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Query: UNIPROT:P06889 (Mol)
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Labeled iodinated fatty acids (FAs) have been proposed to explore myocardial metabolism by external detection in man. We have chosen a 16-carbon FA, iodinated in omega position, whereas other authors use an iodophenylated FA. To explore the influence of the presence of an iodine or of an iodophenyl radical on the metabolism of the FA, we have compared, in isolated rat hearts perfused in a recirculating system, the intramyocardial fate of palmitate (PA), iodopalmitate (IPA), and iodophenylpentadecanoate (IPPA), the 3 of them being labeled with C14 in position 1. The addition of the iodine atom brings about a hindrance to the esterification of the FA into triglycerides, but not modification of the myocardial uptake and of the CO2 produced. The addition of the iodophenyl radical impairs both the FA storage and its oxidation, leading to a very high level of free FA. The phospholipid distribution is also modified. Apart from their myocardial use in the isolated rat heart, the 3 FAs were assayed in vitro as a substrate for acylCoA-synthase. As IPA more closely mimics native FA metabolism, it is therefore more suitable than IPPA as a tracer of myocardial metabolism.
J Mol Cell Cardiol 1990 Dec
PMID:The intramyocardial fate of [1-14C] palmitate, iodopalmitate and iodophenylpentadecanoate in isolated rat hearts. A contribution to the choice of an iodinated fatty acid as a tracer of myocardial metabolism. 208 56

The ability of coronary endothelial cells in 14 day confluent cultures to metabolize glucose, palmitate, lactate and various amino acids was investigated. Under aerobic conditions, 99% of glucose, (5 mM) was degraded to lactate and only 0.04% was oxidized in the Krebs cycle. One percent of the glucose catabolized was directed into the hexose monophosphate pathway, but this fraction could be increased by 81% by 0.4 mM methylene blue. Glucose oxidation in the Krebs cycle was increased at glucose concentrations lower than 1 mM, or by the uncoupler 2,4-dinitrophenol. Oxidation to CO2 of palmitate (300 microM), lactate (1 mM), and glutamine (0.5 mM) was diminished in the presence of glucose (5 mM) by 80, 66, and 48%, respectively. These results demonstrate that coronary endothelial cells utilize exogenous glucose, at physiological concentration, predominantly for glycolytic energy production. The metabolic pattern is characteristic of the Crabtree effect. In these cells, glucose not only effectively suppresses the oxidation of the substrates lactate and palmitate, i.e. of substrates preferred by the whole heart, but also of glutamine, which is a major oxidative substrate for coronary endothelial cells. Absolute rates of substrate catabolism are low as compared to those of the beating heart indicating a low energy demand of coronary endothelial cells.
J Mol Cell Cardiol 1990 Dec
PMID:Metabolism of exogenous substrates by coronary endothelial cells in culture. 208 57

We propose a quantitative model of the thermodynamics of hemoglobin in contact with its five major ligands (O2, CO2, Cl-, 2,3-bisphosphoglycerate, and H+). Our model incorporates the two-state formalism of J. Monod, J. Wyman, and J.P. Changeux (J. Mol. Biol. 12: 88-118, 1965) for treatment of quanternary transitions and also the mean field formalism of K. Linderstrom-Lang (C. R. Trav. Lab. Carlsberg Ser. Chim. 15: 1-30, 1924) for treatment of electrostatic interactions. On the basis of this approach, we develop an algorithm for the efficient computation of observable quantities, such as the occupancy of various ligand binding sites, and an objective statistical procedure for determining both maximum likelihood values and confidence limits of all the intrinsic thermodynamic parameters of hemoglobin. Finally, we show that the predictions of our theory are in good agreement with independent experimental observations.
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PMID:A thermodynamic model of hemoglobin suitable for physiological applications. 210 52

Leishmania major promastigotes grown in late log phase were incubated with glucose as sole exogenous carbon source in the presence of 5% CO2 and the amounts of glucose consumed and of the major products formed--succinate, pyruvate, alanine, acetate, glycerol, and D-lactate--were measured as a function of pO2. Glucose consumption increased as pO2 was lowered to 6% (a positive Pasteur effect) and then declined to the same level at 95% N2 as at 95% O2. The production of D-lactate and of glycerol increased as pO2 dropped from 95%, reaching a maximum at about 2% O2. Succinate production, however, increased dramatically when pO2 was reduced to 6% and remained at that level with further reduction of pO2. The amount of succinate produced relative to the amount of glucose carbon consumed suggests utilization of an endogenous carbon source. Acetate production did not change between 95% O2 and 6% O2 and then declined with decreasing pO2. These observations suggest the presence of two sensors, one with a high and one with a low affinity for oxygen. When glycerol or alanine were the only exogenous sources of carbon, the primary products released were acetate and succinate. Acetate production from alanine declined slightly as pO2 was reduced to 2%, and then dropped markedly when pO2 was reduced to 0%. Acetate production from glycerol increased over 4-fold when the pO2 was reduced from 95% to 4%, and then declined with further reduction in pO2. No succinate was formed from either substrate until complete anaerobiosis. This pattern of response, while differing from that when glucose was sole exogenous carbon source, is also consistent with the regulation of metabolism by a high and a low affinity O2 sensor. Cells from cultures in early stationary phase, before the appearance of metacyclic forms, consumed glucose at about the same rate as log phase promastigotes, but did not show a Pasteur effect. Stationary cells also consumed glycerol at the same rate as did log phase promastigotes, but consumed alanine at a much lower rate. Reduction of pO2 affected product formation from each of these substrates differently than for log phase promastigotes, demonstrating the sensitivity of several pathways of intermediary metabolism to regulation by pO2 during the transition from log to stationary phase.
Mol Biochem Parasitol 1990 Mar
PMID:Effects of oxygen concentration on the intermediary metabolism of Leishmania major promastigotes. 210 30

The filarial parasite Litomosoides carinii was able to survive for longer than 15 h in basic filarial medium (BFM) containing either glutamine or alanine as a sole substrate. The filariids were more motile in BFM containing glucose, but even higher motility was recorded in media containing both glucose and glutamine. Incubations under aerobic conditions showed that radiolabelled glutamine was metabolised primarily to CO2. In addition, small amounts of lactate and acetate were excreted in almost equimolar quantities. Incubations where both glutamine and glucose were present demonstrated that the glutamine carbon utilised by the parasite could be completely recovered in the above three end products. The glutamine nitrogen could be recovered in the additional excretory products, alanine and ammonia. The glutamine-dependent viability of L. carinii was affected by known inhibitors of the mitochondrial respiratory chain. Glucose utilisation, and the production of CO2 from this substrate, were greatly stimulated by the presence of glutamine in the external medium. Various carbon balance studies, in conjunction with enzymatic analyses, suggest that in L. carinii, glutamine provides an input of carbon into the tricarboxylic acid (TCA) cycle, probably at the level of alpha-ketoglutarate. This increased availability of Krebs cycle intermediates will stimulate the rate of pyruvate oxidation via acetyl-CoA and the TCA cycle, and thus increase the rate of carbon flux through glycolysis. The energetic advantage associated with the utilisation of the glucose/glutamine substrate couple may explain the worm's enhanced motor activity compared to incubations with glucose as the sole energy source. Alanine was found to be degraded by the filariid to equivalent amounts of lactate, acetate and CO2, indicating a relatively low energetic efficiency. There was no detectable uptake of glutamate. A variety of other amino acids tested were neither metabolised nor able to maintain worm viability in vitro.
Mol Biochem Parasitol 1990 Jun
PMID:The role of amino acids in the energy generating pathways of Litomosoides carinii. 211 54

The effects of O2 and CO2 on the growth in culture of Trichomonas vaginalis strain C1-NIH were investigated. Growth under pre-purified N2 in the absence of CO2 supplementation gave a doubling time of 4.4 h; when traces of O2 (less than 0.25 microM) were present, the doubling time was 3.5 h. Organisms grew most rapidly (doubling time 2.3 h) with traces of O2 (less than 0.25 microM) and with the CO2 level controlled at 5 mM. The balance of fermentation products from maltose was greatly influenced by supplied gases. Under strictly anaerobic conditions at 5 mM CO2, equimolar glycerol and lactate accounted for more than 95% of the measured products, whereas lower CO2 increased acetate production. Under microaerobic conditions (O2 less than 0.25 microM) acetate was the major product when CO2 was limited to that evolved endogenously; again 5 mM CO2 favoured glycerol and lactate production. Activities of key enzymes measured in cell-free extracts (pyruvate:ferredoxin oxidoreductase, hydrogenase, glycerol kinase, malate dehydrogenase (decarboxylating) and lactate dehydrogenase) altered with growth conditions commensurately with observed changes in metabolic flux patterns. These results suggest that T. vaginalis is optimally adapted to conditions it experiences in situ in the vagina (traces of O2, high CO2).
Mol Biochem Parasitol 1990 Jun
PMID:Trichomonas vaginalis requires traces of oxygen and high concentrations of carbon dioxide for optimal growth. 211 56

The X-ray structure of the quaternary complex of ribulose 1,5-bisphosphate carboxylase/oxygenase from spinach with CO2, Mg2+ and a reaction-intermediate analogue (CABP) has been determined and refined at 2.4 A resolution. Cyclic non-crystallographic symmetry averaging around the molecular 4-fold axis and phase combination were used to improve the initial multiple isomorphous replacement phases. A model composed of one large subunit and one small subunit was built in the resulting electron density map, which was of excellent quality. Application of the local symmetry gave an initial model of the L8S8 molecule with a crystallographic R-value of 0.43. Refinement of this initial model was performed by a combination of conventional least-squares energy refinement and molecular dynamics simulation using the XPLOR program. Three rounds of refinement, interspersed with manual rebuilding at the graphics display, resulted in a model containing all of the 123 amino acid residues in the small subunit, and 467 of the 475 residues in the large subunit. The R-value for this model is 0.24, with relatively small deviations from ideal stereochemistry. Subunit interactions in the L8S8 molecule have been analysed and are described. The interface areas between the subunits are extensive, and bury almost half of the accessible surface areas of both the large and the small subunit. A number of conserved interaction areas that may be of functional significance have been identified and are described, and biochemical and mutagenesis data are discussed in the structural framework of the model.
J Mol Biol 1990 Sep 05
PMID:Crystallographic analysis of ribulose 1,5-bisphosphate carboxylase from spinach at 2.4 A resolution. Subunit interactions and active site. 211 58

Proton nuclear magnetic resonance was used to follow glucose metabolism in Giardia lamblia. Under strictly anaerobic conditions this organism produces equimolar ethanol and alanine as well as CO2 and some acetate. Aerobically the production of both alanine and ethanol are inhibited and more acetate and CO2 are formed. These changes in the balance of products are reversible over the range 0-46 microM O2. In the presence of 46 microM O2, alanine was not detectable. The O2-sensitivity of alanine production may highlight the necessity for redox-balancing reactions in an organism exposed in situ to fluctuating concentrations of O2.
Mol Biochem Parasitol 1990 Aug
PMID:Giardia lamblia produces alanine anaerobically but not in the presence of oxygen. 212 48

The effect of changes of pHi on Cai were studied using fluorescent dyes in cells of the cultured smooth muscle-like line, BC3H-1. Resting Cai in these cells was 182 +/- 12 nM (n = 74) at pHo of 7.4. Upon exposure to NH4Cl, which rapidly alkalinized cells, a transient increase of Cai to 394 +/- 55 nM (n = 29) was observed. The peak of the transient occurred within 30 s of exposure to NH4Cl and returned to baseline within 1 minute. Two other procedures which resulted in rapid cellular alkalinization also caused a transient rise in Cai: exposure to and then removal of CO2 (Cai increased from 182 +/- 22 to 248 +/- 28 nM; n = 8); and exposure to and then removal of Na propionate (Cai increased from 242 +/- 32 to 456 +/- 71 nM; n = 9). The NH4Cl-induced Cai transient was eliminated by exposure to 0.2 mM TMB8 and to Ca-free solutions, but not by exposure to 0.5 mM LaCl3. Sustained changes of pHi can be induced by varying pHo. When pHo was lowered to 6.9, Cai fell by 49 +/- 11 nM but increased by 203 +/- 51 nM (n = 6) when pHo was raised to 7.9. These data indicate that rapid alkalinization of BC3H-1 cells results in a rapid transient rise of Cai. This transient is most likely due to the release of Ca from intracellular stores but may also involve an increase of Ca influx. Steady state values of Cai are positively correlated with steady state pHi. These data may have implications for the contractile state of smooth muscle during periods of acid/base disturbances and relate to the role of elevated pHi in cells from hypertensive animals.
Mol Cell Biochem 1990 Dec 20
PMID:Effect of changes of pHi on intracellular calcium in a smooth muscle-like cell line. 212 45

In ischemic myocardium abnormal lipid metabolism results in accumulation of compounds that are deleterious to membrane structural integrity and membrane dependent functions. In this study isolated adult rat ventricular myocytes were used to investigate anoxia-induced alterations in cellular lipid composition and metabolism. Myocyte phospholipid content declined 19% on average during 60 min anoxia and intracellular arachidonic acid increased 3-fold, without affecting myocyte ATP content. Anaerobic incubation in the absence of glucose depleted cellular ATP to 2 nmol/mg protein, elicited a 23% decrease in phospholipids, and reduced triacylglycerol content by 51%. Intracellular levels of C16-C22 fatty acids were significantly elevated, especially palmitic and arachidonic acids. Myocytes presented with 0.08 mM [1-14C]-palmitic or arachidonic acid acylated 85% (25-26 nmol/mg) of the fatty acid taken up into triacylglycerols. Anoxia decreased this esterification by 46-60%. Formation of [14C]-CO2 was also depressed 70-90% by anaerobiosis. The results demonstrate that anoxia stimulates degradation of complex lipids, with a concomitant increase in non-esterified fatty acids, especially arachidonic acid.
J Mol Cell Cardiol 1990 Dec
PMID:The effect of anoxia on lipid metabolism in isolated adult rat cardiac myocytes. 212 22


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