scholarly journals The existence of a glyconeogenic pathway in rat skin

1976 ◽  
Vol 156 (2) ◽  
pp. 465-468 ◽  
Author(s):  
R F Peters ◽  
A M White
Keyword(s):  
Pyruvate Carboxylase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Rat Skin ◽  
Fructose 1,6 Bisphosphatase

The existence of a glyconeogenic pathway in rat skin has been demonstrated by measurement of three of the key glyconeogenic enzymes, fructose 1,6-bisphosphatase, pyruvate carboxylase and phosphoenolpyruvate carboxykinase, and by studies on the incorporation in vitro of carbon from pyruvate and alanine into skin glycogen.

scholarly journals [14C]bicarbonate fixation into glucose and other metabolites in the liver of the starved rat under halothane anaesthesia. Metabolic channelling of mitochondrial oxaloacetate

1985 ◽  
Vol 227 (3) ◽  
pp. 851-865 ◽  
Author(s):  
D F Heath ◽  
J G Rose
Keyword(s):  
Pyruvate Carboxylase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Co2 Exchange ◽  
Published Data ◽  
Citrate Cycle ◽  
Incomplete Mixing ◽  
Metabolic Channelling ◽  
Glucose Output

Previous attempts to account for the labelling in vivo of liver metabolites associated with the citrate cycle and gluconeogenesis have foundered because proper allowance was not made for the heterogeneity of the liver. In the basal state (anaesthetized after 24h starvation) this heterogeneity is minimal, and we show that labelling by [14C]bicarbonate can be interpreted unambiguously. [14C]Bicarbonate was infused to an isotopic steady state, and measurements were made of specific radioactivities of blood bicarbonate, alanine, glycerol and lactate, of liver alanine and lactate, and of individual carbon atoms in blood glucose and liver aspartate, citrate and malate. (Existing methods for several of these measurements were extensively modified.) The results were combined with published rates of gluconeogenesis, uptake of gluconeogenic precursors by the liver, and citrate-cycle flux, all measured under similar conditions, and with estimates of other rates made from published data. To interpret the results, three ancillary measurements were made: the rate of CO2 exchange by phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32) under conditions that simulated those in vivo; the 14C isotope effect in the pyruvate carboxylase (EC 6.4.1.1) reaction (14C/12C = 0.992 +/- 0.008; S.E.M., n = 8); the ratio of labelling by [2-14C]- to that by [1-14C]-pyruvate of liver glutamate 1.5 min after injection. This ratio, 3.38, is a measure of the disequilibrium in the mitochondria between malate and oxaloacetate. The data were analysed with due regard to experimental variance, uncertainties in values of fluxes measured in vitro, hepatic heterogeneity and renal glucose output. The following conclusions were reached. The results could not be explained if CO2 fixation was confined to pyruvate carboxylase and there was only one, well-mixed, pool of oxaloacetate in the mitochondria. Addition of the other carboxylation reactions, those of PEPCK, isocitrate dehydrogenase (EC 1.1.1.42) and malic enzyme (EC 1.1.1.40), was not enough. Incomplete mixing of mitochondrial oxaloacetate had to be assumed, i.e. that there was metabolic channelling of oxaloacetate formed from pyruvate towards gluconeogenesis. There was some evidence that malate exchange across the mitochondrial membrane might also be channelled, with incomplete mixing with that in the citrate cycle. Calculated rates of exchange of CO2 by PEPCK were in agreement with those measured in vitro, with little or no activation by Fe2+ ions.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Metabolic control of hepatic gluconeogenesis during exercise

1983 ◽  
Vol 212 (3) ◽  
pp. 633-639 ◽  
Author(s):  
G L Dohm ◽  
E A Newsholme
Keyword(s):  
Metabolic Control ◽  
Pyruvate Kinase ◽  
Pyruvate Carboxylase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Prolonged Exercise ◽  
Allosteric Effectors ◽  
Fructose 1,6 Bisphosphatase ◽  
Metabolite Concentrations ◽  
Fructose 1,6 Bisphosphate ◽  
Hexose Phosphates

Prolonged exercise increased the concentrations of the hexose phosphates and phosphoenolpyruvate and depressed those of fructose 1,6-bisphosphate, triose phosphates and pyruvate in the liver of the rat. Since exercise increases gluconeogenic flux, these changes in metabolite concentrations suggest that metabolic control is exerted, at least, at the fructose 6-phosphate/fructose 1,6-bisphosphate and phosphoenolpyruvate/pyruvate substrate cycles. Exercise increased the maximal activities of glucose 6-phosphatase, fructose 1,6-bisphosphatase, pyruvate kinase and pyruvate carboxylase in the liver, but there were no changes in those of glucokinase, 6-phosphofructokinase and phosphoenolpyruvate carboxykinase. Exercise changed the concentrations of several allosteric effectors of the glycolytic or gluconeogenic enzymes in liver; the concentrations of acetyl-CoA, ADP and AMP were increased, whereas those of ATP, fructose 1,6-bisphosphate and fructose 2,6-bisphosphate were decreased. The effect of exercise on the phosphorylation-dephosphorylation state of pyruvate kinase was investigated by measuring the activities under conditions of saturating and subsaturating concentrations of substrate. The submaximal activity of pyruvate kinase (0.5 mM-phosphoenolpyruvate), expressed as percentage of Vmax., decreased in the exercised animals to less than half that found in the controls. These changes suggest that hepatic pyruvate kinase is less active during exercise, possibly owing to phosphorylation of the enzyme, and this may play a role in increasing the rate of gluconeogenesis.

scholarly journals The Yeast GID Complex, a Novel Ubiquitin Ligase (E3) Involved in the Regulation of Carbohydrate Metabolism

2008 ◽  
Vol 19 (8) ◽  
pp. 3323-3333 ◽  
Author(s):  
Olivier Santt ◽  
Thorsten Pfirrmann ◽  
Bernhard Braun ◽  
Jeannette Juretschke ◽  
Philipp Kimmig ◽  
...  
Keyword(s):  
Carbohydrate Metabolism ◽  
Ubiquitin Ligase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Ring Finger ◽  
Vitro Assay ◽  
Fructose 1,6 Bisphosphatase ◽  
Key Enzyme ◽  
Ubiquitin Ligase E3

Glucose-dependent regulation of carbon metabolism is a subject of intensive studies. We have previously shown that the switch from gluconeogenesis to glycolysis is associated with ubiquitin-proteasome linked elimination of the key enzyme fructose-1,6-bisphosphatase. Seven glucose induced degradation deficient (Gid)-proteins found previously in a genomic screen were shown to form a complex that binds FBPase. One of the subunits, Gid2/Rmd5, contains a degenerated RING finger domain. In an in vitro assay, heterologous expression of GST-Gid2 leads to polyubiquitination of proteins. In addition, we show that a mutation in the degenerated RING domain of Gid2/Rmd5 abolishes fructose-1,6-bisphosphatase polyubiquitination and elimination in vivo. Six Gid proteins are present in gluconeogenic cells. A seventh protein, Gid4/Vid24, occurs upon glucose addition to gluconeogenic cells and is afterwards eliminated. Forcing abnormal expression of Gid4/Vid24 in gluconeogenic cells leads to fructose-1,6-bisphosphatase degradation. This suggests that Gid4/Vid24 initiates fructose-1,6-bisphosphatase polyubiquitination by the Gid complex and its subsequent elimination by the proteasome. We also show that an additional gluconeogenic enzyme, phosphoenolpyruvate carboxykinase, is subject to Gid complex-dependent degradation. Our study uncovers a new type of ubiquitin ligase complex composed of novel subunits involved in carbohydrate metabolism and identifies Gid4/Vid24 as a major regulator of this E3.

scholarly journals Gluconeogenesis in the amphibian retina. Lactate is preferred to glutamate as the gluconeogenic precursor

1988 ◽  
Vol 254 (2) ◽  
pp. 359-365 ◽  
Author(s):  
S S Goldman
Keyword(s):  
Energy Metabolism ◽  
Cyclic Amp ◽  
Pyruvate Carboxylase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Lactate Production ◽  
Glycogen Metabolism ◽  
Hepatic Tissue ◽  
Ionophore A23187 ◽  
Fructose 1,6 Bisphosphatase ◽  
Full Complement

The capacity for gluconeogenesis in the isolated amphibian retina was found to be approx. 70-fold greater with lactate than with glutamate as the gluconeogenic precursor, 1426 versus 21 pmol of glucose incorporated into glycogen/h per mg of protein. It was also found that 11-15% of the glucosyl units in glycogen are derived from C3 metabolites of the glycolytic pathway, suggesting that lactate is recycled within the retina. In concert with these metabolic observations, a full complement of the gluconeogenic enzymes was detected in retinal homogenates. These included: glucose-6-phosphatase, fructose-1,6-bisphosphatase, acetyl-CoA-dependent pyruvate carboxylase and phosphoenolpyruvate carboxykinase. Agents that regulate the rate of gluconeogenesis in hepatic tissue were tested on the retina. At concentrations of glutamate and lactate that are presumed to be relevant physiologically, it was found that vasoactive intestinal peptide, ionophore A23187 and elevated [K+] each enhanced the rate of gluconeogenesis in Ringer containing 50 microM-glutamate, whereas in Ringer containing 8.5 mM-lactate these agents inhibited the rate of gluconeogenesis. Further, it was found that the classic gluconeogenic hormone glucagon inhibited gluconeogenesis in both glutamate- and lactate-containing Ringer. Retinal energy metabolism was found to be altered in lactate-containing Ringer, in that lactate production was suppressed completely. In addition, glycogen metabolism appeared to be dependent on increased cytosolic Ca2+ and was insensitive to increased retinal cyclic AMP.

Effect of Endurance Training and Fasting on Renal Gluconeogenic Enzymes in the Rat

2004 ◽  
Vol 14 (3) ◽  
pp. 323-332 ◽  
Author(s):  
Ken D. Sumida ◽  
Jeff H. Garrett ◽  
William T. Mcjilton ◽  
Andrea L. Hevener ◽  
Casey M. Donovan
Keyword(s):  
Enzyme Activities ◽  
Pyruvate Carboxylase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Training Status ◽  
Chronic Exercise ◽  
Fed State ◽  
Fasted State ◽  
Significant Difference ◽  
Fructose 1,6 Bisphosphatase ◽  
Gluconeogenic Enzyme

The purpose of this study was to examine the effects of chronic exercise training (running 30 m/min, 10% grade, 90 min/d for 8–10 weeks) on specific renal enzyme activities involved with the gluconeogenic pathway in the fed and 24-hr fasted state in rats. A portion of the kidney (containing the cortex and medulla) was homogenized from which cytosolic (c) and mitochondrial (m) fractions were separated. Maximal gluconeogenic enzyme activities were assessed for: phosphoenolpyruvate carboxykinase (cPEPCK), fructose 1,6-bisphosphatase (cFBP), pyruvate carboxylase (mPC), aspartate aminotrans-ferase (cAspAT), alanine aminotransferase (cAlaAT), and lactate dehydroge-nase (cLDH). In the fed state, there was no significant difference between groups in any of the enzymes examined (nmoles/min × mg protei n–1): cPEPCK (25.8 ± 1.7), cFBP(106.8 ± 7.1), mPC (20.7 ± 1.8), cAspAT( 1047.1 ±38.6), cAlaAT (52.3 ±4.3), and cLDH(1728.6± 163.2). After the 24-hr fast, there was a significant increase in cPEPCK (52.4 ± 2.9 and 52.0 ± 2.1) and mPC (44.6 ± 4.3 and 47.6 ± 4.9), control and trained, respectively. These results suggest that the maximal enzyme activities for cPEPCK and mPC can be augmented as a result of fasting that was independent of the training status.

A putative pathway of glyconeogenesis in skeletal muscle

1981 ◽  
Vol 1 (2) ◽  
pp. 157-165 ◽  
Author(s):  
Bhanu R. Odedra ◽  
T. Norman Palmer
Keyword(s):  
Skeletal Muscle ◽  
Malic Enzyme ◽  
Pyruvate Carboxylase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
De Novo ◽  
Glycogen Biosynthesis ◽  
Glycogen Sparing ◽  
Specific Inhibitors

Evidence is presented in support of a pathway in skeletal muscle of glyconeogenesis (glycogen biosynthesis de novo) from L-glutamate and related amino acids involving the enzyme phosphoenolpyruvate carboxykinase (PEP CK). In the rat hemidiaphragm in vitro, not only did L-[U-14C]glutamate exert a glycogen-sparing action, but14C-label was incorporated into glycogen. The incorporation is thought not to be simply via label randomization and was decreased by factors that increased glycolysis or pyruvate oxidation. 3-Mercaptopicolinate and amino-oxyacetate, specific inhibitors of PEP CK and aminotransferase-type enzymes, respectively, decreased14C-incorporation from L-[U-14C]glutamate into glycogen. No quantitative determination of apparent glyconeogenic flux was made, and it remains to be established whether glyconeogenesis via PEP CK and/or via PEP CK coupled with 'malic' enzyme (or pyruvate carboxylase) is functionally important in skeletal muscle.

Formulation and Evaluation of Carbopol Gel Containing Liposomes of Ketoconazole. (Part-II)

2009 ◽  
Vol 1 (2) ◽  
Author(s):  
Rakesh Patel ◽  
Hardik Patel ◽  
Ashok Baria
Keyword(s):  
Antifungal Activity ◽  
Rat Skin ◽  
Albino Rat ◽  
In Vitro Drug Release ◽  
Carbopol Gel ◽  
Liposomal Formulations ◽  
Release Drug ◽  
In Vitro Permeation ◽  
In Vitro Antifungal Activity

The aim of this work was to prepare and evaluate the topical carbopol gel formulation containing ketoconazole encapsulated liposomes. Ketoconazole loaded liposomes were prepared by thin film hydration technique. The prepared liposomes were incorporated into 1% carbopol gel, and the systems were evaluated for in-vitro drug release, drug retention into skin and in-vitro antifungal activity. The in-vitro permeation of ketoconazole using wistar albino rat skin from liposomal gel was compared with that of plain drug gel and also with plain drug cream containing 2% w/w of ketoconazole. The release of ketoconazole from liposomal gel was much slower than from non liposomal formulations. Gel containing liposomal ketoconazole showed maximum antifungal activity after 30 hours over plain ketoconazole gel and cream formulations.

The effect of glycerin as penetration enhancer in a ketoprofen solid preparation–patch on in vitro penetration study through rat skin

2020 ◽  
Vol 23 (03) ◽  
pp. 71-83
Author(s):  
Pratama Ferina Nadya ◽  
Umam Choirul ◽  
Ameliana Lidya ◽  
Nurahmanto Dwi
Keyword(s):  
Penetration Enhancer ◽  
Rat Skin
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