scholarly journals Glucose feeds the TCA cycle via environmental ethanol in fermenting yeast

Author(s):  
Tianxia Xiao ◽  
Artem Khan ◽  
Yihui Shen ◽  
Li Chen ◽  
Joshua Rabinowitz

Abstract Ethanol and lactate are typical waste products of glucose fermentation. In mammals, glucose is catabolized by glycolysis into circulating lactate, which is broadly used throughout the body as a carbohydrate fuel. Individual cells can both uptake and excrete lactate, uncoupling glycolysis from glucose oxidation. Here we show that similar uncoupling occurs in the yeast Saccharomyces cerevisiae. Even in fermenting yeast that are net releasing ethanol, media 13C-ethanol rapid enters and is oxidized to acetaldehyde and acetyl-CoA. This is evident in exogenous ethanol being a major source of both cytosolic and mitochondrial acetyl units. 2H-tracing reveals that ethanol is also a major source of both NADH and NADPH, and this role is augmented under oxidative stress conditions. Thus, uncoupling of glycolysis from the oxidation of glucose-derived carbon via rapid reversible reactions is an ancient and conserved feature of eukaryotic metabolism.

1995 ◽  
Vol 268 (6) ◽  
pp. G879-G888 ◽  
Author(s):  
C. E. Kight ◽  
S. E. Fleming

The influence of glutamine on glucose oxidation was assessed in epithelial cells isolated from the mucosa of the proximal, mid-, and distal small intestine of young, fed, male rats. Glucose oxidation declined along the length of the small intestine, with values from the mid- and distal segments representing approximately 55% and 40%, respectively, of the value from the proximal segment. A gradient along the small intestine was noted also in the influence of glutamine on glucose oxidation: glutamine suppressed glucose oxidation approximately 60% in the proximal small intestine, 39% in the mid-intestine, and 31% in the distal small intestine. Glutamine suppressed the oxidation of glucose carbon that entered the tricarboxylic acid (TCA) cycle; this was determined using CO2 ratios derived from acetate and glucose isotopes. In cells from the proximal segment, the probability that carbon entering the cycle would complete one full turn was reduced by glutamine from 0.77 to 0.28. The entry of glucose-derived pyruvate into the TCA cycle did not appear to be influenced by the presence of glutamine, however. Glutamine had no influence on the proportion of glucose metabolism that occurred via the pentose phosphate pathway (which averaged 5% or less), but reduced flux of carbon through pyruvate carboxylase relative to flux through pyruvate dehydrogenase from 40% to 9% in cells from the proximal segment. These data suggest that, in the presence of glutamine, the fate of pyruvate carbon (derived from glucose or elsewhere) entering the TCA cycle is altered from that of oxidation to anaplerosis and subsequent efflux of TCA cycle intermediates into newly synthesized compounds.


2020 ◽  
Author(s):  
Riccardo Mobili ◽  
Sonia La Cognata ◽  
Francesca Merlo ◽  
Andrea Speltini ◽  
Massimo Boiocchi ◽  
...  

<div> <p>The extraction of the succinate dianion from a neutral aqueous solution into dichloromethane is obtained using a lipophilic cage-like dicopper(II) complex as the extractant. The quantitative extraction exploits the high affinity of the succinate anion for the cavity of the azacryptate. The anion is effectively transferred from the aqueous phase, buffered at pH 7 with HEPES, into dichloromethane. A 1:1 extractant:anion adduct is obtained. Extraction can be easily monitored by following changes in the UV-visible spectrum of the dicopper complex in dichloromethane, and by measuring the residual concentration of succinate in the aqueous phase by HPLC−UV. Considering i) the relevance of polycarboxylates in biochemistry, as e.g. normal intermediates of the TCA cycle, ii) the relevance of dicarboxylates in the environmental field, as e.g. waste products of industrial processes, and iii) the recently discovered role of succinate and other dicarboxylates in pathophysiological processes including cancer, our results open new perspectives for research in all contexts where selective recognition, trapping and extraction of polycarboxylates is required. </p> </div>


Author(s):  
Riccardo Mobili ◽  
Sonia La Cognata ◽  
Francesca Merlo ◽  
Andrea Speltini ◽  
Massimo Boiocchi ◽  
...  

<div> <p>The extraction of the succinate dianion from a neutral aqueous solution into dichloromethane is obtained using a lipophilic cage-like dicopper(II) complex as the extractant. The quantitative extraction exploits the high affinity of the succinate anion for the cavity of the azacryptate. The anion is effectively transferred from the aqueous phase, buffered at pH 7 with HEPES, into dichloromethane. A 1:1 extractant:anion adduct is obtained. Extraction can be easily monitored by following changes in the UV-visible spectrum of the dicopper complex in dichloromethane, and by measuring the residual concentration of succinate in the aqueous phase by HPLC−UV. Considering i) the relevance of polycarboxylates in biochemistry, as e.g. normal intermediates of the TCA cycle, ii) the relevance of dicarboxylates in the environmental field, as e.g. waste products of industrial processes, and iii) the recently discovered role of succinate and other dicarboxylates in pathophysiological processes including cancer, our results open new perspectives for research in all contexts where selective recognition, trapping and extraction of polycarboxylates is required. </p> </div>


1994 ◽  
Vol 72 (3) ◽  
pp. 266-274 ◽  
Author(s):  
S. E. Fleming ◽  
C. E. Kight

The influence of aging on glucose and glutamine metabolism by isolated jejunal cells was studied using young (4 months) and aged (24 months) Fischer 344 male rats when fed ad libitum or fasted 48 h. Concentration-dependent oxidation of glucose ([14C(U)]glucose) followed Michaelis–Menten kinetics. Neither Kox nor Vmax was influenced by animal age or feeding status, but at 1 mM, glucose oxidation was significantly higher for aged than young fed animals. In all animal groups, glutamine reduced glucose oxidation by ca. 60%, glucose stimulated glutamine oxidation by ca. 25%, and succinate CO2 ratios ranged from 1.37 for 20 mM glucose to 5.46 for 20 mM glucose + glutamine. The probability that a substrate that enters the TCA cycle will either remain in the cycle for one complete turn or leave and reenter as acetyl-CoA averaged 0.85 for glucose, 0.36 for glutamine, and 0.31 for glucose + glutamine. In comparison with the young fed animals, cells from fed aged animals showed lower oxygen uptake in the absence and presence of exogenous substrate, lower glucose oxidation, lower entry of glucose and glutamine into the TCA cycle, and lower contribution of glucose and glutamine carbon to anaplerosis and subsequent synthetic compounds. Differences between the young and aged animals were more pronounced in cells from fed animals than from fasted animals.Key words: glucose, glutamine, fasting, oxidation, anaplerosis.


2003 ◽  
Vol 95 (2) ◽  
pp. 477-482 ◽  
Author(s):  
J. Ruzzin ◽  
F. Péronnet ◽  
J. Tremblay ◽  
D. Massicotte ◽  
C. Lavoie

The purpose of the present experiment was to compare 13CO2 recovery at the mouth, and the corresponding exogenous glucose oxidation computed, during a 100-min exercise at 63 ± 3% maximal O2 uptake with ingestion of glucose (1.75 g/kg) in six active male subjects, by use of [U-13C] and [1,2-13C]glucose. We hypothesized that 13C recovery and exogenous glucose oxidation could be lower with [1,2-13C] than [U-13C]glucose because both tracers provide [13C]acetate, with possible loss of 13C in the tricarboxylic acid (TCA) cycle, but decarboxylation of pyruvate from [U-13C]glucose also provides 13CO2, which is entirely recovered at the mouth during exercise. The recovery of 13C (25.8 ± 2.3 and 27.4 ± 1.2% over the exercise period) and the amounts of exogenous glucose oxidized computed were not significantly different with [1,2-13C] and [U-13C]glucose (28.9 ± 2.6 and 30.7 ± 1.3 g, between minutes 40 and 100), suggesting that no significant loss of 13C occurred in the TCA cycle. This stems from the fact that, during exercise, the rate of exogenous glucose oxidation is probably much larger than the flux of the metabolic pathways fueled from TCA cycle intermediates. It is thus unlikely that a significant portion of the 13C entering the TCA cycle could be diverted to these pathways. From a methodological standpoint, this result indicates that when a large amount of [13C]glucose is ingested and oxidized during exercise, 13CO2 production at the mouth accurately reflects the rate of glucose entry in the TCA cycle and that no correction factor is needed to compute the oxidative flux of exogenous glucose.


Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 406
Author(s):  
Ernesto Martínez-Martínez ◽  
Francisco Souza-Neto ◽  
Sara Jiménez-González ◽  
Victoria Cachofeiro

The vascular system plays a central role in the transport of cells, oxygen and nutrients between different regions of the body, depending on the needs, as well as of metabolic waste products for their elimination. While the structure of different components of the vascular system varies, these structures, especially those of main arteries and arterioles, can be affected by the presence of different cardiovascular risk factors, including obesity. This vascular remodeling is mainly characterized by a thickening of the media layer as a consequence of changes in smooth muscle cells or excessive fibrosis accumulation. These vascular changes associated with obesity can trigger functional alterations, with endothelial dysfunction and vascular stiffness being especially common features of obese vessels. These changes can also lead to impaired tissue perfusion that may affect multiple tissues and organs. In this review, we focus on the role played by perivascular adipose tissue, the activation of the renin-angiotensin-aldosterone system and endoplasmic reticulum stress in the vascular dysfunction associated with obesity. In addition, the participation of oxidative stress in this vascular damage, which can be produced in the perivascular adipose tissue as well as in other components of the vascular wall, is updated.


1958 ◽  
Vol 4 (3) ◽  
pp. 205-213 ◽  
Author(s):  
John H. Litchfield ◽  
Z. John Ordal

The oxidative metabolism of Rhodolorula gracilis NRRL Y-1091 was investigated. Data was presented showing the oxidation of glucose, acetate, pyruvate, xylose, D- and L-arabinose, by both glucose- and xylose-grown cells. Gluconate was oxidized by the glucose-grown cells, while ribose was oxidized by the xylose-grown cells. Cell-free extracts of glucose-grown cells oxidized glucose, gluconate, glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-diphosphate, and ribose-5-phosphate. Pentose phosphate was demonstrated as a product of glucose-6-phosphate oxidation. Resting-cell suspensions were unable to oxidize citrate, but they oxidized the dicarboxylic acids of the TCA cycle. Citrate was detected as a product of the oxidation of acetate, pyruvate, and malate in the presence of fluoroacetate. Cell-free extracts of glucose-grown cells oxidized citrate, isocitrate, and the dicarboxylic acids of the TCA cycle.


1995 ◽  
Vol 268 (2) ◽  
pp. H713-H719 ◽  
Author(s):  
J. T. Barron ◽  
J. E. Parrillo

Vascular smooth muscle metabolism is characterized by substantial production of lactic acid even under fully oxygenated conditions. The role the aerobic production of lactate plays in the energetics of smooth muscle is obscure and was investigated in this study. Helical strips of porcine carotid arteries were incubated in medium containing 1 mM dichloroacetate (DCA), an agent that stimulates pyruvate dehydrogenase and promotes the oxidation of glucose. Lactate production in resting muscle was decreased in the presence of DCA (0.033 +/- 0.006 vs. 0.111 +/- 0.014 mumol.g-1.min-1, P < 0.02), indicating diversion of glucose metabolism from lactate production to enhanced glucose oxidation. This was associated with reduction in the level of ATP+phosphocreatine (PCr) (0.99 +/- 0.01 vs. 1.40 +/- 0.09 mumol/g, P < 0.05) and cataplerosis of the tricarboxylic acid (TCA) cycle. Contraction by KCl was also associated with reduced lactate production in the presence of DCA (0.086 +/- 0.017 vs. 0.20 +/- 0.002 mumol.g-1.min-1, P < 0.01), but ATP+PCr normalized, and there was anaplerosis of the TCA cycle. Glycogen in control arteries declined by approximately 1.3 mumol/g over 30 min K+ contraction but was unchanged in the presence of DCA. By calculation, the glycogen spared could be accounted for by the quantity of glucose diverted from lactate production to glucose oxidation during contraction. It is concluded that the aerobic production of lactate is a mechanism affording optimal coordination and modulation of glucose supply and oxidative energy production with energy demand.


1982 ◽  
Vol 63 (6) ◽  
pp. 37-39
Author(s):  
T. N. Oparina

The state of aerobic oxidation of glucose was studied in 146 children with acute pneumonia and in 50 healthy children by determining the activity of lactate dehydrogenase, malate dehydrogenase and their isoenzymes, the content of pyruvic acid in the blood. It has been clinically established that with pneumonia there are violations of the contractility of the myocardium. Moreover, these disorders are in direct proportion to the depth of the shift in the ratio of aerobic and anaerobic processes in the body.


1981 ◽  
Vol 1 (10) ◽  
pp. 811-817 ◽  
Author(s):  
Michael J. Morgan ◽  
Kathleen M. Bowness ◽  
Pelin Faik

The metabolism of radioactively labelled D-glucose, L-glutamine, and L-glutamate has been determined in a glycolytic mutant of Chinese-hamster ovary cells, R1.1.7, and in its parent, CHO-K1. The complete oxidation of glucose via the TCA-cycle is negligible in both cell types, but there is significant oxidation of carbon-1. CHO-K1 cells derive most of their energy from glycolysis and are independent of respiration in the short term. R1.1.7 cells are respiration-dependent and are rapidly killed by respiratory inhibitors. Both cell types oxidize L-glutamine and L-glutamate, but the oxidation of these substrates does not appear sufficient to satisfy completely the energy requirements of R1.1.7 cells.


Sign in / Sign up

Export Citation Format

Share Document