Lactate Reverses Insulin-Induced Hypoglycemic Stupor in Suckling—Weanling Mice: Biochemical Correlates in Blood, Liver, and Brain

1983 ◽  
Vol 3 (4) ◽  
pp. 498-506 ◽  
Author(s):  
Jean Holowach Thurston ◽  
Richard E. Hauhart ◽  
James A. Schiro
Keyword(s):  
Amino Acids ◽  
Citric Acid ◽  
Energy Metabolism ◽  
Citric Acid Cycle ◽  
Plasma Lactate ◽  
Brain Glucose ◽  
Acid Cycle ◽  
Glucose Levels ◽  
Glycolytic Intermediates ◽  
Lactate Levels

The recovery of weanling mice from insulin-induced hypoglycemic stupor–coma after injection of sodium -l(+)-lactate (18 mmol/kg) was as rapid (10 min) as in litter-mates treated with glucose (9 mmol/kg). Stimulated by this dramatic action, we studied the effects of lactate injection on brain carbohydrate and energy metabolism in normal and hypoglycemic mice; blood and liver tissue were also studied. Ten minutes after lactate injection in normal mice, plasma lactate levels increased by 15 mmol/L; plasma glucose levels were unchanged, but the β-hydroxybutyrate concentration fell 59%. In the brains of these animals, glucose levels increased 2.3-fold, and there were significant increases in brain glycogen (10%), glucose-6-phosphate (27%), lactate (68%), pyruvate (37%), citrate (12%), and malate (19%); the increase in α-ketoglutarate (32%) was not significant. Lactate injection reduced the cerebral glucose-use rate 40%. These changes were not due to lactate-induced increases in blood [HCO−3] and pH (examined by injection of 15 mmol/kg sodium bicarbonate). Although lactate injection of hypoglycemic mice doubled levels of glucose in plasma and brain (not significant) and most of the cerebral glycolytic intermediates, values were far below normal (still in the range seen in hypoglycemic animals). By contrast, citrate and α-ketoglutarate levels returned to normal; the large increase in malate was not significant. Reduced glutamate levels increased to normal, and elevated aspartate levels fell below normal. Thus, recovery from hypoglycemic stupor does not necessarily depend on normal levels of plasma and/or brain glucose (or glycolytic intermediates). Near normal levels of the Krebs citric acid cycle intermediates suggest that changes in these metabolites, amino acids, or derived substrates relate to the dramatic recovery of hypoglycemic mice after lactate injection.

ENERGY METABOLISM OF PHYCOMYCES BLAKESLEEANUS THE CITRIC ACID CYCLE AND ASSOCIATED AMINO ACIDS

1966 ◽  
Vol 12 (1) ◽  
pp. 1-4 ◽  
Author(s):  
Edwin C. Gangloff
Keyword(s):  
Amino Acids ◽  
Citric Acid ◽  
Energy Metabolism ◽  
Organic Acids ◽  
High Activity ◽  
Citric Acid Cycle ◽  
Specific Activity ◽  
Nitrogen Compounds ◽  
Phycomyces Blakesleeanus ◽  
Acid Cycle

All of the intermediates of the citric acid cycle are shown to be present in the mycelium of 6-day cultures of P. blakesleeanus grown on glucose and on ammonium sulfate, and fed non-radioactive acetate on the fourth and fifth days and acetate-1-C14 on the fifth day of incubation.The concentration of organic acids and certain amino acids, and their specific activity is reported. The high activity of the latter is thought to indicate the presence of a highly labeled pool of nitrogen compounds persisting from the early anabolic reactions after acetate-1-C14 administration.

Effect of cyclic AMP on catabolite-repressed zoosporangial formation in Phytophthora capsici

1977 ◽  
Vol 55 (7) ◽  
pp. 840-843 ◽  
Author(s):  
M. Yoshikawa ◽  
H. Masago
Keyword(s):  
Amino Acids ◽  
Citric Acid ◽  
Cyclic Amp ◽  
Catabolite Repression ◽  
Citric Acid Cycle ◽  
Phytophthora Capsici ◽  
Antimycin A ◽  
Acid Cycle

Zoosporangial formation in Phytophthora capsici was sensitively inhibited by glucose and other catabolites including sugars, citric acid cycle acids, and amino acids, but was only slightly inhibited by 3-O-methylglucose and 2-deoxyglucose and by other seemingly weak catabolites. The inhibitions were specifically prevented by cyclic AMP among the various related nucleotides evaluated. The reversing effect by cyclic AMP was observed only on zoosporangial formation that was partially repressed by catabolites, but the completely repressed zoosporangial formation could not be reversed by cyclic AMP. Furthermore, cyclic AMP failed in reversing zoosporangial formation that was inhibited by antibiotics such as antimycin A and cycloheximide. The results suggested that the initiation of zoosporangial formation in the fungus is under the control of catabolite repression that is mediated by cyclic AMP.

STUDIES ON WHEAT PLANTS USING C14 COMPOUNDS: IV. DISTRIBUTION OF C14 IN GLUTAMIC ACID, ASPARTIC ACID, AND THREONINE ARISING FROM ACETATE-1-C14 AND -2-C14

1957 ◽  
Vol 35 (6) ◽  
pp. 365-371 ◽  
Author(s):  
E. Bilinski ◽  
W. B. McConnell
Keyword(s):  
Amino Acids ◽  
Citric Acid ◽  
Glutamic Acid ◽  
Aspartic Acid ◽  
Citric Acid Cycle ◽  
Carbon Skeleton ◽  
Major Pathway ◽  
Acid Cycle ◽  
Carbon 14

Glutamic acid, aspartic acid, and threonine isolated from the gluten of wheat plants to which acetate-1-C14 or -2-C14 was administered during growth have been degraded to determine the complete intramolecular distribution of C14. Sixty-three per cent of the activity in glutamic acid arising from acetate-1-C14 was in carbon-5 and 20% in carbon-1; glutamic acid from acetate-2-C14 contained 43% of the activity in carbon-4 and about 18% in each of carbons 2 and 3. Acetate-1-C14 resulted in labelling largely in the terminal carbons of aspartic acid, and acetate-2-C14 preferentially labelled the internal carbons. The results show that the Krebs' citric acid cycle provides a major pathway for the biosynthesis of the dicarboxylic amino acids of wheat gluten.Striking parallelism in the intramolecular distribution of carbon-14 in aspartic acid and threonine demonstrates that these amino acids are closely linked biosynthetically and is in accord with the idea that aspartic acid provides the carbon skeleton for threonine.

scholarly journals Type-2-diabetes Alters CSF but not Plasma Metabolomic and AD Risk Profiles in Vervet Monkeys

2019 ◽  
Author(s):  
Kylie Kavanagh ◽  
Stephen M. Day ◽  
Morgan C. Pait ◽  
William R. Mortiz ◽  
Christopher B. Newgard ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Cerebral Metabolism ◽  
Vervet Monkeys ◽  
Plasma Lactate ◽  
Glucose Levels ◽  
Highly Correlated ◽  
Lactate Levels ◽  
The Brain

AbstractEpidemiological studies suggest that individuals with type 2 diabetes (T2D) have a 2-4 fold increased risk for developing Alzheimer’s disease (AD), however the exact mechanisms linking the two disease is unknown. In both conditions, the majority of pathophysiological changes (including glucose and insulin dysregulation, insulin resistance, and AD-related changes in Aβ and tau) occur decades before the onset of clinical symptoms and diagnosis. In this study, we investigated the relationship between metabolic biomarkers associated with T2D and AD-related pathology, including Aβ levels, from cerebrospinal fluid (CSF) and fasting plasma of healthy, prediabetic (PreD), and T2D vervet monkeys (Chlorocebus aethiops sabeus). Consistent with the human disease, T2D monkeys have increased plasma and CSF glucose levels as they transition from normoglycemia to pre-diabetic and diabetic states. Although plasma levels of acylcarnitines and amino acids remained largely unchanged, peripheral hyperglycemia correlated with decreased CSF acylcarnitines and CSF amino acids, including branched chain amino acid (BCAA) concentrations, suggesting profound changes in cerebral metabolism coincident with systemic glucose dysregulation. Moreover, CSF Aβ40 and CSF Aβ42 levels decreased in T2D monkeys, a phenomenon observed in the human course of AD which coincides with increased amyloid deposition within the brain. In agreement with our previous studies in mice, CSF Aβ40 and CSF Aβ42 were highly correlated with CSF glucose levels, suggesting that glucose levels in the brain are associated with changes in Aβ metabolism. Interestingly, CSF Aβ40 and CSF Aβ42 levels were also highly correlated with plasma but not CSF lactate levels, suggesting that plasma lactate might serve as a potential biomarker of disease progression in AD. Moreover, CSF glucose and plasma lactate levels were correlated with CSF amino acid and acylcarnitine levels, demonstrating alterations in cerebral metabolism occurring with the onset of T2D. Together, these data suggest that peripheral metabolic changes associated with the development of T2D produce alterations in brain metabolism that lead to early changes in the amyloid cascade, similar to those observed in pre-symptomatic AD.

The extraordinary mitochondrion and unusual citric acid cycle in Trypanosoma brucei

2005 ◽  
Vol 33 (5) ◽  
pp. 967-971 ◽  
Author(s):  
J.J. van Hellemond ◽  
F.R. Opperdoes ◽  
A.G.M. Tielens
Keyword(s):  
Citric Acid ◽  
Energy Metabolism ◽  
Trypanosoma Brucei ◽  
Citric Acid Cycle ◽  
Clinical Importance ◽  
African Trypanosomes ◽  
Acid Cycle ◽  
Fermentative Metabolism ◽  
Influence Of Substrate ◽  
Citric Acid Cycle Enzymes

African trypanosomes are parasitic protozoa that cause sleeping sickness and nagana. Trypanosomes are not only of scientific interest because of their clinical importance, but also because these protozoa contain several very unusual biological features, such as their specially adapted mitochondrion and the compartmentalization of glycolytic enzymes in glycosomes. The energy metabolism of Trypanosoma brucei differs significantly from that of their hosts and changes drastically during the life cycle. Despite the presence of all citric acid cycle enzymes in procyclic insect-stage T. brucei, citric acid cycle activity is not used for energy generation. Recent investigations on the influence of substrate availability on the type of energy metabolism showed that absence of glycolytic substrates did not induce a shift from a fermentative metabolism to complete oxidation of substrates. Apparently, insect-stage T. brucei use parts of the citric acid cycle for other purposes than for complete degradation of mitochondrial substrates. Parts of the cycle are suggested to be used for (i) transport of acetyl-CoA units from the mitochondrion to the cytosol for the biosynthesis of fatty acids, (ii) degradation of proline and glutamate to succinate, (iii) generation of malate, which can then be used for gluconeogenesis. Therefore the citric acid cycle in trypanosomes does not function as a cycle.

The effects of imidazole-4-acetic acid on cerebral carbohydrate metaboifsm

1982 ◽  
Vol 60 (12) ◽  
pp. 1610-1617
Author(s):  
M. Bovell ◽  
T. Chung ◽  
V. MacMillan ◽  
R. Shankaran
Keyword(s):  
Acetic Acid ◽  
Citric Acid ◽  
Cerebral Hemisphere ◽  
Citric Acid Cycle ◽  
High Energy ◽  
High Energy Phosphate ◽  
Acid Cycle ◽  
Glycolytic Intermediates ◽  
Tissue Contents ◽  
Eeg Pattern

The effects of intravenous administration of 50–400 mg/kg imidazole-4-acetic acid (IMA) on the carbohydrate metabolism of the rat brain were assessed by measurement of the cerebral hemisphere contents of energy phosphates and glycolytic – citric acid cycle metabolites. IMA (100–400 mg/kg) produced a spectrum of electroencephalographic (EEG) change ranging from desynchronization to electrical suppression which was associated with unchanged tissue contents of ATP, ADP, and AMP, increasing levels of phosphocreatine, glucose, and aspartate, and decreasing levels of pyruvate, lactate, α-ketoglutaratc, and malate. The changes in glycolytic intermediates were present within 5 min of injecting IMA (200 mg/kg) and the pattern suggested a suppression of glycolysis. The EEG stage of electrical suppression with episodic spiking (400 mg/kg) was associated with a 30% reduction of cortical high-energy phosphate use. The lowest dose of IMA (50 mg/kg) resulted in episodic EEG desynchronization which was associated with no significant changes of the measured metabolites. The results indicate that IMA is associated with metabolite changes that are compatible with a state of cerebral depression and that the desynchronous EEG pattern is without a biochemical con-elate of increased neuronal activity.

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