How does pyruvate dehydrogenase work?
The pyruvate dehydrogenase complex (PDC)3 catalyzes the oxidative decarboxylation of pyruvate with the formation of acetyl-CoA, CO2 and NADH (H+) (1,–3). The PDC occupies a key position in the oxidation of glucose by linking the glycolytic pathway to the oxidative pathway of the tricarboxylic acid cycle.
What are the steps of pyruvate dehydrogenase complex?
In the reaction sequence catalyzed by components of the pyruvate dehydrogenase complex, pyruvate dehydrogenase catalyzes the first two steps, namely:
- the decarboxylation of pyruvate to form CO2 and the hydroxyethyl-TPP intermediate;
- the reductive acetylation of the lipoyl group of dihydrolipoyl transacetylase.
What are the three reactions catalyzed by pyruvate dehydrogenase?
1 The Intermediates Are Covalently Bound Sequentially to Active Sites. Pyruvate dehydrogenase complex is a multifunctional enzyme complex which catalyzes oxidative decarboxylation of pyruvate to acetyl-CoA, NADH, and CO2.
What is the name of the mechanism by which pyruvate dehydrogenase is inhibited by the end product of the biochemical pathway?
The mechanisms that control PDC activity include end product inhibition by increased mitochondrial acetyl-CoA, NADH and ATP concentrations (which can also be generated by FA oxidation) and post-translational modification, namely its phosphorylation (inactivation) by a family of pyruvate dehydrogenase kinases (PDHKs 1–4 …
What does pyruvate dehydrogenase kinase do?
Pyruvate dehydrogenase kinase (PDK) is a kinase that inactivates the pyruvate dehydrogenase enzyme complex through phosphorylation. By downregulating the activity of this complex, PDK decreases the oxidation of pyruvate in mitochondria and increases the conversion of pyruvate to lactate in the cytosol.
What is pyruvate dehydrogenase activated by?
Pyruvate dehydrogenase kinase is activated by ATP, NADH and acetyl-CoA. It is inhibited by ADP, NAD+, CoA-SH and pyruvate.
Why are steps 4 and 5 essential to the operation of the PDH complex?
The remainder of the reactions catalyzed by the pyruvate dehydrogenase complex (steps 4 and 5) are electron transfers necessary to regenerate the disulfide form of the lipoyl group of E2 to prepare the enzyme complex for another round of oxidation.
Does pyruvate inhibit PDH?
PDH kinase is stimulated by NADH and acetyl-CoA. It is inhibited by pyruvate.
How is pyruvate dehydrogenase inhibited?
Pyruvate dehydrogenase is regulated by end product inhibition by acetyl CoA (competitive with CoA) , NADH 2 (competitive NAD) and acetoin (competitive pyruvate); and through inactivation by phosphorylation catalysed by an intrinsic kinase utilising ATPMg++ and reactivation by a phosphatase.
How does DCA acts to stimulate pyruvate dehydrogenase activity?
DCA targets the activity of pyruvate dehydrogenase kinase (PDK) Identify how DCA acts to stimulate pyruvate dehydrogenase activity: DCA activates pyruvate dehydrogenase phosphatase DCA increases phosphorylation levels of pyruvate dehydrogenase.