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Query: UNIPROT:P06889 (Mol)
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The in vitro metabolism of [1-13C]glucose by Ascaris suum third and fourth-stage larvae was analyzed under different gas phases using 13C nuclear magnetic resonance spectroscopy (13C-NMR). Third-stage larvae (L3) incubated under a gas phase of 85% N2/5% O2/10% CO2 produced trace amounts of [13C]succinate, and molted to fourth-stage larvae (L4) between days 3 and 4 in vitro. However, they appeared to arrest as L3s when incubated under air, or 85% N2/5% O2/10% CO2 in the presence of 2 mM potassium cyanide, or 95% N2/5% CO2. Day 12 L4 (eight days after molting) incubated under 85% N2/5% O2/10% CO2, or 95% N2/5% CO2, or 94% N2/1% O2/5% CO2, produced succinate, acetate, propionate and the branched-chain fatty acids 2-methylvalerate and 2-methylbutyrate by fermentative pathways characteristic of adult body wall muscle. In contrast, when Day 12 L4 were incubated under air, only trace amounts of these acids were detected in the incubation medium. Thus, L4 are capable of synthesizing end-products typical of the adult even in the presence of oxygen, as long as the CO2 tensions are above 5%. As would be predicted, activities of enzymes involved in aerobic metabolism, including citrate synthase, isocitrate dehydrogenase, and cytochrome oxidase, decreased dramatically as L4s underwent the final ecdysis and matured to the adult stage. More importantly, activities of enzymes typical of anaerobic metabolism, including phosphoenolpyruvate carboxykinase and malic enzyme, were substantially elevated in L3s (over their levels in second-stage larvae), and appeared to have reached their adult levels in L3s prior to the third molt, even though L3s still exhibited cyanide sensitivity. Since L3s and L4s have enzymes involved in both aerobic and anaerobic pathways, it is possible that the L3s contain two populations of mitochondria, one which functions aerobically and a second which functions anaerobically.
Mol Biochem Parasitol 1989 Aug
PMID:Effect of gas phase on carbohydrate metabolism in Ascaris suum larvae. 250 8

The effects of ischemia, reperfusion and hypoxia on the cardiac acetylcholine, choline, norepinephrine and cyclic AMP contents were investigated in isolated, spontaneously beating rat hearts perfused under constant pressure (100 cm H2O) with Krebs-Henseleit solution gassed with 95% O2-5% CO2. Acetylcholine, choline and norepinephrine were determined by high performance liquid chromatography with electrochemical detection. Cyclic AMP was determined by radioimmunoassay. One min reperfusion following 15 min ischemia (termination of perfusion) caused a significant decrease in both cardiac acetylcholine (P less than 0.05) and norepinephrine (P less than 0.01) contents, but had no significant effect on the cardiac norepinephrine/acetylcholine content ratio, or choline or cyclic AMP content. By contrast, 16 min ischemia did not significantly affect the cardiac acetylcholine, norepinephrine, choline or cyclic AMP content. Also, 16 min hypoxia (perfusion with Krebs Henseleit solution gassed with 95% N2 5% CO2) decreased the cardiac norepinephrine content significantly (P less than 0.01) and norepinephrine/acetylcholine content ratio slightly but not significantly. However, hypoxia had no significant effect on the cardiac acetylcholine, choline or cyclic AMP content. Pre-treatment with 10 microns atropine sulfate prevented the decrease in the cardiac acetylcholine content caused by reperfusion but caused a significant depletion in the cardiac norepinephrine content in the control (P less than 0.01) and ischemia (P less than 0.05) groups and a significant decrease in the norepinephrine/acetylcholine content ratio in all three groups (all, P less than 0.05). Extending the reperfusion period to 5 and 10 min following 15 min ischemia also caused a significant decrease in both cardiac acetylcholine and norepinephrine contents compared with the control groups. However, no significant difference in these contents was found between 1 min reperfusion group and 5 or 10 min reperfusion group. Twenty or 25 min ischemia alone did not significantly affect these contents. These findings suggest that reperfusion disturbs both the sympathetic and parasympathetic nervous systems in the heart and that pre-treatment with atropine adversely affects the balance of the autonomic nervous system.
J Mol Cell Cardiol 1989 Feb
PMID:Effect of reperfusion on the cardiac acetylcholine and norepinephrine contents in rat hearts. 254 84

Incubation of the isolated mouse diaphragm with a high rate of oxygenation (10 ml s-1, 95% O2 + 5% CO2) causes a characteristic cellular damage with widely-separated myofibrils and swollen sarcotubular system within 10 min. This damage was ameliorated by inhibitors of the hydroxyl radical (.OH), desferrioxamine, dimethyl thiourea and 120 mM mannitol, and by incubation at 8 degrees C. It was not prevented either by inhibitors of the pathway leading to sarcolemma damage (nordihydroguaiaretic acid, alpha-tocopherol, butylated hydroxytoluene) nor by agents and treatments that inhibit the oxygen paradox of cardiac muscle (glucose, omission of extracellular calcium, incubation at 30 degrees C, superoxide dismutase and catalase). Nevertheless there are similarities between these two types of damage triggered by O2 and the possibility that in both an NAD(P)H oxidase is stimulated and cytotoxic oxygen radicals are generated is discussed.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Cytotoxic effect of oxygen on the skeletal muscle of mouse diaphragm. 256 50

The focus of this review centered on describing the effects of excess fatty acids on myocardial recovery during reperfusion following ischemic stress. Effects on mechanical function were modest in our studies and are likely to remain difficult/impossible to measure due to the independent phenomenon of stunning which obfuscates and no doubt dominates the influences of other mechanical determinants. Mitochondria appear capable of again using long-chain fatty acids as a preferred substrate and in the presence of restored oxygen delivery can produce normal levels of CO2. These changes in oxidative metabolism are not mirrored by equal recoveries in mitochondrial energetics. Because of inefficiencies in electron transport and oxidative phosphorylation together with moderate uncoupling of electron transport from oxidative phosphorylation, ATP resynthesis is blunted. This explains in part the absolute decrease in contents of exchangeable nucleotides noted both in cytosol and mitochondria. Further impairments in recovery reside in the inability of the mitochondria to exchange adenine nucleotides into cytosol through the adenine nucleotide translocase antiport. These findings contribute to our understanding of mechanical stunning and may be of value in designing future strategies to optimize the handling of substrates during myocardial reperfusion.
Mol Cell Biochem
PMID:Alterations in fatty acid oxidation in ischemic and reperfused myocardium. 267 64

We have determined the complete nucleotide sequence of a full length cDNA encoding the Crassulacean acid metabolism (CAM) isogene of phospho(enol)pyruvate carboxylase (PEPCase). The cDNA clone, 3348 bp in length, was obtained from mRNA isolated from Mesembryanthemum crystallinum (common ice plant) which had undergone salt stress and subsequent induction of CAM. The long open reading frame encodes PEPCase (EC 4.1.1.31) with a predicted molecular mass of 110533 daltons. The deduced amino acid sequence of the ice plant PEPCase is most similar to that from maize having an amino acid identity of 74.9%. Sequence identity in corresponding regions of the PEPCase proteins from Escherichia coli and the cyanobacterium Anacystis nidulans are 41.4% and 33.5%, respectively. A compilation of the four amino acid sequences permitted the identification of phylogenetically conserved regions within the proteins which may play a role in the function of this important enzyme in plant metabolism. Gene specific probes from 3' coding and noncoding regions of the cDNA clone used to probe genomic Southern blots established that this PEPCase gene is present in one copy in the nuclear genome of M. crystallinum. Transcripts arising from this gene increase dramatically when M. crystallinum is irrigated with 0.5 M NaCl, a stress which induces this plant to switch the primary fixation of CO2 from C3 (Calvin cycle) to CAM mode. The salt-induced mRNA encodes a PEPCase isoform which is undetectable in plants in the C3 mode as demonstrated by Northern hybridization.
Mol Gen Genet 1989 Feb
PMID:Expression of the CAM-form of phospho(enol)pyruvate carboxylase and nucleotide sequence of a full length cDNA from Mesembryanthemum crystallinum. 271 Jan 7

RuBisCO (D-ribulose-1,5-biphosphate carboxylase/oxygenase; EC 4.1.1.39) has been isolated from the autotrophic hydrogen-oxidizing bacterium Alcaligenes eutrophus H16. Combining photon correlation and sedimentation analysis transport parameters of the enzyme were investigated in the active, (E.CO2.Mg2+) as a ternary complex, and inactive state, (E.CO2.Mg2+.CABP) as a quaternary complex, where RuBisCO is complexed with the transition state analogue CABP (2-C-carboxy-D-arabinitol-1,5-biphosphate). Within experimental error, no difference has been detected between the diffusion and sedimentation coefficients (D020,w = 2.72(+/- 0.07) x 10(-7) cm2 s-1, s020,w = 17.8(+/- 0.5)S) of active and CABP-complexed enzyme thus leading to the conclusion that the molecule, at least in solution, does not assume a different conformation when complexed with CABP.
J Mol Biol 1989 Jun 05
PMID:Comparative studies of ribulose-1,5-biphosphate carboxylase/oxygenase from Alcaligenes eutrophus H16 cells, in the active and CABP-inhibited forms. 276 Sep 25

The effect of hypoxia on myocardial lipolysis (glycerol release) was investigated in freshly isolated, calcium-tolerant rat ventricular myocytes. Hypoxia was produced by gassing the incubation medium (Joklik-minimum essential medium, supplemented with 1.2 mM MgSO4, 1 mM DL-carnitine, 1.5 mM CaCl2 and 0.6 mM palmitate bound to 0.15 mM fatty acid free bovine serum albumin) with 95% N2-5% CO2. Control (normoxic) incubations were carried out under air-5% CO2 atmosphere. Basal glycerol release increased from 46.6 +/- 3.0 nmol/10(6) cells.30 min in normoxia to 64.5 +/- 4.3 nmol/10(6) cells.30 min in hypoxia (p less than 0.05). Addition of isoprenaline (10 microM) resulted in a significant (p less than 0.05) stimulation of the glycerol release both in normoxia and in hypoxia, but the enhancement above basal rates was apparently lower in hypoxia (8.7 +/- 2.5 nmol/10(6) cells.30 min) than in normoxia (12.2 +/- 2.7 nmol/10(6) cells.30 min). Furthermore, whereas the isoprenaline-induced rise in lipolysis both in normoxia and hypoxia was prevented by inclusion of propranolol (10 microM), propranolol did not affect the hypoxia-induced increase in lipolysis. Thus, the above findings suggest that myocardial lipolysis may be stimulated by local non-adrenergic mechanisms during hypoxia.
Mol Cell Biochem
PMID:Effects of hypoxia on lipolysis in isolated rat myocardial cells. 277 33

Iodinated fatty acids (FAs) are now used in Nuclear Medicine to assess, by external detection, myocardial metabolism. Methylated FAs have been proposed as tracers of FA myocardial uptake. IMPPA is a new FA analogue in which a methyl group have been introduced in beta position to inhibit beta-oxidation and a terminal phenyl group prevents a possible omega oxidation. We have compared the intramyocardial behaviour of this FA with the 15-p-iodophenyl-pentadecanoic acid (IPPA), the straight chain analogue, and with the 15-phenyl-beta-methylpentadecanoic acid (MPPA), the 3 of them being labelled with C14 on the carboxyl group, in isolated rat hearts perfused in a recirculating system. When IMPPA is compared to IPPA (influence of the methyl group), we observe 1--an inhibition of beta-oxidation (no significant production of labelled CO2 and very low radioactivity in the aqueous phase) leading to a reduced uptake, 2--a lower radioactivity in the organic phase due to a hindrance to the esterification process both into TGs and PLs, the free FAs level being higher. When IMPPA is compared to MPPA (influence of the iodine atom), we observe 1--the same inhibition of beta-oxidation, 2 - a higher myocardial radioactivity due to a much higher level of free FAs, the esterification into TGs and PLs being reduced. This study with IMPPA indicates that it is taken up by the heart and trapped there, as it is not oxydized. This long retention time, apart from giving good scintigraphic images, should make IMPPA useful to study the regional myocardial uptake of FAs.
Mol Cell Biochem
PMID:Intramyocardial fate of 15-p-iodophenyl-beta-methylpentadecanoic acid (IMPPA): is it a good tracer of fatty acid myocardial uptake? 277 41

The metabolism by coronary microvascular endothelial cells (CMEC) of the heart typical substrates palmitate and lactate was compared to that of glucose and glutamine. Confluent cultures of CMEC were used. Palmitate oxidation was saturable and independent of the exogenous albumin concentration. Palmitate, 300 microM, lactate, 1 mM, and glutamine, 0.5 mM, were oxidized to 35, 46, and 56 nmol CO2/h x mg protein. These oxidation rates were decreased by 80, 66, and 48% in presence of 5 mM glucose. The largest energy yield was obtained by glycolytic breakdown of glucose. Glucose, 5 mM, was degraded to lactate by 99%, and oxidized in the Krebs cycle by only 0.04%. 1% was catabolized via the hexose monophosphate pathway. The rate of glucose oxidation in the Krebs cycle could be 30-fold increased by the uncoupler 2,4-dinitrophenol, 30 microM. At concentrations lower than 1 mM the amount of glucose oxidized in the Krebs cycle also grew, indicating existence of the Crabtree effect. The energy demand of CMEC seems to be of the same order as that of the arrested heart.
Mol Cell Biochem
PMID:Fatty acids are not an important fuel for coronary microvascular endothelial cells. 277 44

The effect of lonidamine (LND), 1-(2,4-dichlorobenzyl)-1H-indazol-3 carboxylic acid, on the utilization of carbon from 14C-labeled glucose by cell cultures of the permanent strain LI derived from a human glioblastoma multiforme (astrocytoma) has been investigated. The results may be summarized as follows. Aerobic glycolysis is the main energy-yielding process as shown by the fact that the greatest part of glucose carbon atoms is incorporated into lactate. Nevertheless, the amount of glucose converted accounts for only 63% of the lactate produced, indicating the presence of an elevated endogenous aerobic glycolysis. The amount of glucose carbon atoms incorporated into CO2, lipids, nucleic acid, and supporting structures is low. LND decreased the incorporation of 14C activity in all the above mentioned isolated compounds because of its ability to inhibit glucose phosphorylation. Consequently, there is a lower concentration of glucose-6-phosphate which, in turn, affects the rate of formation of several metabolites in glycolytic and pentose phosphate pathways. Experiments with [1-14C]-2-deoxy-D-glucose further substantiate the idea of glucose phosphorylation as a main target of LND and strongly suggest the presence of a mitochondrially bound hexokinase. The higher inhibition of glucose phosphorylation in exponentially growing cells indicates a further shift of the enzyme toward mitochondria-bound form and confirms the importance of the energy status of the cell in eliciting the response to LND. The reduced capacity of LND-treated cells to synthetize ATP and glucose-6-phosphate reflects the decreased synthesis of proteins and nucleic acids, which affects cell growth and duplication.
Exp Mol Pathol 1987 Oct
PMID:Effect of lonidamine on the utilization of 14C-labeled glucose by human astrocytoma cells. 282 Jul 86


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