Pyruvate Dehydrogenase Complex Regulation and Lipoic Acid

2008 ◽  
Author(s):  
Mulchand Patel ◽  
Lioubov Korotchkina
Keyword(s):  
Lipoic Acid ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Complex Regulation ◽  
Dehydrogenase Complex

Interaction of α-Lipoic acid enantiomers and homologues with the enzyme components of the mammalian pyruvate dehydrogenase complex

1995 ◽  
Vol 50 (5) ◽  
pp. 637-646 ◽  
Author(s):  
Sabine Löffelhardt ◽  
Christoph Bonaventura ◽  
Mathias Locher ◽  
Harald O. Borbe ◽  
Hans Bisswanger
Keyword(s):  
Lipoic Acid ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Dehydrogenase Complex

scholarly journals α-Lipoic acid promotes α-tubulin hyperacetylation and blocks the turnover of mitochondria through mitophagy

2016 ◽  
Vol 473 (12) ◽  
pp. 1821-1830 ◽  
Author(s):  
Michael W. Stoner ◽  
Dharendra Thapa ◽  
Manling Zhang ◽  
Gregory A. Gibson ◽  
Michael J. Calderon ◽  
...  
Keyword(s):  
Lipoic Acid ◽  
Pyruvate Dehydrogenase ◽  
Metabolic Pathways ◽  
Pyruvate Dehydrogenase Complex ◽  
Lysine Acetylation ◽  
Acetyl Coa ◽  
Chemical Inducers ◽  
Tightly Coupled ◽  
Metabolic Conditions ◽  
Dehydrogenase Complex

Lysine acetylation is tightly coupled to the nutritional status of the cell, as the availability of its cofactor, acetyl-CoA, fluctuates with changing metabolic conditions. Recent studies have demonstrated that acetyl-CoA levels act as an indicator of cellular nourishment, and increased abundance of this metabolite can block the induction of cellular recycling programmes. In the present study we investigated the cross-talk between mitochondrial metabolic pathways, acetylation and autophagy, using chemical inducers of mitochondrial acetyl-CoA production. Treatment of cells with α-lipoic acid (αLA), a cofactor of the pyruvate dehydrogenase complex, led to the unexpected hyperacetylation of α-tubulin in the cytosol. This acetylation was blocked by pharmacological inhibition of mitochondrial citrate export (a source for mitochondria-derived acetyl-CoA in the cytosol), was dependent on the α-tubulin acetyltransferase (αTAT) and was coupled to a loss in function of the cytosolic histone deacetylase, HDAC6. We further demonstrate that αLA slows the flux of substrates through autophagy-related pathways, and severely limits the ability of cells to remove depolarized mitochondria through PTEN-associated kinase 1 (PINK1)-mediated mitophagy.

scholarly journals Lipoic acid residues in a take-over mechanism for the pyruvate dehydrogenase multienzyme complex of Escherichia coli

1981 ◽  
Vol 199 (3) ◽  
pp. 513-520 ◽  
Author(s):  
J N Berman ◽  
G X Chen ◽  
G Hale ◽  
R N Perham
Keyword(s):  
Escherichia Coli ◽  
Lipoic Acid ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Pyruvate Decarboxylase ◽  
Enzymic Activity ◽  
Enzyme Mechanism ◽  
Enzyme Complex ◽  
Complex Activity ◽  
Dehydrogenase Complex

The pyruvate dehydrogenase complex of Escherichia coli contains two lipoic acid residues per dihydrolipoamide acetyltransferase chain, and these are known to engage in the part-reactions of the enzyme. The enzyme complex was treated with trypsin at pH 7.0, and a partly proteolysed complex was obtained that had lost almost 60% of its lipoic acid residues although it retained 80% of its pyruvate dehydrogenase-complex activity. When this complex was treated with N-ethylmaleimide in the presence of pyruvate and the absence of CoASH, the rate of modification of the remaining S-acetyldihydrolipoic acid residues was approximately equal to the accompanying rate of loss of enzymic activity. This is in contrast with the native pyruvate dehydrogenase complex, where under the same conditions modification proceeds appreciably faster than the loss of enzymic activity. The native pyruvate dehydrogenase complex was also treated with lipoamidase prepared from Streptococcus faecalis. The release of lipoic acid from the complex followed zero-order kinetics for most of the reaction, whereas the accompanying loss of pyruvate dehydrogenase-complex activity lagged substantially behind. These results eliminate a model for the enzyme mechanism in which specifically one of the two lipoic acid residues on each dihydrolipoamide acetyltransferase chain is essential for the reaction. They are consistent with a model in which the dihydrolipoamide acetyltransferase component contains more lipoic acid residues than are required to serve the pyruvate decarboxylase subunits under conditions of saturating substrates, enabling the function of an excised or inactivated lipoic acid residue to be taken over by another one. Unusual structural properties of the enzyme complex might permit this novel feature of the enzyme mechanism.

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