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.

scholarly journals The activities of the citric acid-cycle enzymes in rat bone-marrow cells

1968 ◽  
Vol 108 (3) ◽  
pp. 413-415
Author(s):  
Eugene Goldwasser
Keyword(s):  
Bone Marrow ◽  
Citric Acid ◽  
Citric Acid Cycle ◽  
Citrate Synthase ◽  
Bone Marrow Cells ◽  
Mitochondrial Enzymes ◽  
Acid Cycle ◽  
Citric Acid Cycle Enzymes ◽  
Rat Bone ◽  
Marrow Cells

The activities of the eight citric acid-cycle enzymes of rat bone-marrow cells were determined along with several other mitochondrial and non-mitochondrial enzymes. Four of the citric acid-cycle enzymes (aconitase, succinyl-CoA thiokinase, α-oxoglutarate dehydrogenase and succinate dehydrogenase) have closely similar low activities; two [isocitrate dehydrogenase (NAD) and citrate synthase] have intermediate activities; the remaining two (malate dehydrogenase and fumarase) have high activities. The other enzymes surveyed also exhibited a spread of three orders of magnitude, the mitochondrial enzymes showing no less variation than the others.

The extraordinary mitochondrion and unusual citric acid cycle in Trypanosoma brucei

2005 ◽  
Vol 33 (5) ◽  
pp. 967 ◽  
Author(s):  
F.R. Opperdoes ◽  
J.J. van Hellemond ◽  
A.G.M. Tielens
Keyword(s):  
Citric Acid ◽  
Trypanosoma Brucei ◽  
Citric Acid Cycle ◽  
Acid Cycle

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.

Organization of citric acid cycle enzymes into a multienzyme cluster

FEBS Letters ◽  
1986 ◽  
Vol 201 (2) ◽  
pp. 267-270 ◽  
Author(s):  
Sarah J. Barnes ◽  
P.D.J. Weitzman
Keyword(s):  
Citric Acid ◽  
Citric Acid Cycle ◽  
Acid Cycle ◽  
Citric Acid Cycle Enzymes

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.

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