Pyruvate dehydrogenase (acetyl-transferring)
Pyruvate dehydrogenase E1 ( PDHE1 ) is the name for the E1 subunit of pyruvate dehydrogenase enzyme complex. PDHE1 catalyzes the transfer of an acetyl residue bonded to the sub-unit E2 lipoyllysine, wherein one molecule of carbon dioxide is released. E1 consists of two α and two β subunits. Of α there is a second human isoform that is specifically expressed in the testis. Mutations in the genes that encode α and β ( in α alone are 80 known), PDHE1 deficiency can cause up to Leigh syndrome and lactic acidosis.
The decarboxylation of pyruvate is the thiamine rather than catalytic center, which forms an atom binding with pyruvate, so that hydroxy -ethylidene- thiamine pyrophosphate is formed with elimination of CO2.
⇒ ⇒ CO2 (R = CH3)
This hydroxy -ethylidene radical (syn. acetaldehyde ) of the TPP is taken from the α -lipoic acid ( oxidation). Is covalently bound to the trans- acetylase lipoate subunit. The result is S -acetyl- Hydrolip ( oat / onamid ).
⇒ (R = CH3)
It seems that the two molecules in the tetramer thiamine not simultaneously pass through the said reaction sequence. In a crystal study a related motion of the tetramer was found.
The testis -specific isoform of the enzyme plays a role in after capacitation, a study on hamsters.
PDHE1 is inactivated by phosphorylation of the α - unit or activated by dephosphorylation. The corresponding enzyme is PDH kinase ( EC 18.104.22.168 ) which is a part of the PDH itself ( autophosphorylation = ). Increased activity can already be triggered by increased muscle work, with a dependence of the PDH phosphatase is discussed by the mitochondrial Ca2 concentration. Inhibition by sepsis could be shown in rats.