolism. The enzymatic activity of PDH is regulated by a phosphorylation/dephosphorylation cycle, and phosphorylation results in inactivation of PDH. The protein encoded by this gene is one of the three pyruvate dehydrogenase kinases that inhibits the PDH complex by phosphorylation of the E1 alpha subunit. This gene is predominantly expressed in the heart and skeletal muscles.

Full Name

Pyruvate Dehydrogenase Kinase 3

Function

Inhibits pyruvate dehydrogenase activity by phosphorylation of the E1 subunit PDHA1, and thereby regulates glucose metabolism and aerobic respiration. Can also phosphorylate PDHA2. Decreases glucose utilization and increases fat metabolism in response to prolonged fasting, and as adaptation to a high-fat diet. Plays a role in glucose homeostasis and in maintaining normal blood glucose levels in function of nutrient levels and under starvation. Plays a role in the generation of reactive oxygen species.

Biological Process

Cellular response to fatty acidManual Assertion Based On ExperimentIMP:UniProtKB
Cellular response to glucose stimulusISS:UniProtKB
Glucose metabolic processIEA:UniProtKB-KW
Hypoxia-inducible factor-1alpha signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Peptidyl-serine phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Peroxisome proliferator activated receptor signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Protein phosphorylationManual Assertion Based On ExperimentIBA:GO_Central
Regulation of acetyl-CoA biosynthetic process from pyruvateManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of glucose metabolic processManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of reactive oxygen species metabolic processManual Assertion Based On ExperimentIMP:UniProtKB

Cellular Location

Mitochondrion matrix

Involvement in disease

Charcot-Marie-Tooth disease, X-linked dominant, 6 (CMTX6):
A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies characterized by severely reduced motor nerve conduction velocities (NCVs) (less than 38m/s) and segmental demyelination and remyelination, and primary peripheral axonal neuropathies characterized by normal or mildly reduced NCVs and chronic axonal degeneration and regeneration on nerve biopsy.