scholarly journals Mechanism of hypoglycaemic action of methylenecyclopropylglycine

1989 ◽  
Vol 259 (3) ◽  
pp. 921-924 ◽  
Author(s):  
K Melde ◽  
H Buettner ◽  
W Boschert ◽  
H P O Wolf ◽  
S Ghisla
Keyword(s):  
Plasma Concentrations ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Toxic Metabolite ◽  
Beta Oxidation ◽  
Pyruvate Metabolism ◽  
Oral Ingestion ◽  
Chain Acyl ◽  
Branched Chain ◽  
Coa Thioesters

The effects of methylenecyclopropylglycine (MCPG), the lower homologue of hypoglycin A, on starved rats are described. Upon oral ingestion of MCPG (43 mg/kg), a 50% decrease in blood glucose compared with controls was observed after 4 h. The plasma concentrations of lactate and non-esterified fatty acids were substantially increased during this period. The activity of general acyl-CoA dehydrogenase from isolated rat liver mitochondria was not significantly changed. By contrast, the activity of 2-methyl-(branched-chain)-acyl-CoA dehydrogenase decreased by over 80%. The enzyme activity of enoyl-CoA hydratase (crotonase) from pig kidneys decreased by 80% on incubation with the hypothetically toxic metabolite of MCPG, methylenecyclopropylformyl-CoA. These results suggest that the inhibition spectrum of MCPG is quite different from that of hypoglycin A and that similar physiological effects might result from inhibition of different enzymes of beta-oxidation, e.g. hypoglycaemia and lacticacidemia. Accumulation of medium-chain acyl-CoA thioesters is probably at the origin of disturbances in pyruvate metabolism.

scholarly journals Metabolic consequences of methylenecyclopropylglycine poisoning in rats

1991 ◽  
Vol 274 (2) ◽  
pp. 395-400 ◽  
Author(s):  
K Melde ◽  
S Jackson ◽  
K Bartlett ◽  
H S A Sherratt ◽  
S Ghisla
Keyword(s):  
Amino Acids ◽  
Ketone Bodies ◽  
Blood Glucose Concentration ◽  
Plasma Concentrations ◽  
Liver Mitochondria ◽  
Branched Chain Amino Acids ◽  
Oxidation Products ◽  
Rat Liver Mitochondria ◽  
Toxic Metabolite ◽  
Branched Chain

We describe the effects of methylenecyclopropylglycine in fasted rats. A 75% decrease in the blood glucose concentration and an increase of lactate and pyruvate were observed 6 h after administration of 100 mg of this amino acid/kg. By contrast with the effects reported for hypoglycin [Williamson & Wilson (1965) Biochem. J. 94, 19c-21c], the plasma concentrations of ketone bodies decreased after administration of methylenecyclopropylglycine and the concentrations of branched-chain amino acids in the plasma were increased 6-fold. The oxidation of decanoylcarnitine or of palmitate was nearly completely inhibited in rat liver mitochondria from methylenecyclopropylglycine-poisoned rats. The activities of acetoacetyl-CoA and of 3-oxoacyl-CoA thiolase were decreased to 25% and less than 10% of the controls. There was a pronounced aciduria, due to the excretion of dicarboxylic acids and of oxidation products of branched-chain amino acids. The accumulation of the toxic metabolite methylenecyclopropylformyl-CoA in the mitochondrial matrix was detected after administration of methylenecyclopropylglycine. Similarly we confirmed experimentally that methylenecyclopropylacetyl-CoA accumulates in mitochondria incubated with methylenecyclopropylpyruvate.

scholarly journals Effects of riboflavin deficiency and clofibrate treatment on the five acyl-CoA dehydrogenases in rat liver mitochondria

1988 ◽  
Vol 254 (2) ◽  
pp. 477-481 ◽  
Author(s):  
K Veitch ◽  
J P Draye ◽  
F Van Hoof ◽  
H S A Sherratt
Keyword(s):  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Straight Chain ◽  
Riboflavin Deficiency ◽  
Deficient Diet ◽  
Mitochondrial Fractions ◽  
Chain Acyl ◽  
Branched Chain ◽  
Acyl Coa Dehydrogenases ◽  
Riboflavin Deficient

Rats were maintained on a riboflavin-deficient diet or on a diet containing clofibrate (0.5%, w/w). The activities of the mitochondrial FAD-dependent straight-chain acyl-CoA dehydrogenases (butyryl-CoA, octanoyl-CoA and palmitoyl-CoA) and the branched-chain acyl-CoA dehydrogenases (isovaleryl-CoA and isobutyryl-CoA) involved in the degradation of branched-chain acyl-CoA esters derived from branched-chain amino acids were assayed in liver mitochondrial extracts prepared in the absence and presence of exogenous FAD. These activities were low in livers from riboflavin-deficient rats (11, 28, 16, 6 and less than 2% of controls respectively) when prepared in the absence of exogenous FAD, and were not restored to control values when prepared in 25 microM-FAD (29, 47, 28, 7 and 17%). Clofibrate feeding increased the activities of butyryl-CoA, octanoyl-CoA and palmitoyl-CoA dehydrogenases (by 48, 116 and 98% of controls respectively), but not, by contrast, the activities of isovaleryl-CoA and isobutyryl-CoA dehydrogenases (62 and 102% of controls respectively). The mitochondrial fractions from riboflavin-deficient and from clofibrate-fed rats oxidized palmitoylcarnitine in State 3 at rates of 32 and 163% respectively of those from control rats.

scholarly journals Steady-state concentrations of coenzyme A, acetyl-coenzyme A and long-chain fatty acyl-coenzyme A in rat-liver mitochondria oxidizing palmitate

1965 ◽  
Vol 97 (2) ◽  
pp. 587-594 ◽  
Author(s):  
PB Garland ◽  
D Shepherd ◽  
DW Yates
Keyword(s):  
Rat Liver ◽  
Coenzyme A ◽  
Liver Mitochondria ◽  
Fatty Acyl ◽  
Rat Liver Mitochondria ◽  
Beta Oxidation ◽  
Acetyl Coa ◽  
Acetyl Coenzyme A ◽  
Acyl Coenzyme A ◽  
Long Chain

1. Fluorimetric assays are described for CoASH, acetyl-CoA and long-chain fatty acyl-CoA, and are sensitive to at least 50mumumoles of each. 2. Application of these assays to rat-liver mitochondria oxidizing palmitate in the absence and presence of carnitine indicated two pools of intramitochondrial CoA. One pool could be acylated by palmitate and ATP, and the other pool acylated by palmitate with ATP and carnitine, or by palmitoylcarnitine alone. 3. The intramitochondrial content of acetyl-CoA is increased by the oxidation of palmitate both in the absence and presence of l-malate. 4. The conversion of palmitoyl-CoA into acetyl-CoA by beta-oxidation takes place without detectable accumulation of acyl-CoA intermediates.

Sign in / Sign up

Export Citation Format

Share Document