scholarly journals Acetyl-Coenzyme A Can Regulate Activity of the Mitochondrial Pyruvate Dehydrogenase Complex in Situ

1991 ◽  
Vol 95 (1) ◽  
pp. 131-136 ◽  
Author(s):  
Raymond J. A. Budde ◽  
Tung K. Fang ◽  
Douglas D. Randall ◽  
Jan A. Miernyk
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Coenzyme A ◽  
Pyruvate Dehydrogenase Complex ◽  
Acetyl Coenzyme A ◽  
Acetyl Coenzyme ◽  
Dehydrogenase Complex

scholarly journals Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases

2021 ◽  
Vol 22 (2) ◽  
pp. 764
Author(s):  
Russel J. Reiter ◽  
Ramaswamy Sharma ◽  
Sergio Rosales-Corral
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Warburg Effect ◽  
Coenzyme A ◽  
Aerobic Glycolysis ◽  
Pyruvate Dehydrogenase Complex ◽  
Pyruvate Dehydrogenase Kinase ◽  
Metabolic Phenotype ◽  
Common Denominator ◽  
Acetyl Coenzyme A ◽  
Acetyl Coenzyme

Glucose is an essential nutrient for every cell but its metabolic fate depends on cellular phenotype. Normally, the product of cytosolic glycolysis, pyruvate, is transported into mitochondria and irreversibly converted to acetyl coenzyme A by pyruvate dehydrogenase complex (PDC). In some pathological cells, however, pyruvate transport into the mitochondria is blocked due to the inhibition of PDC by pyruvate dehydrogenase kinase. This altered metabolism is referred to as aerobic glycolysis (Warburg effect) and is common in solid tumors and in other pathological cells. Switching from mitochondrial oxidative phosphorylation to aerobic glycolysis provides diseased cells with advantages because of the rapid production of ATP and the activation of pentose phosphate pathway (PPP) which provides nucleotides required for elevated cellular metabolism. Molecules, called glycolytics, inhibit aerobic glycolysis and convert cells to a healthier phenotype. Glycolytics often function by inhibiting hypoxia-inducible factor-1α leading to PDC disinhibition allowing for intramitochondrial conversion of pyruvate into acetyl coenzyme A. Melatonin is a glycolytic which converts diseased cells to the healthier phenotype. Herein we propose that melatonin’s function as a glycolytic explains its actions in inhibiting a variety of diseases. Thus, the common denominator is melatonin’s action in switching the metabolic phenotype of cells.

scholarly journals Engineering Acetyl Coenzyme A Supply: Functional Expression of a Bacterial Pyruvate Dehydrogenase Complex in the Cytosol of Saccharomyces cerevisiae

mBio ◽  
2014 ◽  
Vol 5 (5) ◽  
Author(s):  
Barbara U. Kozak ◽  
Harmen M. van Rossum ◽  
Marijke A. H. Luttik ◽  
Michiel Akeroyd ◽  
Kirsten R. Benjamin ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Pyruvate Dehydrogenase ◽  
Coenzyme A ◽  
Pyruvate Dehydrogenase Complex ◽  
Baker’S Yeast ◽  
Baker's Yeast ◽  
Acetyl Coa ◽  
Acetyl Coenzyme A ◽  
Content Type ◽  
Acetyl Coenzyme

ABSTRACTThe energetic (ATP) cost of biochemical pathways critically determines the maximum yield of metabolites of vital or commercial relevance. Cytosolic acetyl coenzyme A (acetyl-CoA) is a key precursor for biosynthesis in eukaryotes and for many industrially relevant product pathways that have been introduced intoSaccharomyces cerevisiae, such as isoprenoids or lipids. In this yeast, synthesis of cytosolic acetyl-CoA via acetyl-CoA synthetase (ACS) involves hydrolysis of ATP to AMP and pyrophosphate. Here, we demonstrate that expression and assembly in the yeast cytosol of an ATP-independent pyruvate dehydrogenase complex (PDH) fromEnterococcus faecaliscan fully replace the ACS-dependent pathway for cytosolic acetyl-CoA synthesis.In vivoactivity ofE. faecalisPDH required simultaneous expression ofE. faecalisgenes encoding its E1α, E1β, E2, and E3 subunits, as well as genes involved in lipoylation of E2, and addition of lipoate to growth media. A strain lacking ACS that expressed theseE. faecalisgenes grew at near-wild-type rates on glucose synthetic medium supplemented with lipoate, under aerobic and anaerobic conditions. A physiological comparison of the engineered strain and an isogenic Acs+reference strain showed small differences in biomass yields and metabolic fluxes. Cellular fractionation and gel filtration studies revealed that theE. faecalisPDH subunits were assembled in the yeast cytosol, with a subunit ratio and enzyme activity similar to values reported for PDH purified fromE. faecalis. This study indicates that cytosolic expression and assembly of PDH in eukaryotic industrial microorganisms is a promising option for minimizing the energy costs of precursor supply in acetyl-CoA-dependent product pathways.IMPORTANCEGenetically engineered microorganisms are intensively investigated and applied for production of biofuels and chemicals from renewable sugars. To make such processes economically and environmentally sustainable, the energy (ATP) costs for product formation from sugar must be minimized. Here, we focus on an important ATP-requiring process in baker’s yeast (Saccharomyces cerevisiae): synthesis of cytosolic acetyl coenzyme A, a key precursor for many industrially important products, ranging from biofuels to fragrances. We demonstrate that pyruvate dehydrogenase from the bacteriumEnterococcus faecalis, a huge enzyme complex with a size similar to that of a ribosome, can be functionally expressed and assembled in the cytosol of baker’s yeast. Moreover, we show that this ATP-independent mechanism for cytosolic acetyl-CoA synthesis can entirely replace the ATP-costly native yeast pathway. This work provides metabolic engineers with a new option to optimize the performance of baker’s yeast as a “cell factory” for sustainable production of fuels and chemicals.

scholarly journals The Role of Pyruvate Dehydrogenase and Acetyl-Coenzyme A Synthetase in Fatty Acid Synthesis in Developing Arabidopsis Seeds

2000 ◽  
Vol 123 (2) ◽  
pp. 497-508 ◽  
Author(s):  
Jinshan Ke ◽  
Robert H. Behal ◽  
Stephanie L. Back ◽  
Basil J. Nikolau ◽  
Eve Syrkin Wurtele ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Pyruvate Dehydrogenase ◽  
Coenzyme A ◽  
Acid Synthesis ◽  
Acetyl Coenzyme A ◽  
Acetyl Coenzyme

scholarly journals Electron microscopic study on the size of pyruvate dehydrogenase complex in situ

1987 ◽  
Vol 169 (1) ◽  
pp. 223-230 ◽  
Author(s):  
Balazs SUMEGI ◽  
Zsolt LIPOSITS ◽  
Lindsey INMAN ◽  
Willis K. PAULL ◽  
Paul A. SRERE
Keyword(s):  
Microscopic Study ◽  
Electron Microscopic Study ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Electron Microscopic ◽  
Dehydrogenase Complex

scholarly journals Synthetic Biology for Engineering Acetyl Coenzyme A Metabolism in Yeast

mBio ◽  
2014 ◽  
Vol 5 (6) ◽  
Author(s):  
Jens Nielsen
Keyword(s):  
Coenzyme A ◽  
Pyruvate Dehydrogenase Complex ◽  
High Yield ◽  
Cell Factory ◽  
Efficient Production ◽  
Acetyl Coa ◽  
Acetyl Coenzyme A ◽  
Content Type ◽  
Acetyl Coenzyme ◽  
High Yields

ABSTRACT The yeast Saccharomyces cerevisiae is a widely used cell factory for the production of fuels, chemicals, and pharmaceuticals. The use of this cell factory for cost-efficient production of novel fuels and chemicals requires high yields and low by-product production. Many industrially interesting chemicals are biosynthesized from acetyl coenzyme A (acetyl-CoA), which serves as a central precursor metabolite in yeast. To ensure high yields in production of these chemicals, it is necessary to engineer the central carbon metabolism so that ethanol production is minimized (or eliminated) and acetyl-CoA can be formed from glucose in high yield. Here the perspective of generating yeast platform strains that have such properties is discussed in the context of a major breakthrough with expression of a functional pyruvate dehydrogenase complex in the cytosol.

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