scholarly journals Metabolic effects of propionate in normal and vitamin B12-deficient rats

1971 ◽  
Vol 124 (3) ◽  
pp. 501-507 ◽  
Author(s):  
D. L. Williams ◽  
G. H. Spray ◽  
R. Hems ◽  
D. H. Williamson
Keyword(s):  
Vitamin B12 ◽  
Pyruvate Carboxylase ◽  
Ketone Bodies ◽  
Metabolic Effects ◽  
Acetyl Coa ◽  
Twofold Increase ◽  
Glucose Synthesis ◽  
Lactate And Pyruvate ◽  
Absolute Decrease ◽  
Deficient Group

1. Administration of propionate caused a twofold increase in the concentrations of lactate and pyruvate in the blood of vitamin B12-deficient rats, whereas there was a slight decrease in lactate and a 50% increase in pyruvate in normal rats. 2. Concentrations of total ketone bodies in the blood of normal rats were not significantly altered by propionate administration but the [3-hydroxybutyrate]/[acetoacetate] ratio decreased from 3.0 to 2.0. In the vitamin B12-deficient rats there was a 40% decrease in total ketone bodies and a change in the ratio from 3.4 to 1.2. 3. The changes in the concentration of ketone bodies in freeze-clamped liver preparations were similar in pattern to those observed in blood. 4. Propionate administration caused a decrease in the concentration of acetyl-CoA in the livers of both groups of animals, but the absolute decrease was greater in the vitamin B12-deficient group. The decrease in the concentration of CoA was similar in both groups. 5. As in blood, there were threefold increases in the concentrations of lactate and pyruvate in the livers of the vitamin B12-deficient rats after propionate administration, whereas there was no significant change in the concentrations of these metabolites in the normal rats. 6. There was a 50% inhibition of glucose synthesis in perfused livers from vitamin B12-deficient rats when lactate and propionate were substrates as compared with lactate alone. 7. It is concluded that the conversion of lactate into glucose is inhibited in vitamin B12-deficient rats after propionate administration, and that this effect is due to inhibition of the pyruvate carboxylase step resulting from a decrease in acetyl-CoA concentration and a postulated increase in methylmalonyl-CoA concentration.

scholarly journals Metabolic studies in experimental liver disease resulting from d(+)-galactosamine administration

1972 ◽  
Vol 130 (1) ◽  
pp. 37-44 ◽  
Author(s):  
Christopher O. Record ◽  
K. G. M. M. Alberti ◽  
Dermot H. Williamson
Keyword(s):  
Phosphoenolpyruvate Carboxylase ◽  
Ketone Bodies ◽  
Soluble Fraction ◽  
Mass Action ◽  
Significant Elevation ◽  
Control Value ◽  
Glucose Synthesis ◽  
Lactate And Pyruvate ◽  
Experimental Liver ◽  
Pyruvate Ratio

1. In confirmation of previous work, administration of d(+)-galactosamine (0.5–0.75g/kg body wt.) to rats caused a hepatitis with histological evidence of liver damage and a 9-fold rise in aspartate aminotransferase activity in serum. 2. There was a significant elevation of blood lactate and pyruvate concentrations in 24h-starved rats treated with galactosamine but no change in the [lactate]/[pyruvate] ratio. 3-Hydroxybutyrate and acetoacetate concentrations in blood were decreased. 3. The changes in the concentrations of lactate, pyruvate and ketone bodies in the freeze-clamped liver were parallel to those observed in the blood. 4. In the livers of 24h-starved galactosamine-treated rats there were large increases in the concentrations of alanine (3-fold), citrate (5-fold), 2-oxoglutarate (4-fold), with smaller increases in malate, glutamate and aspartate. There was a 4-fold rise in the value of the mass-action ratio of the alanine aminotransferase system in the livers of galactosamine-treated rats when compared to controls. 5. There was a significant decrease in the activities of aspartate and alanine aminotransferases in the cytoplasm and the soluble fraction of sonicated homogenates of the livers of rats treated with galactosamine. The activity of phosphoenolpyruvate carboxylase was decreased by 75% of the control value. 6. Glucose synthesis from lactate in perfused livers from galactosamine-treated rats was inhibited 39% when compared with controls. 7. The results indicate that the conversion of lactate into glucose is decreased in the livers of galactosamine-treated rats and that this decrease may be due to the loss of phosphoenolpyruvate carboxylase from damaged hepatocytes.

scholarly journals Metabolic effects of vasopressin infusion in the starved rat. Reversal of ketonaemia

1983 ◽  
Vol 212 (1) ◽  
pp. 231-239 ◽  
Author(s):  
A M Rofe ◽  
D H Williamson
Keyword(s):  
Plasma Insulin ◽  
Ketone Bodies ◽  
Fold Increase ◽  
Metabolic Effects ◽  
Constant Infusion ◽  
Vasopressin Infusion ◽  
Esterified Fatty Acids ◽  
Lactate And Pyruvate ◽  
Blood Ketone Bodies ◽  
Infusion Regimen

The effects of vasopressin on the metabolism of starved rats were investigated by using a constant-infusion regimen (50 pmol/kg body wt. per min, after an initial loading dose of 150 pmol/kg body wt.). 2. Blood ketone bodies decreased by 50% in 10 min, and this was accompanied by a 60% decrease in the plasma non-esterified fatty acids. 3. Blood glucose increased by 0.9 mM within 5 min and decreased to control values over the 40 min infusion. Small increases in lactate and pyruvate also occurred. 4. Plasma insulin was not increased by vasopressin infusion. 5. The net decrease in blood ketone bodies caused by vasopressin was similar when somatostatin was infused simultaneously (1 nmol/kg body wt. per min). 6. Hepatic ketone bodies were significantly decreased by vasopressin, as was the 3-hydroxybutyrate/acetoacetate ratio. A small increase in the hepatic concentration of several glycolytic intermediates also occurred. 7. Vasopressin did not decrease the ketonaemia produced by infusions of octanoate or long-chain triacylglycerol in rats that had been pre-treated with the anti-lipolytic agent 3,5-dimethylpyrazole. 8. In comparison with vasopressin, the infusion of adrenaline or glucose had much smaller effects in decreasing the ketonaemia of starvation, despite the 4-fold increase in plasma insulin, at 10 min, with the glucose infusion. 9. The primary metabolic effect of vasopressin in the starved rat appears to be that of decreased supply of non-esterified fatty acid to the liver. It is suggested that vasopressin has a direct anti-lipolytic effect in adipose tissue.

The Removal of Infused Leucine after Injury, Starvation and other Conditions in Man

1980 ◽  
Vol 59 (4) ◽  
pp. 275-283 ◽  
Author(s):  
M. Elia ◽  
Rose Farrell ◽  
Vera Ilic ◽  
R. Smith ◽  
D. H. Williamson
Keyword(s):  
Muscular Dystrophy ◽  
Blood Concentration ◽  
Ketone Bodies ◽  
Elective Surgery ◽  
Metabolic Effects ◽  
Accidental Injury ◽  
Sufficient Energy ◽  
Branched Chain ◽  
Clinical Conditions ◽  
Basal Concentration

1. To investigate the effects of starvation, elective surgery, accidental injury and other clinical conditions on the metabolism of branched-chain amino acids in man, we have measured the basal concentration of leucine and the removal and metabolic effects of infused l-leucine. 2. The blood concentration of leucine was significantly increased by surgery, starvation and accidental injury, and decreased in cirrhosis. It tended to increase in diabetes and was unaffected by muscular dystrophy. 3. The half-life of infused leucine was nearly doubled by 4 days of complete starvation, unaltered by surgery and decreased by severe accidental injury. Infusion with Intralipid, which increased free fatty acid and ketone-body concentrations, had no effect on the removal of a leucine load. The clearance rate of infused leucine was reduced in diabetes and muscular dystrophy and increased in cirrhosis. 4. The effects of infused leucine on blood glucose and ketone bodies differed according to the groups studied. 5. Since the traumatized patients were given sufficient energy and nitrogen and disposed of a leucine load at a different rate from the starved patients, the causes of the increase in blood concentration of leucine in these two conditions are different.

scholarly journals Vitamin B12 deficiency: metabolic effects, clinical evaluation, and treatment

2019 ◽  
Vol 59 (2) ◽  
pp. 40 ◽  
Author(s):  
Synara Cavalcante Lopes ◽  
Daniel Duarte Gadelha ◽  
Manuela Dias de Carvalho ◽  
Virgínia Oliveira Fernandes ◽  
Renan Magalhães Montenegro Junior
Keyword(s):  
Insulin Resistance ◽  
Vitamin B12 ◽  
Neurological Disorders ◽  
Vitamin B12 Deficiency ◽  
The Body ◽  
Water Soluble ◽  
Metabolic Effects ◽  
Pharmacological Treatments ◽  
B12 Deficiency ◽  
Composition Changes

Vitamin B12 is a water-soluble essential micronutrient, required by all the body cells. Its deficiency has been implicated not only in hematological and neurological disorders, but also in many metabolic processes, such as insulin resistance and body composition changes, which have aroused particular interest in recent years. This study reviews the physiology of vitamin B12 from its digestion and absorption to its distribution in tissues, metabolic effects and controversies regarding the diagnosis of deficiency, and to dietary and pharmacological treatments.

scholarly journals The existence of multiple tetrameric conformers of chicken liver pyruvate carboxylase and their roles in dilution inactivation

1993 ◽  
Vol 290 (2) ◽  
pp. 583-590 ◽  
Author(s):  
P V Attwood ◽  
W Johannssen ◽  
A Chapman-Smith ◽  
J C Wallace
Keyword(s):  
Rate Constants ◽  
Pyruvate Carboxylase ◽  
Electron Microscopic Observation ◽  
Enzyme Concentration ◽  
Enzymic Activity ◽  
Chicken Liver ◽  
Electron Microscopic ◽  
Acetyl Coa ◽  
Degree Of Dissociation ◽  
Tetrameric Structure

The time-dependent loss of enzymic activity and tetrameric structure of chicken liver pyruvate carboxylase (EC 6.4.1.1) after dilution below 2 units/ml was apparently monophasic and first-order. When examined over a range of initial enzyme concentrations, both activity and tetrameric structure decayed to equilibrium levels which were dependent on the initial concentration. The observed rate constants for the loss of enzymic activity (i) showed no apparent dependence on the initial enzyme concentration, and (ii) were of similar magnitude to the corresponding rate constants of dissociation. Computer simulations of the most likely kinetic model suggest that the predominant form of the dissociated enzyme is the monomer. Dilution of pyruvate carboxylase in the presence of the allosteric activator acetyl-CoA largely prevented the subsequent dissociation of the tetrameric molecule. In addition, acetyl-CoA was able to cause a degree of activation and reassociation when added after dilution inactivation had been allowed to occur. Electron-microscopic observation showed the treatment with avidin before dilution markedly decreased the degree of dissociation of the enzyme tetramer. This structure-stabilizing effect of avidin was dependent on preincubation of the concentrated enzyme solution with acetyl-CoA. We propose that, over a range of protein concentrations, the tetrameric enzyme exists in two forms that are in equilibrium, and that acetyl-CoA alters the equilibrium to favour the more compact form.

scholarly journals Pig liver pyruvate carboxylase. Purification, properties and cation specificity

1974 ◽  
Vol 139 (2) ◽  
pp. 297-310 ◽  
Author(s):  
Graham B. Warren ◽  
Keith F. Tipton
Keyword(s):  
Pyruvate Carboxylase ◽  
Monomer Unit ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Liver Mitochondria ◽  
Univalent Cations ◽  
Acetyl Coa ◽  
Pig Liver ◽  
Apparent Homogeneity ◽  
Polypeptide Chains

1. Pyruvate carboxylase was purified to apparent homogeneity from pig liver mitochondria and shown to be free of all kinetically contaminating enzymes. 2. The enzyme has a mol. wt. of 520000 and is composed of four subunits, each with a mol. wt. of 130000. 3. The enzyme can exist as the active tetramer, dimer and monomer, although the tetramer appears to be the form in which the enzyme is normally assayed. 4. For every 520000g of the enzyme there are 4mol of biotin, 3mol of zinc and 1mol of magnesium. No significant concentrations of manganese were detected. 5. Analysis by sodium dodecyl sulphate–polyacrylamide gel electrophoresis indicates three polypeptide chains per monomer unit, each with a mol. wt. of 47000. 6. The amino acid analysis, stoicheiometry of the reaction and the activity of the enzyme as a function of pH are also presented. 7. The enzyme is activated by a variety of univalent cations but not by Tris+ or triethanolamine+. 8. The activity of the enzyme is dependent on the presence of acetyl-CoA; the low rate in the absence of added acetyl-CoA is not due to an enzyme-bound acyl-CoA. The dissociation constant for enzyme-bound acetyl-CoA is a marked function of pH.

scholarly journals Metabolic effects of vitamin B12 on physiology, stress resistance, growth rate and biomass productivity of Cyanobacterium stanieri planktonic and biofilm cultures

2019 ◽  
Vol 42 ◽  
pp. 101580
Author(s):  
Pavlo Bohutskyi ◽  
Ryan S. McClure ◽  
Eric A. Hill ◽  
William C. Nelson ◽  
William B. Chrisler ◽  
...  
Keyword(s):  
Growth Rate ◽  
Vitamin B12 ◽  
Stress Resistance ◽  
Biomass Productivity ◽  
Metabolic Effects

scholarly journals A Clinical Case of Clozapine-Induced Fatal Diabetic Ketoacidosis

2016 ◽  
Vol 7 ◽  
pp. CMPsy.S30532
Author(s):  
Eric Romney ◽  
Vinay J. Nagaraj ◽  
Amie Kafer
Keyword(s):  
Fatty Acids ◽  
Weight Gain ◽  
Free Fatty Acids ◽  
Diabetic Ketoacidosis ◽  
Ketone Bodies ◽  
Pancreatic Beta Cell ◽  
Metabolic Effects ◽  
Psychotic Symptoms ◽  
Life Threatening ◽  
Altered Metabolism

Introduction Clozapine, a second generation medication, has become the atypical antipsychotic drug of choice for refractory or treatment-resistant schizophrenia. In addition to the high risk of agranulocytosis and seizures, clozapine treatment is increasingly associated with significant metabolic effects, such as hyperglycemia, central weight gain and adiposity, hypertriglyceridemia, and elevated low-density lipoprotein cholesterol. A potentially life-threatening complication of altered metabolism is diabetic ketoacidosis (DKA). This report details a case of fatal DKA in a schizophrenic patient undergoing treatment with clozapine. Case Description An African–American male in his 20s with a medical history significant for schizophrenia was presented to the psychiatric inpatient ward with severe paranoid thoughts and aggressive behavior. After trials of risperidone, olanzapine, and haloperidol—all of which failed to adequately control his psychotic symptoms—clozapine titration was initiated and he showed significant improvement. Weight gain was observed throughout hospitalization, but all blood and urine test results showed no metabolic or hematological abnormalities. The patient was discharged for outpatient treatment on clozapine (125 mg morning and 325 mg evening) along with divalproex sodium and metoprolol. Six days post-discharge, the patient died. A medical autopsy later ruled that the death was due to DKA without any evidence of contributory injuries or natural disease. Results and Conclusion Significant increase in body mass index from 28.7 to 33.5 was observed during hospitalization. The blood glucose level, measured after his death, was found to be 500 mg/dL. Altered metabolism due to clozapine can lead to dyslipidemia-mediated-pancreatic-beta-cell damage, decreased insulin secretion as well as insulin resistance. In DKA, low levels of insulin lead to an increased release of free fatty acids from adipose tissue. Acetyl coenzyme A (CoA), derived from the breakdown of free fatty acids, is metabolized by the Kreb's cycle. In hepatocytes, excess acetyl-CoA is converted into ketone bodies (acetoacetate and β-hydroxybutyrate) and released into circulation. Ketone bodies have a low p Ka value and their high serum concentrations lead to DKA. In this patient, DKA was most probably clozapine induced and had fatal consequences. Thus, recognizing potential risk factors, providing patient education, and increasing monitoring of patients on clozapine and other atypical antipsychotics are critical to prevent the life-threatening effects of DKA.

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