Conversion of inactive (phosphorylated) pyruvate dehydrogenase complex into active complex by the phosphatase reaction in heart mitochondria is inhibited by alloxan-diabetes or starvation in the rat

1978 ◽  
Vol 175 (3) ◽  
pp. 769.b1-769.b1
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Alloxan Diabetes ◽  
Pyruvate Dehydrogenase Complex ◽  
Heart Mitochondria ◽  
Active Complex ◽  
Dehydrogenase Complex

scholarly journals Conversion of inactive (phosphorylated) pyruvate dehydrogenase complex into active complex by the phosphate reaction in heart mitochondria is inhibited by alloxan-diabetes or starvation in the rat

1978 ◽  
Vol 173 (2) ◽  
pp. 669-680 ◽  
Author(s):  
N J Hutson ◽  
A L Kerbey ◽  
P J Randle ◽  
P H Sugden
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Rat Heart ◽  
Pyruvate Dehydrogenase Complex ◽  
Diabetic Rats ◽  
Atp Depletion ◽  
Heart Mitochondria ◽  
Active Complex ◽  
Phosphate Complex ◽  
Rat Hearts ◽  
Dehydrogenase Complex

1. The conversion of inactive (phosphorylated) pyruvate dehydrogenase complex into active (dephosphorylated) complex by pyruvate dehydrogenase phosphate phosphatase is inhibited in heart mitochondria prepared from alloxan-diabetic or 48h-starved rats, in mitochondria prepared from acetate-perfused rat hearts and in mitochondria prepared from normal rat hearts incubated with respiratory substrates for 6 min (as compared with 1 min). 2. This conclusion is based on experiments with isolated intact mitochondria in which the pyruvate dehydrogenase kinase reaction was inhibited by pyruvate or ATP depletion (by using oligomycin and carbonyl cyanide m-chlorophenylhydrazone), and in experiments in which the rate of conversion of inactive complex into active complex by the phosphatase was measured in extracts of mitochondria. The inhibition of the phosphatase reaction was seen with constant concentrations of Ca2+ and Mg2+ (activators of the phosphatase). The phosphatase reaction in these mitochondrial extracts was not inhibited when an excess of exogenous pig heart pyruvate dehydrogenase phosphate was used as substrate. It is concluded that this inhibition is due to some factor(s) associated with the substrate (pyruvate dehydrogenase phosphate complex) and not to inhibition of the phosphatase as such. 3. This conclusion was verified by isolating pyruvate dehydrogenase phosphate complex, free of phosphatase, from hearts of control and diabetic rats an from heart mitochondria incubed for 1min (control) or 6min with respiratory substrates. The rates of re-activation of the inactive complexes were then measured with preparations of ox heart or rat heart phosphatase. The rates were lower (relative to controls) with inactive complex from hearts of diabetic rats or from heart mitochondria incubated for 6min with respiratory substrates. 4. The incorporation of 32Pi into inactive complex took 6min to complete in rat heart mitocondria. The extent of incorporation was consistent with three or four sites of phosphorylation in rat heart pyruvate dehydrogenase complex. 5. It is suggested that phosphorylation of sites additional to an inactivating site may inhibit the conversion of inactive complex into active complex by the phosphatase in heart mitochondria from alloxan-diabetic or 48h-starved rats or in mitochondria incubated for 6min with respiratory substrates.

scholarly journals Proportion of active dephosphorylated pyruvate dehydrogenase complex in heart and isolated heart mitochondria is decreased in obese hyperinsulinaemic mice

1984 ◽  
Vol 217 (1) ◽  
pp. 117-121 ◽  
Author(s):  
A L Kerbey ◽  
I D Caterson ◽  
P F Williams ◽  
J R Turtle
Keyword(s):  
Insulin Resistance ◽  
Enzyme Activity ◽  
Pyruvate Dehydrogenase ◽  
Glucose Oxidation ◽  
Isolated Heart ◽  
Pyruvate Dehydrogenase Complex ◽  
Heart Mitochondria ◽  
Mouse Heart ◽  
Inhibitory Effects ◽  
Dehydrogenase Complex

The proportion of active, dephosphorylated, pyruvate dehydrogenase complex was decreased in the mouse heart by obesity (by 56%), and this decrease in enzyme activity persisted during preparation and extraction of heart mitochondria. Phosphorylation and inactivation of pyruvate dehydrogenase may be a major factor in mediating the inhibitory effects of obesity on glucose oxidation in muscle, and this may represent an important mechanism in the development and/or expression of cellular insulin-resistance.

scholarly journals Effect of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid on pyruvate dehydrogenase complex activity in starved and alloxan-diabetic rats

1982 ◽  
Vol 208 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Ian D. Caterson ◽  
Stephen J. Fuller ◽  
Philip J. Randle
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Pyruvate Dehydrogenase ◽  
Heart Muscle ◽  
Alloxan Diabetes ◽  
Pyruvate Dehydrogenase Complex ◽  
Diabetic Rats ◽  
Acid Oxidation ◽  
Active Complex ◽  
Perfused Hearts

Intravenous administration of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid had no effect on the proportion of pyruvate dehydrogenase complex in the active form in heart, diaphragm or gastrocnemius muscles or in liver, kidney or adipose tissue of fed normal rats. The compound reversed the effect of 48h starvation (which decreased the proportion of active complex) in heart muscle, partially reversed the effect of starvation in kidney, but had no effect in the other tissues listed. The compound failed to reverse the effect of alloxan-diabetes (which decreased the proportion of active complex) in any of these tissues. In perfused hearts of fed normal rats, 2-tetradecylglycidate reversed effects of palmitate (which decreased the proportion of active complex), but it had no effect in the absence of palmitate. In perfused hearts of 48h-starved rats the compound increased the proportion of active complex to that found in fed normal rats in the presence or absence of insulin. In perfused hearts of diabetic rats the compound normalized the proportion of active complex in the presence of insulin, but not in its absence. Palmitate reversed the effects of 2-tetradecylglycidate in perfused hearts of starved or diabetic rats. Evidence is given that 2-tetradecylglycidate only reverses effects of starvation and alloxan-diabetes on the proportion of active complex in heart muscle under conditions in which it inhibits fatty acid oxidation. It is concluded that effects of starvation and alloxan-diabetes on the proportion of active complex in heart muscle are dependent on fatty acid oxidation. Insulin had no effect on the proportion of active complex in hearts or diaphragms of fed or starved rats in vitro. In perfused hearts of alloxan-diabetic rats, insulin induced a modest increase in the proportion of active complex in the presence of albumin, but not in its absence.

Effect of sepsis on activity of pyruvate dehydrogenase complex in skeletal muscle and liver

1986 ◽  
Vol 250 (6) ◽  
pp. E634-E640 ◽  
Author(s):  
T. C. Vary ◽  
J. H. Siegel ◽  
T. Nakatani ◽  
T. Sato ◽  
H. Aoyama
Keyword(s):  
Skeletal Muscle ◽  
Pyruvate Dehydrogenase ◽  
Concentration Ratio ◽  
Coenzyme A ◽  
Pyruvate Dehydrogenase Complex ◽  
Sterile Inflammation ◽  
Active Complex ◽  
Small Abscess ◽  
Dehydrogenase Complex ◽  
Large Abscess

The effect of chronic sepsis on the concentration of active pyruvate dehydrogenase complex has been investigated in liver and skeletal muscle of normal, sterile inflammatory, and chronic septic (small and large abscess) animals. Hyperdynamic sepsis was induced by the intraperitoneal introduction of a rat fecal-agar pellet of known size and bacterial composition (Escherichia coli + Bacteroides fragilis). Total pyruvate dehydrogenase complex activity was not altered in either liver or skeletal muscle in any of the conditions studied. In hepatic tissue, sterile inflammation increased the proportion of active complex 2.5-fold compared with control. The same increase in the concentration of active complex was observed in animals with a small abscess. When the abscess size was increased (large abscess), the concentration of active complex was decreased relative to sterile inflammatory or small abscess septic animals. In contrast to liver, sterile inflammation did not alter the proportion of active complex in skeletal muscle. Sepsis (either small or large septic abscess) resulted in threefold decrease in the concentration of active complex relative to control or sterile inflammatory animals. Changes in the concentration of active complex did not appear to be dependent on the ATP/ADP concentration ratio or tissue pyruvate levels but were consistent with changes in the acetyl-coenzyme A-to-coenzyme A concentration ratio. The mechanism responsible for altered concentration of active complex may be mediated through changes in the activity of the pyruvate dehydrogenase kinase, secondary to alterations in the effector concentration ratios.

scholarly journals Incorporation of [32P]phosphate into the pyruvate dehydrogenase complex in rat heart mitochondria

1980 ◽  
Vol 188 (2) ◽  
pp. 409-421 ◽  
Author(s):  
G J Sale ◽  
P J Randle
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Rat Heart ◽  
Pyruvate Dehydrogenase Complex ◽  
Diabetic Rats ◽  
Heart Mitochondria ◽  
Kinase Reaction ◽  
Rat Heart Mitochondria ◽  
Dehydrogenase Complex

1. Evidence is given for three sites of phosphorylation in the alpha-chains of the decarboxylase component of purified rat heart pyruvate dehydrogenase complex, analogous to those established for procine and bovine complexes. Inactivation of rat heart complex was correlated with phosphorylation of site 1. Relative initial rates of phosphorylation were site 1 greater than site 2 greater than site 3. 2. Methods are described for measurement of incorporation of 32Pi into the complex in rat heart mitochondria oxidizing 2-oxoglutarate + L-malate (total, sites 1, 2 and 3). Inactivation of the complex was related linearly to phosphorylation of site 1 in mitochondria of normal or diabetic rats. The relative initial rates of phosphorylation were site 1 greater than site 2 greater than site 3. Rates of site-2 and site-3 phosphorylation may have been closer to that of site 1 in mitochondria of diabetic rats than in mitochondria of normal rats. 3. The concentration of inactive (phosphorylated) complex was varied in mitochondria from normal rats by inhibiting the kinase reaction with pyruvate at concentrations ranging from 0.15 to 0.4 mM. The results showed that the concentration of inactive complex is related linearly to incorporation of 32Pi into site 1. Inhibition of 32Pi incorporations with pyruvate at all concentrations over this range was site 3 greater than site 2 greater than site 1. 4. With mitochondria from diabetic rats, pyruvate (0.15-0.4 mM) inhibited incorporation of 32Pi into site 3, but it had no effect on the concentration of inactive complex or on incorporations of 32Pi into site 1 or site 2. It is concluded that site-3 phosphorylation is not required for inactivation of the complex in rat heart mitochondria. 5. Evidence is given that phosphorylation of sites 2 and 3 may inhibit reactivation of the complex by dephosphorylation in rat heart mitochondria.

scholarly journals The effect of a water-soluble vitamins on the activity of some enzymes in diabetes

2014 ◽  
Vol 60 (6) ◽  
pp. 623-630
Author(s):  
S.A. Petrov ◽  
A.O. Danilova ◽  
L.M. Karpov
Keyword(s):  
Ascorbic Acid ◽  
Folic Acid ◽  
Pyruvate Dehydrogenase ◽  
Alloxan Diabetes ◽  
Pyruvate Dehydrogenase Complex ◽  
Water Soluble ◽  
Calcium Pantothenate ◽  
Pyridoxine Hydrochloride ◽  
Enzymes Of Energy Metabolism ◽  
Dehydrogenase Complex

Intramuscular injections of the vitamin complex containing: thiamine chloride (B1), riboflavin (B2), lipoic acid (N), calcium pantothenate (B5), pyridoxine hydrochloride (B6), folic acid (B9), ascorbic acid (C) can reduce the blood glucose level in serum of rats with alloxan diabetes, stabilize activity of some enzymes of energy metabolism, lactate dehydrogenase and pyruvate dehydrogenase complex.

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