Control of lipid oxidation at the mitochondrial levelThis paper article is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

2009 ◽  
Vol 34 (3) ◽  
pp. 382-388 ◽  
Author(s):  
Kent Sahlin
Keyword(s):  
Lipid Oxidation ◽  
Feedback Inhibition ◽  
Peer Review Process ◽  
Energy State ◽  
Tricarboxylic Acid Cycle ◽  
Low Energy ◽  
Acetyl Coa ◽  
Intensive Exercise ◽  
Transport Chain ◽  
Electron Carriers

The rate of lipid oxidation during exercise is controlled at several sites, and there is a reciprocal dependency between oxidation of lipids and carbohydrates (CHO). It is well known that the proportion of the 2 fuels oxidized is influenced by substrate availability and exercise intensity, but the mechanisms regulating fuel preferences remain unclear. During intense exercise, oxidation of long-chain fatty acids (LCFAs) decreases, and the major control is likely to be at the mitochondrial level. Potential mitochondrial sites for control of lipid oxidation include transport of LCFAs into mitochondrial matrix, β-oxidation, the tricarboxylic acid cycle, and the electron transport chain (ETC). CHO catabolism may impair lipid oxidation by interfering with the transfer of LCFAs into mitochondria and by competing for mutual cofactors (i.e., nicotinamide adenine dinucleotide and (or) coenzyme A (CoA)). The different effect of energy state on the catabolism of CHO and lipids is likely to be of major importance in explaining the shift in fuel utilization during intensive exercise. Formation of acetyl-CoA from CHO is activated by a low energy state, and will lead to accumulation of products that are inhibitory to lipid oxidation. In contrast, β-oxidation of LCFAs to acetyl-CoA is not stimulated by a low energy state. Further interaction between CHO and LCFAs may occur by substrate competition for electron carriers at ETC, due to provisions of electrons through different complexes. Feedback inhibition of β-oxidation by redox state is thought to be an important mechanism for the slowing of lipid oxidation during intensive exercise.

scholarly journals Factors affecting the activity of citrate synthase of Acetobacter xylinum and its possible regulatory role

1976 ◽  
Vol 153 (2) ◽  
pp. 173-179 ◽  
Author(s):  
M Swissa ◽  
M Benziman
Keyword(s):  
Citrate Synthase ◽  
Energy State ◽  
Tricarboxylic Acid Cycle ◽  
Energy Charge ◽  
Reaction Rates ◽  
Tricarboxylic Acid ◽  
Acetobacter Xylinum ◽  
Acetyl Coa ◽  
Acid Cycle

The citrate synthase activity of Acetobacter xylinum cells grown on glucose was the same as of cells grown on intermediates of the tricarboxylic acid cycle. The activity of citrate synthase in extracts is compatible with the overall rate of acetate oxidation in vivo. The enzyme was purified 47-fold from sonic extracts and its molecular weight was determined to be 280000 by gel filtration. It has an optimum activity at pH 8.4. Reaction rates with the purified enzyme were hyperbolic functions of both acetyl-CoA and oxaloacetate. The Km for acetyl-CoA is 18 μm and that for oxaloacetate 8.7 μm. The enzyme is inhibited by ATP according to classical kinetic patterns. This inhibition is competitive with respect to acetyl-CoA (Ki = 0.9 mM) and non-competitive with respect to oxaloacetate. It is not affected by changes in pH and ionic strength and is not relieved by an excess of Mg2+ ions. Unlike other Gram-negative bacteria, the A. xylinum enzyme is not inhibited by NADH, but is inhibited by high concentrations of NADPH. The activity of the enzyme varies with energy charge in a manner consistent with its role in energy metabolism. It is suggested that the flux through the tricarboxylic acid cycle in A. xylinum is regulated by modulation of citrate synthase activity in response to the energy state of the cells.

scholarly journals The Impact of Acetyl-CoA and Aspartate Shortages on the N-Acetylaspartate Level in Different Models of Cholinergic Neurons

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 522 ◽  
Author(s):  
Marlena Zyśk ◽  
Monika Sakowicz-Burkiewicz ◽  
Piotr Pikul ◽  
Robert Kowalski ◽  
Anna Michno ◽  
...  
Keyword(s):  
Direct Evidence ◽  
Tricarboxylic Acid Cycle ◽  
Cholinergic Neurons ◽  
Tricarboxylic Acid ◽  
Acetyl Coa ◽  
Male Adult ◽  
Acid Cycle ◽  
Transport Chain ◽  
The Impact ◽  
Malate Aspartate Shuttle

N-acetylaspartate is produced by neuronal aspartate N-acetyltransferase (NAT8L) from acetyl-CoA and aspartate. In cholinergic neurons, acetyl-CoA is also utilized in the mitochondrial tricarboxylic acid cycle and in acetylcholine production pathways. While aspartate has to be shared with the malate–aspartate shuttle, another mitochondrial machinery together with the tricarboxylic acid cycle supports the electron transport chain turnover. The main goal of this study was to establish the impact of toxic conditions on N-acetylaspartate production. SN56 cholinergic cells were exposed to either Zn2+ overload or Ca2+ homeostasis dysregulation and male adult Wistar rats’ brains were studied after 2 weeks of challenge with streptozotocin-induced hyperglycemia or daily theophylline treatment. Our results allow us to hypothesize that the cholinergic neurons from brain septum prioritized the acetylcholine over N-acetylaspartate production. This report provides the first direct evidence for Zn2+-dependent suppression of N-acetylaspartate synthesis leading to mitochondrial acetyl-CoA and aspartate shortages. Furthermore, Zn2+ is a direct concentration-dependent inhibitor of NAT8L activity, while Zn2+-triggered oxidative stress is unlikely to be significant in such suppression.

13C isotopomer model for estimation of anaplerotic substrate oxidation via acetyl-CoA

1996 ◽  
Vol 271 (4) ◽  
pp. E788-E799 ◽  
Author(s):  
F. M. Jeffrey ◽  
C. J. Storey ◽  
A. D. Sherry ◽  
C. R. Malloy
Keyword(s):  
Biochemical Analysis ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Acetyl Coa ◽  
Acid Cycle ◽  
Propionate Metabolism ◽  
13C Nuclear Magnetic Resonance ◽  
Isotopomer Analysis ◽  
Tricarboxylic Acid Cycle Intermediates ◽  
Anaplerotic Pathway

A previous model using 13C nuclear magnetic resonance isotopomer analysis provided for direct measurement of the oxidation of 13C-enriched substrates in the tricarboxylic acid cycle and/or their entry via anaplerotic pathways. This model did not allow for recycling of labeled metabolites from tricarboxylic acid cycle intermediates into the acetyl-CoA pool. An extension of this model is now presented that incorporates carbon flow from oxaloacetate or malate to acetyl-CoA. This model was examined using propionate metabolism in the heart, in which previous observations indicated that all of the propionate consumed was oxidized to CO2 and water. Application of the new isotopomer model shows that 2 mM [3-13C]propionate entered the tricarboxylic acid cycle as succinyl-CoA (an anaplerotic pathway) at a rate equal to 52% of tricarboxylic acid cycle turnover and that all of this carbon entered the acetyl-CoA pool and was oxidized. This was verified using standard biochemical analysis; from the rate (mumol.min-1.g dry wt-1) of propionate uptake (4.0 +/- 0.7), the estimated oxygen consumption (24.8 +/- 5) matched that experimentally determined (24.4 +/- 3).

scholarly journals Effects of L-Malate on Mitochondrial Oxidoreductases in Liver of Aged Rats

2011 ◽  
pp. 329-336 ◽  
Author(s):  
J.-L. WU ◽  
Q.-P. WU ◽  
Y.-P. PENG ◽  
J.-M. ZHANG
Keyword(s):  
Electron Transport ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Electron Transport Chain ◽  
Nadh Dehydrogenase ◽  
Tricarboxylic Acid Cycle ◽  
Radical Scavenger ◽  
Aged Rats ◽  
Transport Chain ◽  
Nadh Cytochrome

Accumulation of oxidative damage has been implicated to be a major causative factor in the decline in physiological functions that occur during the aging process. The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS), considered as the pathogenic agent of many diseases and aging. L-malate, a tricarboxylic acid cycle intermediate, plays an important role in transporting NADH from cytosol to mitochondria for energy production. Previous studies in our laboratory reported L-malate as a free radical scavenger in aged rats. In the present study we focused on the effect of L-malate on the activities of electron transport chain in young and aged rats. We found that mitochondrial membrane potential (MMP) and the activities of succinate dehydrogenase, NADH-cytochrome c oxidoreductase and cytochrome c oxidase in liver of aged rats were significantly decreased when compared to young control rats. Supplementation of L-malate to aged rats for 30 days slightly increased MMP and improved the activities of NADH-dehydrogenase, NADH-cytochrome c oxidoreductase and cytochrome c oxidase in liver of aged rats when compared with aged control rats. In young rats, L-malate administration increased only the activity of NADH-dehydrogenase. Our result suggested that L-malate could improve the activities of electron transport chain enzymes in aged rats

scholarly journals Association of the malate dehydrogenase-citrate synthase metabolon is modulated by intermediates of the Krebs tricarboxylic acid cycle

2021 ◽  
Author(s):  
Joy Omini ◽  
Izabela Wojciechowska ◽  
Aleksandra Skirycz ◽  
Hideaki Moriyama ◽  
Toshihiro Obata
Keyword(s):  
Malate Dehydrogenase ◽  
Metabolic Flux ◽  
Citrate Synthase ◽  
Tricarboxylic Acid Cycle ◽  
Feedback Regulation ◽  
Dynamic Structure ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Enzyme Complex ◽  
Acetyl Coa

Mitochondrial malate dehydrogenase (MDH)-citrate synthase (CS) multi-enzyme complex is a part of the Krebs tricarboxylic acid (TCA) cycle 'metabolon' which is enzyme machinery catalyzing sequential reactions without diffusion of reaction intermediates into a bulk matrix. This complex is assumed to be a dynamic structure involved in the regulation of the cycle by enhancing metabolic flux. Microscale Thermophoresis analysis of the porcine heart MDH-CS complex revealed that substrates of the MDH and CS reactions, NAD+ and acetyl-CoA, enhance complex association while products of the reactions, NADH and citrate, weaken the affinity of the complex. Oxaloacetate enhanced the interaction only when it was presented together with acetyl-CoA. Structural modeling using published CS structures suggested that the binding of these substrates can stabilize the closed format of CS which favors the MDH-CS association. Two other TCA cycle intermediates, ATP, and low pH also enhanced the association of the complex. These results suggest that dynamic formation of the MDH-CS multi-enzyme complex is modulated by metabolic factors responding to respiratory metabolism, and it may function in the feedback regulation of the cycle and adjacent metabolic pathways.

scholarly journals Trivial low energy states for commuting Hamiltonians, and the quantum PCP conjecture

2013 ◽  
Vol 13 (5&6) ◽  
pp. 393-429
Author(s):  
Matthew Hastings
Keyword(s):  
Ground State ◽  
Coding Theory ◽  
Energy State ◽  
Ground States ◽  
Coarse Graining ◽  
Quantum Circuit ◽  
Technical Condition ◽  
Two Dimensions ◽  
Low Energy ◽  
Coarse Grained

We consider the entanglement properties of ground states of Hamiltonians which are sums of commuting projectors (we call these commuting projector Hamiltonians), in particular whether or not they have ``trivial" ground states, where a state is trivial if it is constructed by a local quantum circuit of bounded depth and range acting on a product state. It is known that Hamiltonians such as the toric code only have nontrivial ground states in two dimensions. Conversely, commuting projector Hamiltonians which are sums of two-body interactions have trivial ground states\cite{bv}. Using a coarse-graining procedure, this implies that any such Hamiltonian with bounded range interactions in one dimension has a trivial ground state. In this paper, we further explore the question of which Hamiltonians have trivial ground states. We define an ``interaction complex" for a Hamiltonian, which generalizes the notion of interaction graph and we show that if the interaction complex can be continuously mapped to a $1$-complex using a map with bounded diameter of pre-images then the Hamiltonian has a trivial ground state assuming one technical condition on the Hamiltonians holds (this condition holds for all stabilizer Hamiltonians, and we additionally prove the result for all Hamiltonians under one assumption on the $1$-complex). While this includes the cases considered by Ref.~\onlinecite{bv}, we show that it also includes a larger class of Hamiltonians whose interaction complexes cannot be coarse-grained into the case of Ref.~\onlinecite{bv} but still can be mapped continuously to a $1$-complex. One motivation for this study is an approach to the quantum PCP conjecture. We note that many commonly studied interaction complexes can be mapped to a $1$-complex after removing a small fraction of sites. For commuting projector Hamiltonians on such complexes, in order to find low energy trivial states for the original Hamiltonian, it would suffice to find trivial ground states for the Hamiltonian with those sites removed. Such trivial states can act as a classical witness to the existence of a low energy state. While this result applies for commuting Hamiltonians and does not necessarily apply to other Hamiltonians, it suggests that to prove a quantum PCP conjecture for commuting Hamiltonians, it is worth investigating interaction complexes which cannot be mapped to $1$-complexes after removing a small fraction of points. We define this more precisely below; in some sense this generalizes the notion of an expander graph. Surprisingly, such complexes do exist as will be shown elsewhere\cite{fh}, and have useful properties in quantum coding theory.

scholarly journals Genome of Methylobacillus flagellatus, Molecular Basis for Obligate Methylotrophy, and Polyphyletic Origin of Methylotrophy

2007 ◽  
Vol 189 (11) ◽  
pp. 4020-4027 ◽  
Author(s):  
Ludmila Chistoserdova ◽  
Alla Lapidus ◽  
Cliff Han ◽  
Lynne Goodwin ◽  
Liz Saunders ◽  
...  
Keyword(s):  
Formate Dehydrogenase ◽  
Tricarboxylic Acid Cycle ◽  
Methylococcus Capsulatus ◽  
Methylobacterium Extorquens ◽  
Circular Chromosome ◽  
Transport Chain ◽  
Carbon Compounds ◽  
Formaldehyde Oxidation ◽  
Global Carbon ◽  
Single Circular Chromosome

ABSTRACT Along with methane, methanol and methylated amines represent important biogenic atmospheric constituents; thus, not only methanotrophs but also nonmethanotrophic methylotrophs play a significant role in global carbon cycling. The complete genome of a model obligate methanol and methylamine utilizer, Methylobacillus flagellatus (strain KT) was sequenced. The genome is represented by a single circular chromosome of approximately 3 Mbp, potentially encoding a total of 2,766 proteins. Based on genome analysis as well as the results from previous genetic and mutational analyses, methylotrophy is enabled by methanol and methylamine dehydrogenases and their specific electron transport chain components, the tetrahydromethanopterin-linked formaldehyde oxidation pathway and the assimilatory and dissimilatory ribulose monophosphate cycles, and by a formate dehydrogenase. Some of the methylotrophy genes are present in more than one (identical or nonidentical) copy. The obligate dependence on single-carbon compounds appears to be due to the incomplete tricarboxylic acid cycle, as no genes potentially encoding alpha-ketoglutarate, malate, or succinate dehydrogenases are identifiable. The genome of M. flagellatus was compared in terms of methylotrophy functions to the previously sequenced genomes of three methylotrophs, Methylobacterium extorquens (an alphaproteobacterium, 7 Mbp), Methylibium petroleiphilum (a betaproteobacterium, 4 Mbp), and Methylococcus capsulatus (a gammaproteobacterium, 3.3 Mbp). Strikingly, metabolically and/or phylogenetically, the methylotrophy functions in M. flagellatus were more similar to those in M. capsulatus and M. extorquens than to the ones in the more closely related M. petroleiphilum species, providing the first genomic evidence for the polyphyletic origin of methylotrophy in Betaproteobacteria.

Electron Transport to Assimilatory Nitrate Reductase in A zotobacter vinelandii

1981 ◽  
Vol 36 (11-12) ◽  
pp. 1030-1035 ◽  
Author(s):  
Hermann Bothe ◽  
Klaus-Peter Häger
Keyword(s):  
Electron Transport ◽  
Nitrate Reductase ◽  
Nitrate Reduction ◽  
Azotobacter Vinelandii ◽  
Additive Effects ◽  
Electron Carrier ◽  
Transport Chain ◽  
Solubilized Enzyme ◽  
Electron Carriers ◽  
Bound Electron

Abstract Assimilatory nitrate reductase was particle-bound in extracts from Azotobacter vinelandii. Nitrate reduction by particle fractions was dependent on NADPH and a particle-bound electron carrier. When the enzyme was solubilized from the particles by treatment with detergents, the particle-bound electron carrier could be substituted by ferredoxin or flavodoxin. Flavodoxin reduced at the expense of photoreduced deazaflavin was much more efficient than ferredoxin in transferring electrons to nitrate reductase. The addition of both ferredoxin and flavodoxin to the assays with photoreduced deazaflavin gave additive effects. With the solubilized enzyme, NADPH only poorly supported nitrate reduction even after the addition of electron carriers. The experiments indicate that A. vinelandii utilizes an electron transport chain between NADPH and nitrate reductase with some properties similar to those described for the generation of reductants to nitrogenase.

scholarly journals Highly Excited Molecular Hydrogen in Orion

1989 ◽  
Vol 120 ◽  
pp. 323-326
Author(s):  
Hans H. Hippelein ◽  
Guido Münch
Keyword(s):  
Molecular Hydrogen ◽  
Rotational Temperature ◽  
Energy State ◽  
Low Energy ◽  
Line Of Sight ◽  
Temperature Measuring ◽  
Molecule Formation ◽  
J 13 ◽  
Excitation Mechanisms

Observations of H2 lines in the IR have been mostly restricted to those with upper levels of low energy, which can be excited either collisionally in shocks or radiatively by UV starlight. In order to discriminate between the two excitation mechanisms we have measured in 11 μm range lines of the v=2-0 band arising from high rotational levels J≤;13. Their intensities, together with those of the IR lines, allow an estimate of the line of sight effective extinction and a determination of the rotational temperature measuring their joint degree of excitation. The latter parameter provides information about the energy state of the molecules at their formation and ejection from grain surfaces and thus constrains the hypothetical models for H2 molecule formation.

scholarly journals The Antialgal Mechanism of Luteolin-7-O-Glucuronide on Phaeocystis globosa by Metabolomics Analysis

2019 ◽  
Vol 16 (17) ◽  
pp. 3222
Author(s):  
Jingyi Zhu ◽  
Yeyin Yang ◽  
Shunshan Duan ◽  
Dong Sun
Keyword(s):  
Harmful Algal Blooms ◽  
Algal Blooms ◽  
Tricarboxylic Acid Cycle ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Phaeocystis Globosa ◽  
Acetyl Coa ◽  
Intracellular Metabolites ◽  
Extracellular Metabolites ◽  
Significant Difference

Antialgal compounds from plants have been identified as promising candidates for controlling harmful algal blooms (HABs). In our previous study, luteolin-7-O-glucuronide was used as a promising algistatic agent to control Phaeocystis globosa (P. globose) blooms; however, its antialgal mechanism on P. globosa have not yet been elaborated in detail. In this study, a liquid chromatography linked to tandem mass spectrometry (LC-MS/MS)-based untargeted metabolomic approach was used to investigate changes in intracellular and extracellular metabolites of P. globosa after exposure to luteolin-7-O-glucuronide. Significant differences in intracellular metabolites profiles were observed between treated and untreated groups; nevertheless, metabolic statuses for extracellular metabolites were similar among these two groups. For intracellular metabolites, 20 identified metabolites showed significant difference. The contents of luteolin, gallic acid, betaine and three fatty acids were increased, while the contents of α-Ketoglutarate and acetyl-CoA involved in tricarboxylic acid cycle, glutamate, and 11 organic acids were decreased. Changes in those metabolites may be induced by the antialgal compound in response to stress. The results revealed that luteolin played a vital role in the antialgal mechanism of luteolin-7-O-glucuronide on P. globosa, because luteolin increased the most in the treatment groups and had strong antialgal activity on P. globosa. α-Ketoglutarate and acetyl-CoA were the most inhibited metabolites, indicating that the antialgal compound inhibited the growth through disturbed the tricarboxylic acid (TCA) cycle of algal cells. To summarize, our data provides insights into the antialgal mechanism of luteolin-7-O-glucuronide on P. globosa, which can be used to further control P. globosa blooms.

Sign in / Sign up

Export Citation Format

Share Document