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 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.

Effect of carnitine on branched-chain amino acid oxidation by liver and skeletal muscle.

1978 ◽  
Vol 234 (5) ◽  
pp. E494 ◽  
Author(s):  
H S Paul ◽  
S A Adibi
Keyword(s):  
Amino Acids ◽  
Liver Mitochondria ◽  
Branched Chain Amino Acids ◽  
Diabetic Rats ◽  
Acid Oxidation ◽  
Acyltransferase Activity ◽  
Remarkable Effect ◽  
Carnitine Acyltransferase ◽  
Branched Chain Amino Acid ◽  
Branched Chain

The effect of L-carnitine (0.5-2.0 mM) on the rates of alpha-decarboxylation of 1-14C-labeled branched-chain amino acids by gastrocnemius muscle and liver homogenates of fed rats was investigated. Carnitine increased the rate of alpha-decarboxylation of leucine (125%) and valine (28%) by muscle, but it was without effect on the oxidation of these amino acids by liver. Carnitine increased the rate of alpha-decarboxylation of alpha-ketoisocaproate by both tissues. This effect was more pronounced in muscle (130% increase) than in liver (41% increase). The activity of carnitine acyltransferase, with isovaleryl-CoA as a substrate, was 18 times higher in muscle mitochondria than in liver mitochondria. Both starvation and diabetes increased the rate of alpha-decarboxylation of leucine by muscle without having a remarkable effect on the concentration of carnitine or the activity of carnitine acyltransferase. We conclude that: a) carnitine stimulates decarboxylation of branched-chain amino acids by increasing the conversion of their ketoanalogues into carnitine esters, b) a greater carnitine acyltransferase activity in muscle than in liver may be responsible for the greater carnitine effect in muscle, c) carnitine does not appear responsible for the enhancement of leucine oxidation by muscle of starved and diabetic rats.

scholarly journals Association between plasma concentrations of branched-chain amino acids and adipokines in Japanese adults without diabetes

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Ryoko Katagiri ◽  
Atsushi Goto ◽  
Sanjeev Budhathoki ◽  
Taiki Yamaji ◽  
Hiroshi Yamamoto ◽  
...  
Keyword(s):  
Amino Acids ◽  
Plasma Concentrations ◽  
Branched Chain Amino Acids ◽  
Japanese Adults ◽  
Branched Chain

Amino acid metabolism in the Zucker diabetic fatty rat: effects of insulin resistance and of type 2 diabetes

2004 ◽  
Vol 82 (7) ◽  
pp. 506-514 ◽  
Author(s):  
Enoka P Wijekoon ◽  
Craig Skinner ◽  
Margaret E Brosnan ◽  
John T Brosnan
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Plasma Concentrations ◽  
Branched Chain Amino Acids ◽  
Insulin Resistant ◽  
Branched Chain

We investigated amino acid metabolism in the Zucker diabetic fatty (ZDF Gmi fa/fa) rat during the prediabetic insulin-resistant stage and the frank type 2 diabetic stage. Amino acids were measured in plasma, liver, and skeletal muscle, and the ratios of plasma/liver and plasma/skeletal muscle were calculated. At the insulin-resistant stage, the plasma concentrations of the gluconeogenic amino acids aspartate, serine, glutamine, glycine, and histidine were decreased in the ZDF Gmi fa/fa rats, whereas taurine, α-aminoadipic acid, methionine, phenylalanine, tryptophan, and the 3 branched-chain amino acids were significantly increased. At the diabetic stage, a larger number of gluconeogenic amino acids had decreased plasma concentrations. The 3 branched-chain amino acids had elevated plasma concentrations. In the liver and the skeletal muscles, concentrations of many of the gluconeogenic amino acids were lower at both stages, whereas the levels of 1 or all of the branched-chain amino acids were elevated. These changes in amino acid concentrations are similar to changes seen in type 1 diabetes. It is evident that insulin resistance alone is capable of bringing about many of the changes in amino acid metabolism observed in type 2 diabetes.Key words: plasma amino acids, liver amino acids, muscle amino acids, gluconeogenesis.

scholarly journals Dietary Intakes and Circulating Concentrations of Branched-Chain Amino Acids in Relation to Incident Type 2 Diabetes Risk Among High-Risk Women with a History of Gestational Diabetes Mellitus

2018 ◽  
Vol 64 (8) ◽  
pp. 1203-1210 ◽  
Author(s):  
Deirdre K Tobias ◽  
Clary Clish ◽  
Samia Mora ◽  
Jun Li ◽  
Liming Liang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Amino Acids ◽  
Gestational Diabetes ◽  
Plasma Concentrations ◽  
Branched Chain Amino Acids ◽  
High Risk Women ◽  
History Of ◽  
Branched Chain

Abstract BACKGROUND Circulating branched-chain amino acids (BCAAs; isoleucine, leucine, valine) are consistently associated with increased type 2 diabetes (T2D) risk, but the relationship with dietary intake of BCAAs is less clear. METHODS The longitudinal Nurses' Health Study II cohort conducted a blood collection from 1996 to 1999. We profiled plasma metabolites among 172 incident T2D cases and 175 age-matched controls from women reporting a history of gestational diabetes before blood draw. We estimated dietary energy-adjusted BCAAs from food frequency questionnaires. We used conditional logistic regression models to estimate odds ratios (OR) and 95% CI of T2D risk across quartiles (Q1–Q4) of BCAAs, adjusting for age, body mass index (BMI), physical activity, family history, and other established risk factors. We also assessed joint exposure to below/above medians of diet and plasma concentrations, with lower diet/lower plasma as reference. RESULTS Dietary and plasma BCAA concentrations were positively associated with incident T2D (diet Q4 vs Q1 OR = 4.6, CI = 1.6, 13.4; plasma Q4 vs Q1 OR = 4.4, CI = 1.4, 13.4). Modeling the joint association indicated that higher diet BCAAs were associated with T2D when plasma concentrations were also higher (OR = 6.0, CI = 2.1, 17.2) but not when concentrations were lower (OR = 1.6, CI = 0.61, 4.1). Conversely, higher plasma BCAAs were associated with increased T2D for either lower or higher diet. CONCLUSIONS Independent of BMI and other risk factors, higher diet and plasma BCAA concentrations were associated with an increased incident T2D risk among high-risk women with a history of gestational diabetes, supporting impaired BCAA metabolism as conferring T2D risk.

scholarly journals Effects on nitrogen balance and metabolism of branched-chain amino acids by growing pigs of supplementing isoleucine and valine to diets with adequate or excess concentrations of dietary leucine

2020 ◽  
Vol 98 (11) ◽  
Author(s):  
Woong B Kwon ◽  
Jose A Soto ◽  
Hans H Stein
Keyword(s):  
Amino Acids ◽  
Plasma Concentration ◽  
Plasma Concentrations ◽  
Basal Diet ◽  
Branched Chain Amino Acids ◽  
Growing Pigs ◽  
Plasma Urea ◽  
N Retention ◽  
Branched Chain ◽  
Dietary Treatments

Abstract Diets based on high levels of corn protein have elevated concentrations of Leu, which may negatively affect N retention in pigs. An experiment was, therefore, conducted to test the hypothesis that Ile and Val supplementation may overcome the detrimental effects of excess dietary Leu on N balance and metabolism of branched-chain amino acids (BCAA) in growing pigs. A total of 144 barrows (initial body weight: 28.5 kg) were housed in metabolism crates and randomly assigned to 1 of 18 dietary treatments. The basal diet contained 0.98% standardized ileal digestible (SID) Lys and had SID Leu, Val, and Ile ratios to SID Lys of 100%, 60%, and 43%, respectively. Crystalline l-Leu (0% or 2.0%), l-Ile (0%, 0.1%, or 0.2%), and l-Val (0%, 0.1%, or 0.2%) were added to the basal diet resulting in a total of 18 dietary treatments that were arranged in a 2 × 3 × 3 factorial. Urine and fecal samples were collected for 5 d after 7 d of adaptation. Blood, skeletal muscle, and liver samples were collected at the conclusion of the experiment. There were no three-way interactions among the main effects. Excess Leu in diets reduced (P < 0.05) N retention and biological value of protein and increased (P < 0.001) plasma urea N (PUN), but PUN was reduced (P < 0.05) as dietary Val increased. Concentrations of Leu in the liver were greater (P < 0.001) in pigs fed excess Leu diets than in pigs fed adequate Leu diets, but concentrations of BCAA in muscle were greater (P < 0.05) in pigs fed low-Leu diets. Increasing dietary Ile increased (P < 0.001) plasma-free Ile and plasma concentration of the Ile metabolite, α-keto-β-methylvalerate, but the increase was greater in diets without excess Leu than in diets with excess Leu (interaction, P < 0.001). Plasma concentrations of Val and the Val metabolite α-keto isovalerate increased (P < 0.001) with increasing dietary Val in diets with adequate Leu, but not in diets with excess Leu (interaction, P < 0.001). Increasing dietary Leu increased (P < 0.001) plasma-free Leu and plasma concentration of the Leu metabolite, α-keto isocaproate (KIC). In contrast, increased dietary Val reduced (P < 0.05) the plasma concentration of KIC. In conclusion, excess dietary Leu reduced N retention and increased PUN in growing pigs, but Val supplementation to excess Leu diets may increase the efficiency of amino acid utilization for protein synthesis as indicated by reduced PUN.

scholarly journals Effects of ketone bodies on amino acid metabolism in isolated rat diaphragm

1976 ◽  
Vol 154 (3) ◽  
pp. 709-716 ◽  
Author(s):  
G Palaiologos ◽  
P Felig
Keyword(s):  
Amino Acids ◽  
Free Amino Acids ◽  
Free Amino ◽  
Acid Metabolism ◽  
Ketone Bodies ◽  
Branched Chain Amino Acids ◽  
Tissue Content ◽  
Constant Rate ◽  
Branched Chain ◽  
Glutamine Production

1. Diaphragms from 48h-starved rats were incubated in Krebs-Ringer bicarbonate medium at 37degreesC for 30min and then transferred into new medium and incubated for 1, 2 and 3 h. 2. The amount of free amino acids found at the end of each time of incubation was larger than the amount at the beginning of incubation, indicating that in this system proteolysis is prevailing. 3. The diaphragms was releasing mainly alanine and glutamine into the incubation medium. 4. Within the periods of incubation the release and metabolism of free amino acids was proceeding at a constant rate. 5. Addition of sodium DL-3-hydroxybutyrate decreased the tissue content of several amino acids, among which were tyrosine and phenylalanine, suggesting that proteolysis was decreased by ketone bodies. 6. In the presence of glucose (10mM) and branched-chain amino acids (0.5mM), sodium DL-3-hydroxybutyrate at concentrations of 4 or 6 mM resulted in 30% decrease in tissue alanine content and a 20% decline in alanine release. Release of taurine and glutamine was decreased by 19 and 16% respectively with 6 mM-sodium DL-3-hydroxybutyrate. Addition of sodium acetoacetate (1-3mM) also resulted in a 20-35% decrease in tissue content of alanine, glutamine and taurine and in a 15-24% decrease of alanine and glutamine release. Smaller decreases (less than 15%) in the release of glycine, threonine, proline, serine and aspartate were also observed in the presence of sodium DL-3-hydroxybutyrate or sodium acetoacetate. 7. Substitution of pyruvate (1.0mM) for glucose in the presence of acetoacetate restored alanine and glutamine production to control values. In the presence of acetoacetate, pyruvate also increased the tissue content of aspartate by 77% and decreased the tissue content of glutamate by 30%. 8. It is suggested that in diaphragms from starved rats, ketone bodies (a) in the absence of other substrates inhibit protein catabolism and (b) in the presence of glucose and branched-chain amino acids decrease alanine and glutamine production, by inhibiting glycolysis.

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