scholarly journals Tight Coupling of Partial Reactions in the Acetyl-CoA Decarbonylase/Synthase (ACDS) Multienzyme Complex from Methanosarcina thermophila

2010 ◽  
Vol 285 (20) ◽  
pp. 15450-15463 ◽  
Author(s):  
Simonida Gencic ◽  
Evert C. Duin ◽  
David A. Grahame
Keyword(s):  
Multienzyme Complex ◽  
Tight Coupling ◽  
Acetyl Coa ◽  
Methanosarcina Thermophila

scholarly journals A Multienzyme Complex Channels Substrates and Electrons through Acetyl-CoA and Methane Biosynthesis Pathways in Methanosarcina

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e107563 ◽  
Author(s):  
Dillon J. Lieber ◽  
Jennifer Catlett ◽  
Nandu Madayiputhiya ◽  
Renu Nandakumar ◽  
Madeline M. Lopez ◽  
...  
Keyword(s):  
Multienzyme Complex ◽  
Acetyl Coa

scholarly journals Kinetic studies of the fatty acid synthetase multienzyme complex from Euglena gracilis variety bacillaris

1981 ◽  
Vol 199 (2) ◽  
pp. 383-392 ◽  
Author(s):  
T A Walker ◽  
Z L Jonak ◽  
L M S Worsham ◽  
M L Ernst-Fonberg
Keyword(s):  
Fatty Acid ◽  
Euglena Gracilis ◽  
Substrate Inhibition ◽  
Fatty Acid Synthetase ◽  
Synthetase Activity ◽  
Multienzyme Complex ◽  
Acetyl Coa ◽  
Malonyl Coa ◽  
Ping Pong ◽  
Wide Range

A fatty acid synthetase multienzyme complex was purified from Euglena gracilis variety bacillaris. The fatty acid synthetase activity is specifically inhibited by antibodies against Escherichia coli acyl-carrier protein. The Euglena enzyme system requires both NADPH and NADH for maximal activity. An analysis was done of the steady-state kinetics of the reaction catalysed by the fatty acid synthetase multienzyme complex. Initial-velocity studies were done in which the concentrations of the following pairs of substrates were varied: malonyl-CoA and acetyl-CoA, NADPH and acetyl-CoA, malonyl-CoA and NADPH. In all three cases patterns of the Ping Pong type were obtained. Product-inhibition studies were done with NADP+ and CoA. NADP+ is a competitive inhibitor with respect to NADPH, and uncompetitive with respect to malonyl-CoA and acetyl-CoA. CoA is uncompetitive with respect to NADPH and competitive with respect to malonyl-CoA and acetyl-CoA. When the concentrations of acetyl-CoA and malonyl-CoA were varied over a wide range, mutual competitive substrate inhibition was observed. When the fatty acid synthetase was incubated with radiolabelled acetyl-CoA or malonyl-CoA, labelled acyl-enzyme was isolated. The results are consistent with the idea that fatty acid synthesis proceeds by a multisite substituted-enzyme mechanism involving Ping Pong reactions at the following enzyme sites: acetyl transacylase, malonyl transacylase, beta-oxo acyl-enzyme synthetase and fatty acyl transacylase.

scholarly journals Adaptations in Protein Expression and Regulated Activity of Pyruvate Dehydrogenase Multienzyme Complex in Human Systolic Heart Failure

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Freya L. Sheeran ◽  
Julie Angerosa ◽  
Norman Y. Liaw ◽  
Michael M. Cheung ◽  
Salvatore Pepe
Keyword(s):  
Heart Failure ◽  
Pyruvate Dehydrogenase ◽  
Critical Role ◽  
Systolic Heart Failure ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Multienzyme Complex ◽  
Acetyl Coa ◽  
Altered Expression ◽  
End Stage

Pyruvate dehydrogenase (PDH) complex, a multienzyme complex at the nexus of glycolytic and Krebs cycles, provides acetyl-CoA to the Krebs cycle and NADH to complex I thus supporting a critical role in mitochondrial energy production and cellular survival. PDH activity is regulated by pyruvate dehydrogenase phosphatases (PDP1, PDP2), pyruvate dehydrogenase kinases (PDK 1-4), and mitochondrial pyruvate carriers (MPC1, MPC2). As NADH-dependent oxidative phosphorylation is diminished in systolic heart failure, we tested whether the left ventricular myocardium (LV) from end-stage systolic adult heart failure patients (n=26) exhibits altered expression of PDH complex subunits, PDK, MPC, PDP, and PDH complex activity, compared to LV from nonfailing donor hearts (n=21). Compared to nonfailing LV, PDH activity and relative expression levels of E2, E3bp, E1α, and E1βsubunits were greater in LV failure. PDK4, MPC1, and MPC2 expressions were decreased in failing LV, whereas PDP1, PDP2, PDK1, and PDK2 expressions did not differ between nonfailing and failing LV. In order to examine PDK4 further, donor human LV cardiomyocytes were induced in culture to hypertrophy with 0.1 μM angiotensin II and treated with PDK inhibitors (0.2 mM dichloroacetate, or 5 mM pyruvate) or activators (0.6 mM NADH plus 50 μM acetyl CoA). In isolated hypertrophic cardiomyocytesin vitro, PDK activators and inhibitors increased and decreased PDK4, respectively. In conclusion, in end-stage failing hearts, greater expression of PDH proteins and decreased expression of PDK4, MPC1, and MPC2 were evident with higher rates of PDH activity. These adaptations support sustained capacity for PDH to facilitate glucose metabolism in the face of other failing bioenergetic pathways.

scholarly journals Intermediates in fatty acid oxidation

1973 ◽  
Vol 132 (1) ◽  
pp. 61-76 ◽  
Author(s):  
H. B. Stewart ◽  
P. K. Tubbs ◽  
K. K. Stanley
Keyword(s):  
Liver Mitochondria ◽  
Fatty Acyl ◽  
Acid Oxidation ◽  
Aqueous Extracts ◽  
Multienzyme Complex ◽  
Acetyl Coa ◽  
Kidney Mitochondria ◽  
Liver And Kidney ◽  
Phenazine Methosulphate ◽  
Derivatives Of

1. Aqueous extracts of acetone-dried liver and kidney mitochondria, supplemented with NAD+, CoA and phenazine methosulphate, efficiently convert fatty-acyl-CoA compounds into acetyl-CoA; the process was followed with an O2 electrode. 2. Label from [1-14C]octanoyl-CoA appears in acetyl-CoA more rapidly than that from [8-14C]octanoyl-CoA. 3. Oxidation of [8-14C]octanoyl-CoA was terminated by addition of neutral ethanolic hydroxylamine and the resulting hydroxamates were separated chromatographically. Hydroxamate derivatives of 3-hydroxyoctanoyl-, hexanoyl-, butyryl- and acetyl-CoA were obtained. 4. These and other observations suggest that oxidation of octanoyl-CoA by extracts involves participation of free intermediates rather than uninterrupted complete degradation of individual molecules to acetyl-CoA by a multienzyme complex. 5. Intact liver mitochondria studied by the hydroxamate technique were also shown to form intermediates during oxidation of labelled octanoates. In addition to octanoylhydroxamate, [8-14C]octanoate gave rise to small amounts of hexanoyl-, butyryl- and 3-hydroxyoctanoyl-hydroxamate. In contrast with extracts, however, where the quantity of intermediates found was a significant fraction of the precursors, mitochondria oxidizing octanoate contained much larger quantities of octanoyl-CoA than of any other intermediate.

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