Studies on the rapid stimulation of mitochondrial respiration by thyroid hormones

1992 ◽  
Vol 127 (6) ◽  
pp. 542-546 ◽  
Author(s):  
Ian O'Reilly ◽  
Michael P Murphy
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Mitochondrial Respiration ◽  
Liver Mitochondria ◽  
Respiration Rates ◽  
Iodothyronine Deiodinases ◽  
Rapid Stimulation ◽  
Isolated Liver ◽  
Cytoplasmic Ribosomes ◽  
Stimulation Of

Injection of L-3,5-diiodothyronine (T2) into rats made hypothyroid by 6-n-propyl-2-thiouracil (PTU) increased the respiration rates of subsequently isolated liver mitochondria; this stimulation of respiration by T2 occurred in the presence of cycloheximide and is therefore independent of protein synthesis on cytoplasmic ribosomes. Injection of T3 into PTU-treated rats had a lesser effect than T2 on the respiration rates of subsequently isolated mitochondria; as PTU is an inhibitor of 5′-iodothyronine deiodinases, which convert T3 into T2 in vivo, the rapid stimulation of mitochondrial respiration by T3, which has been shown in a range of systems, may not be due directly to T3 itself, but may be mediated by its deiodination product T2. Injection of T2, or T3, into hypothyroid or euthyroid rats had no effect on the percentage activity of mitochondrial pyruvate hydrogenase assayed 30 min later. The amount of active pyruvate dehydrogenase is regulated by changes in mitochondrial calcium concentration and matrix ATP/ADP ratio; therefore these parameters are not persistently affected by treatment with T3 or T2. In addition, the total amount of pyruvate dehydrogenase present was the same in euthyroid and hypothyroid rats, indicating that the expression of this enzyme is not stringently controlled by thyroid hormone status.

scholarly journals Evidence that the stimulation of lipogenesis in the mammary glands of starved lactating rats re-fed with a chow diet is dependent on continued hepatic gluconeogenesis during the absorptive period. Effects of a gluconeogenic inhibitory, mercaptopicolinic acid, in vivo

1985 ◽  
Vol 228 (3) ◽  
pp. 727-733 ◽  
Author(s):  
D H Williamson ◽  
V Ilic ◽  
R G Jones
Keyword(s):  
Mammary Gland ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Mammary Glands ◽  
Hepatic Glycogen ◽  
Chow Diet ◽  
Hepatic Gluconeogenesis ◽  
Rapid Stimulation ◽  
Stimulation Of

The rapid stimulation of lipogenesis in mammary gland that occurs on re-feeding starved lactating rats with a chow diet was decreased (60%) by injection of mercaptopicolinic acid, an inhibitor of hepatic gluconeogenesis at the phosphoenolpyruvate carboxykinase step. Mercaptopicolinate had no effect on lipogenesis in mammary glands of fed lactating rats. The inhibition of lipogenesis persisted in vitro when acini from mammary glands of re-fed rats treated with mercaptopicolinate were incubated with [1-14C]glucose. Mercaptopicolinate added in vitro had no significant effect on lipogenesis in acini from starved-re-fed lactating rats. Mercaptopicolinate prevented the deposition of glycogen and increased the rate of lipogenesis in livers of starved-re-fed lactating rats, whereas it had no significant effect on livers of fed lactating rats. Administration of intraperitoneal glucose restored the rate of mammary-gland lipogenesis in re-fed rats treated with mercaptopicolinate to the values for re-fed rats. Hepatic glycogen deposition was also restored, and the rate of hepatic lipogenesis was stimulated 5-fold. It is concluded that stimulation of mammary-gland lipogenesis on re-feeding with a chow diet after a period of starvation is in part dependent on continued hepatic gluconeogenesis during the absorptive period. Possible sources of the glucose precursors are discussed.

scholarly journals Stimulation of the respiration rate of rat liver mitochondria by sub-micromolar concentrations of extramitochondrial Ca2+

1987 ◽  
Vol 245 (1) ◽  
pp. 217-222 ◽  
Author(s):  
J D Johnston ◽  
M D Brand
Keyword(s):  
Respiration Rate ◽  
Rat Liver ◽  
Oxidative Metabolism ◽  
Mitochondrial Respiration ◽  
Liver Mitochondria ◽  
Ruthenium Red ◽  
Rat Liver Mitochondria ◽  
Mitochondrial Matrix ◽  
Stimulation Of

1. The respiration rate of rat liver mitochondria was stimulated by up to 70% when the extramitochondrial Ca2+ concentration was raised from 103 to 820 nM. This occurred when pyruvate, 2-oxoglutarate, or threo-(Ds)-isocitrate was employed as substrate, but not when succinate was used. 2. Ruthenium Red prevented the stimulation of mitochondrial respiration by extramitochondrial Ca2+, showing that the effect required Ca2+ uptake into the mitochondrial matrix. 3. Starvation of rats for 48 h abolished the stimulation of mitochondrial respiration by extramitochondrial Ca2+ when pyruvate was used as substrate, but did not affect the stimulation of 2-oxoglutarate oxidation by extramitochondrial Ca2+. 4. Our findings are in accord with proposals that oxidative metabolism in liver mitochondria may be stimulated by Ca2+ activation of intramitochondrial dehydrogenases.

scholarly journals Studies on the activation of rat liver pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase by adrenaline and glucagon. Role of increases in intramitochondrial Ca2+ concentration

1985 ◽  
Vol 231 (3) ◽  
pp. 597-608 ◽  
Author(s):  
J G McCormack
Keyword(s):  
Rat Liver ◽  
Pyruvate Dehydrogenase ◽  
Liver Mitochondria ◽  
Active Enzyme ◽  
Female Rats ◽  
Rat Liver Mitochondria ◽  
Na Ions ◽  
Oxoglutarate Dehydrogenase

The administration in vivo of either adrenaline or glucagon alone resulted in increases of about 2-fold in the amounts of active, non-phosphorylated, pyruvate dehydrogenase in the livers of fed male or female rats, whereas when administered together increases of about 4-fold were obtained. Ca2+-dependent increases in the amount of active enzyme of up to about 5-fold could be achieved in isolated rat liver mitochondria by incubating them with increasing extramitochondrial [Ca2+]; from this, two conditions of Ca loading were chosen which caused increases in active enzyme similar to those with the hormone treatments given above. The increases in enzyme activity owing to these Ca loads persisted through the ‘re-isolation’ of mitochondria and their incubation in Na+-free KCl-based media containing EGTA. Differences from values obtained with unloaded controls could be diminished by adding Na+ ions to cause the egress of Ca2+ from the mitochondria, or enough extramitochondrial Ca2+ to saturate the enzyme in its Ca2+-dependent activation; the effects of Na+ could be blocked by diltiazem, an inhibitor of mitochondrial Na+/Ca2+ exchange. The re-isolated, Ca-preloaded, mitochondria also exhibited enhanced activities of 2-oxoglutarate dehydrogenase when assayed at non-saturating [2-oxoglutarate] by two different methods; effects of Na+, Ca2+ or diltiazem on the persistent activations of this enzyme were similar to those for pyruvate dehydrogenase. Na+ caused a marked depletion, which could be blocked by diltiazem, of the 45Ca content of re-isolated mitochondria which had pre-loaded with Ca, containing 45Ca, to the same degrees as above. The activities of pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase in incubated liver mitochondria prepared from rats subjected to the hormone treatments given above were found to behave in a very similar manner to those exhibited in the re-isolated, Ca-preloaded, mitochondria. It is concluded that these hormones each bring about the activations of these rat liver enzymes by causing increases in intramitochondrial [Ca2+], and that their effects, as such, are additive.

scholarly journals Effects of glucagon and N6O2′-dibutyryladenosine 3′:5′-cyclic monophosphate on calcium transport in isolated rat liver mitochondria

1978 ◽  
Vol 176 (1) ◽  
pp. 295-304 ◽  
Author(s):  
B P Hughes ◽  
G J Barritt
Keyword(s):  
Retention Time ◽  
Calcium Transport ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Dibutyryl Cyclic Amp ◽  
Oxygen Utilization ◽  
Isolated Rat Liver ◽  
Isolated Mitochondria ◽  
Isolated Liver ◽  
Stimulation Of

1. The administration of glucagon to fed rats by intraperitoneal injection, or the perfusion of livers from fed rats with glucagon by the method of Mortimore [Mortimore (1963) Am.J. Physiol. 204, 699–704] was associated with increases of 15- and 5-fold respectively, in the time for which a given load of exogenous Ca2+ is retained by mitochondria subsequently isolated from the liver. This effect of glucagon was (a) also induced by N6O2′-dibutyryl cyclic AMP, (b) completely blocked by cycloheximide, (c) relatively slow in onset (15–60 min) and (d) associated with a stimulation of about 20% in the rates of ADP-stimulated oxygen utilization and Ca2+ transport measured in the presence of succinate. 2. Perfusion of livers with glucagon resulted in the isolation of mitochandria which showed a 50% increase, no significant change and a 40% increase in the concentrations of endogenous Ca, Mg and Pi respectively, when compared with mitochondria isolated from control perfused livers. 3. The administration of insulin or adrenaline to fed rats induced increases of 10- and 8-fold respectively, in the time for which Ca2+ is retained by isolated liver mitochondria. Perfusion of livers with insulin had no effect on mitochondrial Ca2+ retention time. 4. The perfusion of livers from starved rats with glucagon, or the administration of either glucagon or insulin to starved rats, increased by about 2.5- and 15-fold respectively, the time for which isolated mitochondria retain Ca2+. 5. Mechanisms which may be responsible for the observed alterations in Ca2+-retention time are discussed.

scholarly journals Modulation of pyruvate dehydrogenase kinase activity in cultured hepatocytes by glucagon and n-octanoate

1986 ◽  
Vol 234 (1) ◽  
pp. 233-236 ◽  
Author(s):  
H R Fatania ◽  
T C Vary ◽  
P J Randle
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Chain Complex ◽  
Rat Hepatocytes ◽  
Liver Mitochondria ◽  
Pyruvate Dehydrogenase Kinase ◽  
Rat Liver Mitochondria ◽  
Potential Contribution ◽  
Complex Activity ◽  
Branched Chain

The activity of pyruvate dehydrogenase kinase in extracts of mitochondria from rat hepatocytes cultured for 21 h in medium 199 was increased 2.5-fold by the presence of 55 nM-glucagon and 1 mM-sodium n-octanoate in the culture medium. The change was comparable with that induced in vivo by 48 h starvation. The potential contribution of branched-chain complex to estimates of PDH-complex activity in rat liver mitochondria has been defined.

Stimulation of flux through hepatic pyruvate dehydrogenase by 3-mercaptopicolinate

1984 ◽  
Vol 4 (5) ◽  
pp. 441-450 ◽  
Author(s):  
David D. Myles ◽  
Peter Strong ◽  
Garry D. Stratton ◽  
Ian F. Skidmore ◽  
Mary C. Sugden
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Blood Glucose Concentration ◽  
Tricarboxylic Acid Cycle ◽  
Pyruvate Dehydrogenase Complex ◽  
Isolated Hepatocytes ◽  
Blood Concentrations ◽  
Decrease Blood Glucose ◽  
Hypoglycaemic Agent ◽  
Stimulation Of

Isolated hepatocytes from 24-h-starved rats were used to assess the possible effect of Ahe hypoglycaemic agent 3-mercaptopicolinate on flux through the hepatic pyruvate dehydrogenase complex. Increasing the extraceIIular pyruvate concentration from 1 mM to 2 mM or 5 mM resulted in an increase in flux through pyruvate dehydrogenase and the tricarboxylic acid cycle as measured by14CO2 evolution from [1-14C]pyruvate and [3-14C]pyruvate. Gluconeogenesis was inhibited by 3-mercaptopicolinate from both 1 mM and 2 mM pyruvate, but significant increases in malate and citrate concentrations only occurred in cells incubated with 1 mM pyruvate. Flux through pyruvate dehydrogenase was stimulated by 3-mercaptopicolinate with 1 mM pyruvate but was unaltered with 2 mM pyruvate. Dichloroacetate stimulated flux through pyruvate dehydrogenase with no effect on gluconeogenesis in the presence of I mM pyruvate. There was no effect of 3-mercaptopicolinate, administered in vivo, to 24-h-starved rats on the activity of pyruvate dehydrogenase in freeze-clamped heart or liver tissue, although the drug did decrease blood glucose concentration and increase the blood concentrations of lactate and alanine. Dichloroacetate, administered in vivo to 24-h-starved rats, increased the activity of pyruvate dehydrogenase in freeze-clamped heart and liver, and caused decreases in the blood concentrations of glucose, lactate, and alanine. The results suggest that 3-mercaptopicolinate increases flux through hepatocyte pyruvate dehydrogenase by an indirect mechanism.

scholarly journals The cell-free synthesis of cytochrome c by a microsomal fraction from rat liver

1971 ◽  
Vol 124 (4) ◽  
pp. 685-694 ◽  
Author(s):  
Néstor F. González-Cadavid ◽  
Juan P. Ortega ◽  
Magally González
Keyword(s):  
Cytochrome C ◽  
Microsomal Fraction ◽  
Freezing And Thawing ◽  
Prosthetic Group ◽  
Extraction And Purification ◽  
Isolated Liver ◽  
Cytoplasmic Ribosomes ◽  
Homogenization Medium

Conditions were investigated for demonstrating the synthesis in vitro of the complete molecule of cytochrome c by isolated liver microsomal systems from partially hepatectomized rats. It was first found that in vivo the early labelled cytochrome c associated with the microsomal fraction required, by comparison with the mitochondrial pool, more drastic conditions of extraction and its binding was less affected by freezing and thawing of the subcellular particles. The procedure of extraction and purification of cytochrome c had to be modified accordingly, to assure the recovery of the recently synthesized molecule. Several subcellular fractions were isolated from regenerating liver with a homogenization medium containing either 5 or 10mm-Mg2+ and most of them were active in the synthesis of the cytochrome c apoprotein. The microsomal fraction, in the presence of either cell sap or pH5.0 fraction, was also able to incorporate [59Fe]haemin, δ-amino[3H]laevulic acid and 55Fe into the prosthetic group of cytochrome c. These experiments confirm firmly the conclusions of our previous results obtained in vivo showing that both the apoprotein and the haem moieties are made and linked together on cytoplasmic ribosomes and only then is the complete molecule transferred to the mitochondria.

scholarly journals Regulation of glycine catabolism in rat liver mitochondria

1992 ◽  
Vol 283 (2) ◽  
pp. 435-439 ◽  
Author(s):  
M Jois ◽  
H S Ewart ◽  
J T Brosnan
Keyword(s):  
Rat Liver ◽  
Fold Increase ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Mitochondrial Matrix ◽  
Isolated Rat Liver ◽  
Matrix Volume ◽  
Isolated Rat ◽  
Stimulation Of

1. The catabolism of glycine was studied in isolated rat liver mitochondria by measuring release of 14CO2 from [1-14C]-glycine. Incubation of mitochondria in a medium containing 0.5 microM free Ca2+ resulted in an 8-fold increase in the rate of degradation of glycine. Intraperitoneal injection of glucagon (33 or 100 micrograms/100 g body wt.) 25 min before killing of rats also resulted in a 3-fold or 10-fold (depending on dosage) increase in the rate of catabolism of glycine. 2. Both the stimulation by free Ca2+ and that by injection of glucagon in vivo were dependent on phosphate in the incubation medium. This requirement for phosphate was specific, as replacement of phosphate by other permeant anions such as thiocyanate and acetate did not permit the stimulation. The phosphate-dependent stimulation of glycine catabolism by Ca2+ was also evident when mitochondria were incubated in the absence of K+. 3. Mitochondria isolated from rats previously injected with glucagon showed elevated rates of degradation of glycine even in the presence of rotenone, provided that regeneration of NAD+ was affected by providing acetoacetate. 4. Hypo-osmolarity of the medium markedly stimulated the rate of degradation of glycine by mitochondria. Although hypo-osmolarity-induced stimulation of glycine degradation was accompanied by parallel changes in mitochondrial matrix volume, no measurable changes in matrix volume were observed in mitochondria stimulated either by free Ca2+ (0.5 microM) or by injection of glucagon in vivo. Furthermore, Ca2+ stimulated glycine decarboxylation in mitochondria exposed to either hyper-osmolar (410 mosmol) or hypo-osmolar (210 mosmol) conditions. Although hyper-osmolarity decreased and hypo-osmolarity increased matrix volume, stimulation of glycine degradation by Ca2+ was not associated with any further changes in matrix volume. 5. These data demonstrate that the regulation of hepatic glycine oxidation by glucagon and by free Ca2+ is largely independent of changes in mitochondrial matrix volume.

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