scholarly journals Effects of insulin on the pattern of glucose metabolism in the perfused working and Lagendorff heart of normal and insulin-deficient rats

1969 ◽  
Vol 115 (3) ◽  
pp. 537-546 ◽  
Author(s):  
E B Chain ◽  
K. R. L. Mansford ◽  
L. H. Opie
Keyword(s):  
Glucose Metabolism ◽  
Tricarboxylic Acid Cycle ◽  
Work Load ◽  
Tricarboxylic Acid ◽  
Diaphragm Muscle ◽  
Perfusion Fluid ◽  
Acid Cycle ◽  
14Co2 Production ◽  
Tricarboxylic Acid Cycle Intermediates ◽  
Phosphorylated Sugars

1. The metabolic pattern of [U−14C]glucose in the isolated rat heart has been studied, with both retrograde aortic (Langendorff) and atrially (working) perfused preparations in the presence and absence of insulin, in normal animals, animals rendered insulin-deficient (by injection of anti-insulin serum 1hr. before excision of the heart) and animals rendered diabetic by streptozotocin injection 7 days before use. 2. Radioautochromatograms of heart extracts show that the pattern of glucose metabolism in heart muscle is more complex than in diaphragm muscle. In addition to 14CO2, glycogen, oligosaccharides, phosphorylated sugars and lactate (the main metabolites formed from [14C]glucose in diaphragm muscle), 14C label from [14C]glucose appears in heart muscle in glutamate, glutamine, aspartate and alanine, and in tricarboxylic acid-cycle intermediates. 3. By a quantitative scanning technique of two-dimensional chromatograms it was found that a mechanical work load stimulates glucose metabolism, increasing by a factor of 2–3 incorporation of 14C into all the metabolites mentioned above except lactate and phosphorylated sugars, into which 14C incorporation is in fact diminished; 14CO2 production is equally stimulated. 4. Addition of insulin to the perfusion fluid of the working heart causes increases in 14C incorporation, by a factor of about 1·5 into 14CO2, by a factor of about 3–5 into glycogen, lactate and phosphorylated sugars, by a factor of about 2–3 into glutamate and tricarboxylic acid-cycle intermediates and by a factor of about 0·5 into aspartate, whereas incorporation into alanine and glutamine is not affected. The effect of a work load on the pattern of glucose metabolism is thus different from that of insulin. 5. Increasing the concentration of glucose in the perfusion fluid from 1 to 20mm leads to changes of the pattern of glucose metabolism different from that brought about by insulin. 14CO2 production steadily increases whereas [14C]lactate and glycogen production levels off at 10mm-glucose, at values well below those reached in the presence of insulin. 6. In Langendorff hearts of animals rendered insulin-deficient by anti-insulin serum or streptozotocin, glucose uptake, formation of 14CO2 and [14C]lactate, and 14C incorporation into glycogen and oligosaccharides are decreased. In insulin-deficient working hearts, however, glucose uptake and 14CO2 production are normal, whereas incorporation of 14C into glycogen and [14C]lactate production are greatly decreased. 7. Insulin added to the perfusion fluid restores 14C incorporation from glucose into 14CO2, glycogen and lactate in the Langendorff heart from animals rendered insulin-deficient by anti-insulin serum; in hearts from streptozotocin-diabetic animals addition of insulin restores 14C incorporation into glycogen and lactate, but 14CO2 production remains about 50% below normal. 8. The bearing of these results on the problem of the mode of action of insulin is discussed.

Tricarboxylic acid cycle activity in perfused rat lungs after O2 exposure

1992 ◽  
Vol 262 (4) ◽  
pp. L495-L501 ◽  
Author(s):  
D. J. Bassett ◽  
S. S. Reichenbaugh
Keyword(s):  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Enzyme Inactivation ◽  
Pyridine Nucleotides ◽  
Acid Cycle ◽  
Metabolic Conditions ◽  
Steady State Levels ◽  
14Co2 Production ◽  
Tricarboxylic Acid Cycle Intermediates

O2-induced impairment of mitochondrial energy generation was examined in intact lungs isolated from rats after 18-30 h exposure to either air or 100% O2 in vivo. Mitochondrial metabolic rates were determined by separate measurements of 14CO2 production from [1-14C]pyruvate and [U-14C]palmitate, perfused under normal and stimulated metabolic conditions brought about by perfusion with the uncoupler of oxidative phosphorylation, 2,4-dinitrophenol (DNP). In the absence of DNP, O2 exposure did not significantly alter 14CO2 productions from either substrate. DNP increased lung pyruvate and palmitate catabolism to CO2 twofold in air-exposed lungs but did not alter 14CO2 production in lungs isolated from O2-exposed rats. These data demonstrated an O2-induced impairment of maximal mitochondrial metabolism of both pyruvate and palmitate that could not be explained by alterations in tissue free coenzyme A or by loss of pyridine nucleotides. However, comparisons of the steady-state levels of tricarboxylic acid cycle intermediates between O2- and air-exposed lungs did identify isocitrate dehydrogenase as a possible site of O2-induced enzyme inactivation.

C14-labeled glucose metabolism by bone from normal and parathyroid-treated rats

1965 ◽  
Vol 208 (5) ◽  
pp. 1036-1041 ◽  
Author(s):  
Haripada Chattopadhyay ◽  
Smith Freeman
Keyword(s):  
Glucose Metabolism ◽  
Tricarboxylic Acid Cycle ◽  
Bone Matrix ◽  
Tricarboxylic Acid ◽  
Bicarbonate Buffer ◽  
Acid Cycle ◽  
Growing Rats ◽  
Parathyroid Extract ◽  
Tricarboxylic Acid Cycle Intermediates

Calvaria and the metaphyseal and epiphyseal sections of tibia and femora freed of bone marrow from young growing rats were incubated in vitro for 2 hr at 37 C in Krebs-Ringer bicarbonate buffer containing 2 mm glucose. The glucose was labeled either in the 1 position or in the 6 position or uniformly in all positions with C14. The incorporation of C14 into citrate, lactate, and various tricarboxylic acid cycle intermediates was studied. The release of C14O2 and the incorporation of C14 into bone matrix were also measured. Results obtained from bones of untreated control, parathyroid extract-treated, and parathyroidectomized animals were compared. It was found that treatment of animals with parathyroid extract increased the total accumulation of labeled citrate and malate as well as the incorporation of these acids into bone mineral. Bones from extract-treated animals also exhibited a significant decrease in the total accumulation of radioactive fumarate, succinate, and pyruvate. Lactate was the major end product of glucose metabolism, but its accumulation was only slightly influenced by parathyroid extract.

Tricarboxylic acid cycle intermediates in human muscle during prolonged exercise

1990 ◽  
Vol 259 (5) ◽  
pp. C834-C841 ◽  
Author(s):  
K. Sahlin ◽  
A. Katz ◽  
S. Broberg
Keyword(s):  
Prolonged Exercise ◽  
Tricarboxylic Acid Cycle ◽  
Work Load ◽  
Tricarboxylic Acid ◽  
Glycogen Depletion ◽  
Energy Deficiency ◽  
Acid Cycle ◽  
Carbohydrate Depletion ◽  
Exercise Muscle ◽  
Tricarboxylic Acid Cycle Intermediates

Seven subjects cycled to fatigue [75 +/- 5 (SE) min] at a work load corresponding to approximately 75% of their maximal oxygen uptake. Biopsies were taken from the quadriceps femoris muscle at rest and during exercise. Muscle glycogen decreased from a preexercise level of 445 +/- 33 mmol glucosyl units/kg dry wt to 50 +/- 14 at fatigue. The sum of the measured tricarboxylic acid cycle intermediates (TCAI = malate + citrate + fumarate + oxaloacetate) was 0.49 +/- 0.05 mmol/kg dry wt at rest, increased to 4.41 +/- 0.23 after 5 min of exercise, and then decreased continuously to 3.33 +/- 0.29 and to 2.83 +/- 0.27 mmol/kg dry wt after 40 min of exercise and at fatigue (P less than 0.05 vs. 5 min), respectively. The point of fatigue was characterized by an enhanced deamination of AMP (judged by increase in IMP) and reduced contents (vs. 5 min of exercise) of lactate, pyruvate, and alanine. In contrast, acetylcarnitine (reflects the availability of acetylunits) increased threefold at the onset of exercise and was maintained approximately at this level until fatigue. It is concluded that prolonged exercise to fatigue at moderate work loads results in glycogen depletion, energy deficiency (increased AMP deamination), reduced levels of three-carbon compounds and TCAI (compared with the initial phase of exercise) but in maintained levels of acetylunits. The present data indicate that carbohydrate depletion may impair aerobic energy production by reducing the level of TCAI.

Effect of low glycogen on carbohydrate and energy metabolism in human muscle during exercise

1992 ◽  
Vol 262 (4) ◽  
pp. C975-C979 ◽  
Author(s):  
M. K. Spencer ◽  
Z. Yan ◽  
A. Katz
Keyword(s):  
Muscle Glycogen ◽  
Glycogen Content ◽  
Tricarboxylic Acid Cycle ◽  
Work Load ◽  
Tricarboxylic Acid ◽  
Human Muscle ◽  
Acid Cycle ◽  
Before And After ◽  
Tricarboxylic Acid Cycle Intermediates ◽  
Femoris Muscle

The effect of preexercise muscle glycogen content on the metabolic responses to exercise has been investigated. Seven men cycled at a work load calculated to elicit 75% of maximal oxygen uptake [211 +/- 17 (SE) W] on two occasions: 1) to fatigue (37.2 +/- 5.3 min) and 2) at the same work load and for the same duration as the first. Biopsies were obtained from the quadriceps femoris muscle before and after exercise. Before the first experiment, muscle glycogen was lowered by exercise and diet, and before the second experiment, muscle glycogen was elevated. In the low-glycogen condition (LG), muscle glycogen decreased from 182 +/- 15 at rest to 7 +/- 4 mmol glucosyl units/kg dry wt at fatigue, while in the high-glycogen condition (HG), glycogen decreased from 725 +/- 31 at rest to 353 +/- 53 mmol glucosyl units/kg dry wt at the end of exercise. Hexose monophosphates were not increased after LG exercise but increased approximately fivefold after HG exercise. Lactate increased more during HG exercise (LG = 16 +/- 5, HG = 61 +/- 7 mmol/kg dry wt; P less than or equal to 0.001), whereas IMP increased more during LG (LG = 2.8 +/- 0.6, HG = 0.9 +/- 0.2 mmol/kg dry wt; P less than or equal to 0.05). The increases in the sum of tricarboxylic acid cycle intermediates (TCAI; citrate+malate+fumarate) and acetylcarnitine (which is in equilibrium with acetyl CoA) were significantly greater during HG exercise (P less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Glycolytic origin of alanine formed in rat diaphragm muscle in vitro

1985 ◽  
Vol 231 (3) ◽  
pp. 801-804 ◽  
Author(s):  
M A Caldecourt ◽  
D J Cox ◽  
M C Sugden ◽  
T N Palmer
Keyword(s):  
Amino Acids ◽  
De Novo ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Diaphragm Muscle ◽  
Rat Diaphragm ◽  
Acid Cycle ◽  
Tricarboxylic Acid Cycle Intermediates ◽  
Alanine Production

In quarter-diaphragms from 40 h-starved rats the rate of glycogen mobilization is sufficient to account for the rate of lactate+pyruvate+alanine production. It is concluded, therefore, that alanine derives its carbon skeleton predominantly via glycolysis and not via synthesis de novo from tricarboxylic acid-cycle intermediates and related amino acids.

CO2 fixation and metabolic control in Pseudomonas saccharophila

1973 ◽  
Vol 19 (10) ◽  
pp. 1243-1250
Author(s):  
A. L. Donawa ◽  
M. Ishaque ◽  
M. I. H. Aleem
Keyword(s):  
Nadh Oxidase ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Acid Cycle ◽  
Tricarboxylic Acid Cycle Intermediates ◽  
Phosphorylated Sugars ◽  
Increased Activity ◽  
Ribulose Diphosphate Carboxylase ◽  
Glyoxylate Pathway ◽  
Pseudomonas Saccharophila

Hydrogen-dependent CO2-fixation experiments indicated the formation of several products including alanine, aspartate, phosphoglycerate, glutamate, and phosphorylated sugars by Pseudomonas saccharophila. The enzymes that are involved in the fixation are carboxydismutase, phosphoenolpyruvate carboxylase, and the malic enzyme. Ribulose diphosphate carboxylase, ribulose 5-phosphokinase, and ribose 5-phosphoisomerase show decreased activity whereas most of the tricarboxylic acid cycle enzymes and NADH oxidase show increased activity in heterotrophically grown cells. The glyoxylate pathway and permeases specific for the tricarboxylic acid cycle intermediates also vary in levels of activity according to the mode of growth. Although the oxygen tension appears to have an effect on enzyme levels during growth, the carbon source seems to be more important.

scholarly journals Triheptanoin partially restores levels of tricarboxylic acid cycle intermediates in the mouse pilocarpine model of epilepsy

2013 ◽  
Vol 129 (1) ◽  
pp. 107-119 ◽  
Author(s):  
Mussie G. Hadera ◽  
Olav B. Smeland ◽  
Tanya S. McDonald ◽  
Kah Ni Tan ◽  
Ursula Sonnewald ◽  
...  
Keyword(s):  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Acid Cycle ◽  
Pilocarpine Model ◽  
Tricarboxylic Acid Cycle Intermediates

scholarly journals Metabolic phases during the development of granulation tissue

1967 ◽  
Vol 105 (1) ◽  
pp. 333-341 ◽  
Author(s):  
Kirsti Lampiaho ◽  
E. Kulonen
Keyword(s):  
Granulation Tissue ◽  
Collagen Synthesis ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Pentose Phosphate ◽  
Acid Cycle ◽  
Short Period ◽  
Tricarboxylic Acid Cycle Intermediates ◽  
Observation Period

1. The metabolism of incubated slices of sponge-induced granulation tissue, harvested 4–90 days after the implantation, was studied with special reference to the capacity of collagen synthesis and to the energy metabolism. Data are also given on the nucleic acid contents during the observation period. Three metabolic phases were evident. 2. The viability of the slices for the synthesis of collagen was studied in various conditions. Freezing and homogenization destroyed the capacity of the tissue to incorporate proline into collagen. 3. Consumption of oxygen reached the maximum at 30–40 days. There was evidence that the pentose phosphate cycle was important, especially during the phases of the proliferation and the involution. The formation of lactic acid was maximal at about 20 days. 4. The capacity to incorporate proline into collagen hydroxyproline in vitro was limited to a relatively short period at 10–30 days. 5. The synthesis of collagen was dependent on the supply of oxygen and glucose, which latter could be replaced in the incubation medium by other monosaccharides but not by the metabolites of glucose or tricarboxylic acid-cycle intermediates.

The Ethylmalonyl-CoA Pathway for Methane-based Biorefineries: A Case Study of Using Methylosinus trichosporium OB3b, an Alpha-proteobacterial Methanotroph, for Producing 2-Hydroxyisobutyric Acid and 1,3-Butanediol from Methane

2021 ◽  
Author(s):  
Dung Hoang Anh Mai ◽  
Thu Thi Nguyen ◽  
Eun Yeol Lee
Keyword(s):  
Carbon Metabolism ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Methylosinus Trichosporium Ob3b ◽  
Methylosinus Trichosporium ◽  
Acid Cycle ◽  
Hydroxyisobutyric Acid ◽  
Tricarboxylic Acid Cycle Intermediates ◽  
Alpha Proteobacteria

The ethylmalonyl-CoA pathway is one of three known anaplerotic pathways that replenish tricarboxylic acid cycle intermediates and plays a major role in the carbon metabolism of many alpha-proteobacteria including Methylosinus...

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