scholarly journals Pyruvate and ketone-body transport across the mitochondrial membrane. Exchange properties, pH-dependence and mechanism of the carrier

1978 ◽  
Vol 172 (3) ◽  
pp. 377-387 ◽  
Author(s):  
A P Halestrap
Keyword(s):  
Mitochondrial Membrane ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Ph Dependence ◽  
Physiological Regulation ◽  
First Order Kinetics ◽  
Sh Group ◽  
Km Value ◽  
The Difference

The effects of exchangeable ions and pH on the efflux of pyruvate from preloaded mitochondria are reported. Efflux obeys first-order kinetics, and the stimulation of efflux by exchangeable ions such as acetoacetate and lactate obeys Michaelis–Menten kinetics. The apparent Km value +/- S.E. for acetoacetate was 0.56 +/- 0.14 mM (n = 5) and that for lactate 12.3 +/- 2.3 mM (n = 6). The Vmax. values +/- S.E. at 0 degrees C were 16.2 +/- 2.0 and 21.9 +/- 2.7 nmol/min per mg of protein. The exchange of a variety of other substituted monocarboxylates was also studied. Efflux was also stimulated by increasing the external pH. The data gave a pK for the transport process of 8.35 and a Vmax. of 3.31 +/- 0.14 nmol/min per mg. The similarity of the Vmax. values for various exchangeable ions but the difference of this from the Vmax. in the absence of exchangeable ions may indicate that transport of pyruvate occurs with H+ and not in exchange for an OH- ion. The inhibition of transport by alpha-cyano-4-hydroxycinnamate took several seconds to reach completion at 0 degrees C. It is proposed that inhibition occurs by binding to the substrate site and subsequent reaction with an -SH group on the inside of the membrane. The inhibitor can be displaced by substrates that can also enter the mitochondria independently of the carrier and so compete with the inhibitor for the substrate-binding site on the inside of the membrane. A mechanism for transport is proposed that invokes a transition state of pyruvate involving addition of an -SH group to the 2-carbon of pyruvate. Evidence is presented that suggests that ketone bodies may cross the mitochondrial membrane either on the carrier or by free diffusion. The physiological involvement of the carrier in ketone-body metabolism is discussed. The role of ketone bodies and pH in the physiological regulation of pyruvate transport is considered.

scholarly journals Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice

2016 ◽  
Vol 310 (2) ◽  
pp. E103-E115 ◽  
Author(s):  
Lionel Carneiro ◽  
Sarah Geller ◽  
Xavier Fioramonti ◽  
Audrey Hébert ◽  
Cendrine Repond ◽  
...  
Keyword(s):  
Food Intake ◽  
Ketone Body ◽  
Energy Homeostasis ◽  
Ketone Bodies ◽  
Glucose Production ◽  
Body Level ◽  
Homeostasis Regulation ◽  
The Impact ◽  
Body Concentration

Monocarboxylates have been implicated in the control of energy homeostasis. Among them, the putative role of ketone bodies produced notably during high-fat diet (HFD) has not been thoroughly explored. In this study, we aimed to determine the impact of a specific rise in cerebral ketone bodies on food intake and energy homeostasis regulation. A carotid infusion of ketone bodies was performed on mice to stimulate sensitive brain areas for 6 or 12 h. At each time point, food intake and different markers of energy homeostasis were analyzed to reveal the consequences of cerebral increase in ketone body level detection. First, an increase in food intake appeared over a 12-h period of brain ketone body perfusion. This stimulated food intake was associated with an increased expression of the hypothalamic neuropeptides NPY and AgRP as well as phosphorylated AMPK and is due to ketone bodies sensed by the brain, as blood ketone body levels did not change at that time. In parallel, gluconeogenesis and insulin sensitivity were transiently altered. Indeed, a dysregulation of glucose production and insulin secretion was observed after 6 h of ketone body perfusion, which reversed to normal at 12 h of perfusion. Altogether, these results suggest that an increase in brain ketone body concentration leads to hyperphagia and a transient perturbation of peripheral metabolic homeostasis.

Modification of Na+/H+ Exchanger in Human Platelets by 1,2-Dioctanoylglycerol, a Protein Kinase C Activator

1990 ◽  
Vol 64 (01) ◽  
pp. 165-171 ◽  
Author(s):  
Yukio Ozaki ◽  
Yuki Mastsumoto ◽  
Yutaka Yatomi ◽  
Masaaki Higashihara
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Rate Constant ◽  
Human Platelets ◽  
Kinase C ◽  
Km Value ◽  
The Difference ◽  
The One ◽  
Protein Kinase C Activation

SummaryProtein kinase C activation in human platelets has a modulatory role in maintaining intracellular pH (pHi), by adjusting pHi at a particular value (7.22). Changes in pHi induced by protein kinase C appeared to be dependent upon the difference between H+ efflux catalyzed by the Na+/H+ exchanger and H+ production. The pHi recovery after acid loading was significantly facilitated by protein kinase C activation. Analysis of the rate constant for pHi recovery suggested that the turnover rate or the apparent affinity of the Na+/H+ exchanger for H+ was increased. Protein kinase C also decreased the Km value of the Na+/H+ exchanger for extracellular Na+. Thus, it is suggested that the role of protein kinase C in platelet pHi regulation is dual, adjusting the pHi value at a certain setpoint on the one hand, and increasing the rate constant of the Na+/H+ exchanger on the other.

Contribution to the knowledge of the role of SH-groups in the molecule of pea alcohol dehydrogenase

1985 ◽  
Vol 50 (9) ◽  
pp. 2015-2020
Author(s):  
Noemi Čeřovská ◽  
Sylva Leblová
Keyword(s):  
Alcohol Dehydrogenase ◽  
Active Center ◽  
Protective Action ◽  
First Order ◽  
Sh Groups ◽  
Coenzyme Binding ◽  
First Order Kinetics ◽  
Sh Group ◽  
Pea Seeds

p-Chloromercuribenzoate irreversibly inactivates alcohol dehydrogenase (ADH) isolated from germinating pea seeds. The reaction follows the first order kinetics. The inactivation of pea ADH is pH-dependent and is maximal at pH 9.0. NAD protects the enzyme from inactivation by p-chloromercuribenzoate; the higher the concentration of the coenzyme and the longer the period of incubation of NAD with the enzyme, the lower the degree of inactivation. Ethanol does not prevent the enzyme from inactivation. o-Phenanthroline in a concentration of 1 . 10-3 mol l-1 decreases the degree of inactivation of the enzyme by p-chloromercuribenzoate by 20%; imidazole is without effect on the reaction. Zn2+-ions in concentration of 1 . 10-5 mol l-1 also partly protect the enzyme from inactivation by p-chloromercuribenzoate. The results obtained show that the SH-groups sensitive to labeling with p-chloromercuribenzoate are localized in the active center of the enzyme, probably in the coenzyme-binding site. The protective action of Zn2+-ions and of o-phenanthroline against this inactivation confirms the assumption that the SH-group acts as a zinc ligand in the active center of the enzyme.

Role of fat-derived substrates in the regulation of gluconeogenesis during fasting

1996 ◽  
Vol 270 (5) ◽  
pp. E822-E830 ◽  
Author(s):  
F. Fery ◽  
L. Plat ◽  
C. Melot ◽  
E. O. Balasse
Keyword(s):  
Ketone Body ◽  
Ketone Bodies ◽  
Glucose Turnover ◽  
Oxidation Rates ◽  
Relative Contribution ◽  
Beta Hydroxybutyrate ◽  
Hormonal Milieu ◽  
Body Concentration

To determine the role of fat-derived substrates in the regulation of glucose metabolism during fasting, glucose turnover, urea nitrogen production, alanine conversion to glucose, and substrate oxidation rates were measured in 34 normal 4-day-fasted volunteers treated with the antilipolytic drug acipimox or placebo for 8 h. The approximately 50% inhibition of lipolysis induced by acipimox increased glucose concentration and production, respectively, by approximately 35 and approximately 30%, whereas the protein breakdown and the amount of alanine converted to glucose were increased, respectively, by approximately 70 and approximately 85%. Insulin levels were reduced by approximately 40%, cortisol levels doubled, and growth hormone concentration increased sevenfold. The relative contribution of free fatty acid (FFA) and ketone body lowering to the observed response was evaluated in nine acipimox-treated subjects in whom ketone body concentration was clamped with an intravenous beta-hydroxybutyrate infusion. The results of these experiments suggest that, during fasting, both FFA and ketone bodies tend to suppress gluconceogenesis and to protect the protein stores. FFA seem to exert their effects mainly through their ability to modulate the hormonal milieu (especially insulin), whereas ketone bodies seem to act mainly by other mechanisms. Thus the widespread view according to which FFA exert a stimulatory role on gluconeogenesis does not apply to the fasting state in vivo.

scholarly journals The role of leucine in ketogenesis in starved rats

1982 ◽  
Vol 204 (2) ◽  
pp. 399-403 ◽  
Author(s):  
L K Thomas ◽  
M Ittmann ◽  
C Cooper
Keyword(s):  
Intravenous Injection ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Specific Radioactivity ◽  
Body Carbon ◽  
Blood Ketone Bodies

The quantitative significance of the conversion in vivo of L-[U-14C]leucine to ketone bodies was determined in rats starved for 3 or 48 h. In animals starved for 3 h, 4.4% of ketone-body carbon is derived from the metabolism of leucine, and in rats starved for 48 h the corresponding value is 2.3%. This conversion occurs rapidly, and the specific radioactivity of ketone bodies in blood is maximal at 2 min after the intravenous injection of labelled leucine for both periods of starvation. The flux of leucine in the blood is 1.01 and 1.04 mumol/min per 100 g body wt. respectively for animals starved for 3 and 48 h. The specific radioactivity of blood ketone bodies was compared at 2 min after the injection of labelled leucine, lysine and phenylalanine. The specific radioactivity was 4-5 fold higher with leucine than with lysine or phenylalanine.

Role of ketone bodies in perinatal myocardial energy metabolism

2001 ◽  
Vol 29 (2) ◽  
pp. 325-330 ◽  
Author(s):  
B. Bartelds ◽  
F. R. van der Leij ◽  
J. R. G. Kuipers
Keyword(s):  
Oxygen Consumption ◽  
Energy Production ◽  
Ketone Body ◽  
Myocardial Metabolism ◽  
Ketone Bodies ◽  
Left Ventricular ◽  
Energy Utilization ◽  
Long Chain Fatty Acids ◽  
Near Term

Metabolic changes at around the time of birth are crucial for life. Here we review the energy utilization in the myocardium, emphasizing ketone body metabolism. Before birth, glucose and lactate are the major energy substrates for the myocardium. Long-chain fatty acids (LCFA) are normally not available as an energy substrate for the fetal heart; however, when LCFA are supplied artificially in near-term fetal lambs, they are readily oxidized. Hence the myocardium has no limitation to its ability to use LCFA before birth. After birth, lactate remains an important energy source for the myocardium, whereas the contribution of glucose to myocardial energy production decreases despite an increase in the supply of glucose. The oxidation of ketone bodies increases after birth in relation to an increase in supply. However, ketone bodies account for only 7% of left ventricular oxygen consumption. The supply and contribution of LCFA to the myocardium increases after birth; the oxidation of LCFA accounts for most of the left ventricular oxygen consumption. Hence the role of ketone bodies in myocardial metabolism is limited. However, there are interesting observations on interference between the uptake of different substrates and the release of ketone bodies, which might have consequences for our interpretation of ketone body utilization.

scholarly journals Specific binding of 4-hydroxyestradiol to mouse uterine protein: evidence of a physiological role for 4-hydroxyestradiol

2005 ◽  
Vol 185 (2) ◽  
pp. 235-242 ◽  
Author(s):  
C S A Markides ◽  
J G Liehr
Keyword(s):  
Competitive Inhibition ◽  
Specific Binding ◽  
Physiological Role ◽  
Specific Protein ◽  
Selective Binding ◽  
First Order Kinetics ◽  
17Β Estradiol ◽  
The Difference ◽  
Old Mice

There are several indications of a possible physiological role for 4-hydroxyestradiol (4-OHE2) in hormone-responsive tissues. To examine a hormonal activity of 4-OHE2, we have studied the binding of 3H-labeled 4-OHE2 to mouse uterine cytosolic protein. In uteri of 3-week-old mice, total binding was 319.4 ± 13.9 fmol/mg protein. Binding in the presence of excess unlabeled 4-OHE2 dropped to 82.1 ± 1.7 fmol/mg protein, whereas 214.6 ± 9.4 fmol/mg protein bound while incubating in an excess of unlabeled 17β-estradiol (E2). The difference between the two binding values in the presence of excess steroid (132.5 ± 11.1 fmol/mg protein) is taken as selective binding of 4-OHE2 to a specific protein. In mice older than 4 weeks, the specific 4-OHE2 binding declined: 32.0 ± 4.0 fmol/mg protein at 8 weeks, 54.8 ± 6.3 fmol/mg protein at 12 weeks and 54.6 ± 5.2 fmol/mg protein at 9 months. Of other organs tested (liver, kidney, lung and whole brain) only lung showed significant selective binding of 4-OHE2. When E2-binding sites are blocked, binding follows first-order kinetics, yielding a dissociation constant (Kd) value of 11.8 ± 2.1 nM. The specific binding of 4-OHE2 was not inhibited by any other steroids or estrogen metabolites that were tested, except for 2-hydroxyestradiol (2-OHE2), which displayed competitive inhibition of 4-OHE2 binding with an inhibition constant (Ki) value of 98.2 ± 12.6 nM. These results lead us to conclude that 4-OHE2 binds to a specific binding protein, distinct and different from binding to estrogen receptors (ERα and ERβ). The physiological role of this binding remains to be elucidated.

The role of differential phase contrast in electron microscopy

1978 ◽  
Vol 36 (1) ◽  
pp. 176-177
Author(s):  
E.M. Waddell ◽  
J.N. Chapman ◽  
R.P. Ferrier
Keyword(s):  
Phase Contrast ◽  
Practical Method ◽  
Position Vector ◽  
Differential Phase ◽  
Pure Phase ◽  
Differential Phase Contrast ◽  
The Difference ◽  
Image Position ◽  
First Moment

Dekkers and de Lang (1977) have discussed a practical method of realising differential phase contrast in a STEM. The method involves taking the difference signal from two semi-circular detectors placed symmetrically about the optic axis and subtending the same angle (2α) at the specimen as that of the cone of illumination. Such a system, or an obvious generalisation of it, namely a quadrant detector, has the characteristic of responding to the gradient of the phase of the specimen transmittance. In this paper we shall compare the performance of this type of system with that of a first moment detector (Waddell et al.1977).For a first moment detector the response function R(k) is of the form R(k) = ck where c is a constant, k is a position vector in the detector plane and the vector nature of R(k)indicates that two signals are produced. This type of system would produce an image signal given bywhere the specimen transmittance is given by a (r) exp (iϕ (r), r is a position vector in object space, ro the position of the probe, ⊛ represents a convolution integral and it has been assumed that we have a coherent probe, with a complex disturbance of the form b(r-ro) exp (iζ (r-ro)). Thus the image signal for a pure phase object imaged in a STEM using a first moment detector is b2 ⊛ ▽ø. Note that this puts no restrictions on the magnitude of the variation of the phase function, but does assume an infinite detector.

On the Role of Transferrin in 67Ga Uptake by Tumor Cells

1988 ◽  
Vol 27 (04) ◽  
pp. 151-153
Author(s):  
P. Thouvenot ◽  
F. Brunotte ◽  
J. Robert ◽  
L. J. Anghileri
Keyword(s):  
Specific Binding ◽  
Subcellular Fractionation ◽  
Animal Blood ◽  
Tumor Bearing ◽  
Cell Structures ◽  
The Difference ◽  
Sarcoma Cells ◽  
In Vitro Uptake

In vitro uptake of 67Ga-citrate and 59Fe-citrate by DS sarcoma cells in the presence of tumor-bearing animal blood plasma showed a dramatic inhibition of both 67Ga and 59Fe uptakes: about ii/io of 67Ga and 1/5o of the 59Fe are taken up by the cells. Subcellular fractionation appears to indicate no specific binding to cell structures, and the difference of binding seems to be related to the transferrin chelation and transmembrane transport differences

REFLECTION COEFFICIENT OF AN ELECTROMAGNETIC WAVE IN CONDUCTIVE MEDIA

2018 ◽  
pp. 100-106
Author(s):  
M. S. Sudakova ◽  
M. L. Vladov ◽  
M. R. Sadurtdinov
Keyword(s):  
Reflection Coefficient ◽  
Ground Penetrating Radar ◽  
Electromagnetic Waves ◽  
Water Contamination ◽  
Survey Design ◽  
Direct And Inverse Problems ◽  
The Difference ◽  
Ground Penetrating ◽  
Ideal Dielectric

Within the ground penetrating radar bandwidth the medium is considered to be an ideal dielectric, which is not always true. Electromagnetic waves reflection coefficient conductivity dependence showed a significant role of the difference in conductivity in reflection strength. It was confirmed by physical modeling. Conductivity of geological media should be taken into account when solving direct and inverse problems, survey design planning, etc. Ground penetrating radar can be used to solve the problem of mapping of halocline or determine water contamination.

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