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PubMed2001

Fingerprinting of polysaccharides attacked by hydroxyl radicals in vitro and in the cell walls of ripening pear fruit.

Hydroxyl radicals (*OH) may cause non-enzymic scission of polysaccharides in vivo, e.g. in plant cell walls and mammalian connective tissues. To provide a method for detecting the action of endogenous *OH in vivo, we investigated the products formed when polysaccharides were treated with *OH (generated in situ by ascorbate-H(2)O(2)-Cu(2+) mixtures) followed by NaB(3)H(4). Treatment with *OH increased the number of NaB(3)H(4)-reacting groups present in citrus pectin, homogalacturonan and tamarind xyloglucan. This increase is attributed partly to the formation of glycosulose and glycosulosuronic acid residues, which are then reduced back to the original (but radioactive) sugar residues and their epimers by NaB(3)H(4). The glycosulose and glycosulosuronic acid residues were stable for >16 h at 20 degrees C in ethanol or buffer (pH 4.7), but were destroyed in alkali. Driselase-digestion of the radiolabelled polysaccharides yielded characteristic patterns of (3)H-products, which included galactose and galacturonate from pectin, and isoprimeverose, galactose, glucose and arabinose from xyloglucan. Pectin yielded at least eight (3)H-labelled anionic products, separable by electrophoresis at pH 3.5. The patterns of radioactive products form useful 'fingerprints' by which *OH-attacked polysaccharides may be recognized. Applied to the cell walls of ripening pear (Pyrus communis) fruit, the method gave evidence for progressive *OH radical attack on polysaccharides during the softening process.

Cell Wall↗

PubMed1975

Glucose analogs as potential diagnostic tracers for brain tumors.

No tumor-specific tracer has yet been found for the detection of brain tumors by external scintiscanning. Glucose is a substrate in high demand by almost all tumors, and therefore an investigation was undertaken into the potential value of glucose and its analogs as tracers for brain tumors. The compounds studied were D-)1-3H)glucose, D-(1-14C)glucose, (3H)3-O-methyl-D-glucose and L-(1-14C)glucose. The tracers were injected i.v. into C57BL/6J mice carrying a transplantable s.c. ependymoblastoma. At specific time intervlas after injection, mice were sacrificed and the radioactivity of 6 tissues including tumor and brain were assayed by means of an automated combustion technique and liquid scintillation counting. Tumor uptake, expressed as percentage mean body concentration, was 60% for 2 of the tracers, and 92 and 143%, respectively, for 2 others. Brain uptake was over 130% mean body concentration, with 3 of the 4 tracers studies. With L-glucose, brain uptake was only 15.4% mean body concentration, and a maximum tumor-to-brain ratio of 9.5 was achieved. The very high tumor uptake achieved with two of these carbohydrated demonstrates that a carbohydrate analog may be found that shows high tumor specificity and uptake, and that may be useful for external scintiscanning.

Animals↗

PubMed1982

Glycogen metabolism in the liver of the neonatal gsd/gsd and control (GSD/GSD) rat.

1. The metabolism of hepatic glycogen, labelled with [6-3H]glucose at day 19.5 of gestation and with 14C from [U-14C]galactose at delivery, was followed for 10 h in food-deprived gsd/gsd and control (GSD/GSD) neonatal rats. 2. In the affected pups glycogen was maintained at 12% (w/w) and there was no loss of incorporated radioactivity. 3. The 3H and 14C in glycogen from the controls were both decreased by 80%, but 14C was removed at 0--5 h and [6-3H]glucose at 5--10 h. 4. Blood glucose concentrations in the unaffected neonatal rats fell from 5.3 mM at 20 min to 1.7 mM after 10 h. In the gsd/gsd pups blood glucose concentration was decreased from 2 mM at birth to 0.3 mM at 2.5 h: it was maintained at 0.8 mM between 5 and 10 h. 5. In neonatal rats that had been dead for 10 h, hepatic glycogen was decreased by 34% in the controls and by 22% in the gsd/gsd pups. These results demonstrate that liver from the affected rats contains glycogenolytic activity, but that it is not expressed in living tissue.

Animals↗

PubMed2002

A fluorescent compound for glucose uptake measurements in isolated rat cardiomyocytes.

A focus of current diabetes research is the development of insulinomimetic compounds for oral treatment of diabetes and its associated cardiac complications. Screening compounds for their potential insulinomimetic effects usually involves the use of radioactive isotopes. The focus of this study was to investigate a nonradioactive fluorescent compound for its use in screening insulinomimetic compounds. The indicator 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) has been used by some workers to measure glucose uptake in Escherichia coli and Candida albicans. We propose that 2-NBDG will also be a suitable indicator for mammalian cell lines, in particular rat cardiomyocytes. We found that the indicator could give a reliable reproducible standard curve following appropriate dilution and is taken up by isolated cardiomyocytes. The insulinomimetic compounds vanadyl sulfate and sodium molybdate showed rates of glucose uptake similar to that of insulin. Furthermore, the rate of uptake measured for insulin using this technique (0.04 +/- 0.003 nmol x min(-1) x 10(6) cells(-1) is comparable with previous literature using 2-deoxyglucose uptake measurements on isolated myocytes (0.040 nmol x min(-1) x 10(6) cells(-1), demonstrating the validity of this fluorescent compound for glucose uptake studies.

4-Chloro-7-nitrobenzofurazan↗

PubMed1970

The metabolism of gamma-aminobutyrate and glucose in potassium ion-stimulated brain tissue in vitro.

1. The metabolism of gamma-aminobutyrate (GABA) was investigated in cerebral-cortex slices incubated in glucose-saline medium with [1-(14)C]GABA and [U-(14)C]-glucose as labelled substrates. 2. A rapid release of GABA from the tissue, amounting to 25-30% of the total, was observed on addition of 66m-equiv. of K(+)/1 to the medium; the liberation of other amino acids was relatively small. The effect was apparently specific for K(+); GABA was not released on addition of equivalent amounts of Na(+) or on increasing the respiration rate with 10mm-ammonium chloride. The results show that GABA behaves like the transmitter compounds (acetylcholine, catecholamines) on K(+) stimulation, and therefore now satisfies certain of the criteria required for a transmitter in mammalian brain. 3. The release of GABA from the tissue on addition of K(+) was followed by a slow re-uptake. The rate of uptake of GABA in a medium containing 5.9m-equiv. of K(+)/1 was more than four times that in a medium containing 66m-equiv. of K(+)/1. 4. The concentration of GABA in brain tissue incubated for 1h in a medium containing 66m-equiv. of K(+)/1 was about 50% higher than that observed under normal conditions. 5. There was evidence that exogenous [(14)C]GABA mixed with the endogenous pool(s), since the proportion of the total GABA released on K(+) stimulation was the same, and the specific radioactivity of the liberated GABA was close to that remaining in the tissue, whether the GABA was labelled by [1-(14)C]GABA from the medium or generated in the tissue from [(14)C]glucose. 6. On the basis of these findings and the observations outlined in the preceding papers it was possible to calculate the kinetic constants of GABA metabolism by computer simulation of the results. K(+) stimulation led to a 2.5-fold increase in the flux through the tricarboxylic acid cycle, whereas the flux in the GABA bypath was little affected; as a result the flux through the GABA bypath, which under normal conditions was 8% of that through the tricarboxylic acid cycle, decreased to 3-5%. 7. The metabolism of glutamine was greatly affected by K(+)-stimulation. The ratio of the concentration of glutamine in the slices to that in the medium, which under normal conditions was the smallest among the amino acids investigated, increased from about 17 to 63 in 1h. This effect was attributable partly to an uptake of glutamine from the medium (1.8mumol/h per g) and partly to a net increase in the total amount of glutamine (2.6mumol/h per g). At 1h after the addition of K(+) the net gain of glutamine could be accounted for by the decrease of glutamate. 8. Metabolic compartmentation was evident when brain-cortex slices were incubated in glucose-saline medium and the labelled substrate was [(14)C]GABA, since the specific radioactivity of glutamine exceeded that of glutamate. On addition of K(+) the signs of metabolic compartmentation promptly disappeared: this effect was apparently associated with an increase in the permeability of the compartments containing labelled metabolites derived from [(14)C]GABA. The change in the permeability, however, did not affect all the compartments; when the labelled substrate was [(14)C]glucose the equilibration of labelled amino acids between tissue and medium was similar under normal conditions and in the presence of high concentrations of K(+). 9. The metabolism of [(14)C]glucose was followed by measuring oxygen uptake, respiratory (14)CO(2), and incorporation of (14)C into amino acids. The results showed that K(+) stimulation increased the flux of glucose carbon, both in the glycolytic pathway and in the tricarboxylic acid cycle.

Amino Acids↗

PubMed1993

Sequential assembly and polymerization of the polyprenol-linked pentasaccharide repeating unit of the xanthan polysaccharide in Xanthomonas campestris.

Lipid-linked intermediates are involved in the synthesis of the exopolysaccharide xanthan produced by the bacterium Xanthomonas campestris (L. Ielpi, R. O. Couso, and M. A. Dankert, FEBS Lett. 130:253-256, 1981). In this study, the stepwise assembly of the repeating pentasaccharide unit of xanthan is described. EDTA-treated X. campestris cells were used as both enzyme preparation and lipid-P acceptor, and UDP-Glc, GDP-Man, and UDP-glucuronic acid were used as sugar donors. A linear pentasaccharide unit is assembled on a polyprenol-P lipid carrier by the sequential addition of glucose-1-P, glucose, mannose, glucuronic acid, and mannose. The in vitro synthesis of pentasaccharide-P-P-polyprenol was also accompanied by the incorporation of radioactivity into a polymeric product, which was characterized as xanthan, on the basis of gel filtration and permethylation studies. Results from two-stage reactions showed that essentially pentasaccharide-P-P-polyprenol is polymerized. In addition, the direction of chain elongation has been studied by in vivo experiments. The polymerization of lipid-linked repeat units occurs by the successive transfer of the growing chain to a new pentasaccharide-P-P-polyprenol. The reaction involves C-1 of glucose at the reducing end of the polyprenol-linked growing chain and C-4 of glucose at the nonreducing position of the newly formed polyprenol-linked pentasaccharide, generating a branched polymer with a trisaccharide side chain.

Carbohydrate Sequence↗

PubMed1998

A cell-based potency assay for insulin-like growth factor-I.

The authors developed a cell-based bioassay for determining the potency of recombinant human insulin-like growth factor I (IGF-I) using HU-3 human megakaryoblastic cell line. Cell proliferation was measured using the alamarBlue fluorescence method. The addition of IGF-I resulted in a dose-dependent growth response after 48 hours under serum-free conditions. The effective range was 0.1-25 ng/ml with half-maximal response at approximately 2 ng/ml IGF-I. The assay is simple, requiring just three steps, performed in 96-well microtitre plates and is able to detect changes in activity of truncated analogues of IGF-I (such as des-Gly-IGF-I, des-Gly-Pro-IGF-I and des-Gly-Pro-Glu-IGF-I) as well as IGF-I samples that had been subjected to proteolytic or disulfide reduction treatments. This assay is precise, with interassay variability of less than 10% and accurate, with percentage recoveries of nearly 100%. The relative efficacies of other insulin-related peptides in stimulating cell growth of the cell line were examined. IGF-II was 5-fold less potent than IGF-I and insulin had little or no proliferative activity. In addition, the growth-promoting activity correlated well with IGF-I stimulation of glucose consumption in this system. In conclusion, the HU-3 human megakaryoblastic cell line constitutes a simple system for measuring the biological activity of recombinant IGF-I in quality control set-up. The safety, convenience and precision of the assay make it an attractive alternative to radioactive and other colorimetric methods.

Biological Assay↗

PubMed1986

Utilization of pyruvate and pyruvate precursors by normal and carcinogen-altered rat tracheal epithelial cells in culture.

The metabolism of [14C]pyruvate, [14C]glucose, [14C]glutamine and [14C]alanine was compared between normal rat tracheal epithelial cells and carcinogen-altered cells derived from dimethylbenz(a)anthracene-exposed tracheal implants. Normal primary cultures (NPC) of tracheal cells are distinguished by their need for pyruvate-supplemented medium for growth and survival. The altered cells were selected out by their survival in the unsupplemented medium. Compared to the selected primary cultures (SPC), the NPC showed a three- to four-fold higher incorporation of radioactivity from [2-14C]pyruvate in all the macromolecular fractions, as well as in all the metabolites isolated from the acid soluble fraction and from lactic acid isolated from the medium. [U-14C]glucose was also incorporated at higher levels into lactic acid isolated from the acid soluble fraction and the medium of NPC. These data indicate a higher rate of glycolysis in the normal tracheal cells. This was supported by the findings of a two-fold greater glucose consumption and two-fold higher production of lactic acid isolated from the NPC medium. Lactate dehydrogenase activity was also two-fold higher in NPC. Thus, despite the apparently higher level of pyruvate production in the NPC, exogenous pyruvate is necessary to satisfy the metabolic needs of NPC. The utilization of [U-14C]glutamine or [U-14C]alanine was not markedly different between NPC and SPC. Furthermore, radioactivity from both of the amino acids was recovered in lactic acid in the medium, indicating that both cell types can derive pyruvic acid from either glutamine or alanine. SPC apparently do not use these routes to supply higher levels of pyruvic acid for survival in culture. The oxidation of none of the radioactive metabolites into CO2 was distinctly different between NPC and SPC except for the 1.7-fold higher utilization of [1-14C]glucose along the oxidative arm of the pentose cycle in the normal cells.

Alanine↗

PubMed1987

Galactose metabolism in transferase-deficient galactosaemic and normal long-term lymphoid cell lines.

The activity (mean +/- SD) of galactose-1-phosphate uridyl transferase in two long-term lymphoid cell lines from Caucasian patients with transferase deficiency galactosaemia, a heterozygote, and eight normal subjects was 0, 78 and 168 +/- 55 nmol UDPG consumed (mg protein)-1h-1, respectively. Also, no activity was found in erythrocytes and cultured fibroblasts from the patients. A small number of cells of the galactosaemic lines cultured in medium, in which galactose was substituted for glucose, survived for 37 days. Normal and galactosaemic lines incubated with D-galactose-[1-14C] liberated 218.2 +/- 65.6 and 18.1 pmol 14CO2 (mg cellular protein)-1 (6h)-1, respectively. The evolution of 14CO2 from D-glucose-[1-14C] was similar in normal and galactosaemic lines. In the presence of [3H]galactose the radioactivity incorporated into TCA-precipitated material of the galactosaemic lines was 6.8% of the normal lines. Approximately 26% and 1.3% of the total radioactivity was incorporated into molecular species with a molecular weight greater than 400,000 daltons in normal and galactosaemic cells, respectively. Similar molecules were identified in the cell-free medium of both normal and deficient cells except for an 18,000 daltons molecule identified only in the medium of the normal cells. These findings indicate that a small amount of galactose is metabolized in galactosaemic lines with no transferase activity.

Carbon Dioxide↗

PubMed1980

Fatty acid synthesis in vivo and hepatic contribution to whole-body lipogenic rates in obese Zucker rats.

We have re-examined the claim by Godbole and York, based on the effect of surgical hepatectomy (Diabetologia 14:191, 1978), that liver contributed more than 90% of the newly synthesized FA found in adipose tissue of obese rats at the end of a 1-hr pulse of 3H2O. The amount of newly synthesized FA transported via plasma VLDL from liver to adipose tissue was estimated in lean and obese Zucker rats by determining the effects of Triton WR-1339, which blocks the uptake of VLDL-TGFA into tissues. Triton treatment was found not to cause any significant change in the amount of radioactive FA found in subcutaneous/perimetrial fat tissues, carcass or liver in either chow-fed or high-glucose, fed-refed lean or obese rats, although in the fed-refed dietary state the proportion found in the liver was increased over that in the chow-fed groups. Furthermore, the amounts of newly made FA which accumulated in the plasma of Triton-treated, chow-fed and glucose-fed refed animals during this period constituted only a few percentages of those found in the adipose tissue of these animals. Thus, in contrast to the claims of Godbole and York, no significant transfer of newly made FA from liver to adipose tissue occurs during a 1-hr experiment; it follows that the amount of these FA found in different tissues at the end of that period are valid measurements of their actual lipogenic activities in situ. It is suggested that the Godbole and York results are artifacts of their surgical hepatectomy procedure.

Adipose Tissue↗

PubMed2005

Activation of opioid mu-receptors by loperamide to improve interleukin-6-induced inhibition of insulin signals in myoblast C2C12 cells.

AIMS/HYPOTHESIS: This study investigated the role of opioid mu-receptor activation in the improvement of insulin resistance. METHODS: Myoblast C2C12 cells were cultured with IL-6 to induce insulin resistance. Radioactive 2-deoxyglucose (2-DG) uptake was used to evaluate the effect of loperamide on insulin-stimulated glucose utilisation. Protein expression and phosphorylation in insulin-signalling pathways were detected by immunoblotting. RESULTS: The insulin-stimulated 2-DG uptake was reduced by IL-6. Loperamide reversed this uptake, and the uptake was inhibited by blockade of opioid mu-receptors. Insulin resistance induced by IL-6 was associated with impaired expression of the insulin receptor (IR), IR tyrosine autophosphorylation, IRS-1 protein content and IRS-1 tyrosine phosphorylation. Also, an attenuated p85 regulatory subunit of phosphatidylinositol 3-kinase, Akt serine phosphorylation and the protein of glucose transporter subtype 4 were observed in insulin resistance. Loperamide reversed IL-6-induced decrement of these insulin signals. CONCLUSIONS/INTERPRETATION: Opioid mu-receptor activation may improve IL-6-induced insulin resistance through modulation of insulin signals to reverse the responsiveness of insulin. This provides a new target in the treatment of insulin resistance.

Animals↗

PubMed1992

Purification and characterization of iotrochotin, a novel toxin from the Caribbean sponge Iotrochota birotulata, which selectively permeabilizes synaptosomes.

A protein termed iotrochotin (IOT) was isolated from the exudate of the Caribbean sponge Iotrochota birotulata using as an assay its stimulation of the release of radioactivity from synaptosomes preloaded with [3H]choline. Sephadex G-50 chromatography of the exudate produced one peak, with a mol. wt of approximately 18,000, which was further resolved into two active fractions by anion exchange chromatography. The more tightly bound of the two fractions was characterized and referred to as IOT. The action of IOT was essentially complete by 0.5-1.0 min and was independent of the Ca2+ or Na+ content of the incubation mixture. Released radioactivity included about 50% each of [3H]acetylcholine and [3H]choline. Release of radioactivity increased as a function of IOT concentration and then reached a maximum. Extrapolated asymptotic release was nearly equal to that obtained by lysing the synaptosomes. IOT also released radioactivity from synaptosomes which had been preincubated with other tritiated neurotransmitters or with 2-[3H]deoxy-D-glucose. Lactate dehydrogenase and choline acetyltransferase activities were not released from synaptosomes by treatment with IOT, but were released by digitonin. IOT therefore releases some of the smaller molecular weight components of synaptosomes, but does not permeabilize the synaptosomal membrane in the same way as digitonin treatment.

Animals↗

PubMed2005

Am-241 remobilization in a calcareous soil under simplified rhizospheric conditions studied by column experiments.

The effects of simplified rhizospheric conditions on the leaching of (241)Am from a calcareous soil, freshly contaminated, were investigated in batch and column experiments. Glucose and/or citrate were used as artificial exudate solutions at concentrations ranging from 10(-4) to 10(-2)moldm(-3). Am desorption, expressed in terms of distribution coefficients, varied from K(d)>10(4)dm(3)kg(-1) corresponding to a majority of experimental conditions, to K(d)</=10(2)dm(3)kg(-1) when citrate combined or not with glucose was used at >/=10(-2)moldm(-3). Soil columns revealed successive steady states coupled with transitory episodes, the latter represented up to 90% of the total Am release. (241)Am fractions with different behaviours were thus highlighted in columns whereas batch only accounted for highest Am mobile fractions. The implications of the different processes are discussed in terms of modelling approach and risk assessment.

Adsorption↗

PubMed1983

The accuracy of measurement required for acceptable estimation of non-steady rates of appearance and disappearance by the tracer method using a two-compartment model.

The two-compartment method for measuring non-steady-state glucose turnover rates was examined by computer simulation and by in vivo experiment. Given perfectly accurate input data, the simulations showed that the calculated turnover rates agreed closely with the true answer (agreement was not perfect however, because of the necessity for interpolation between the observed points). Contaminating the input data with a single erroneous observation of either tracee or tracer concentration produced large, spurious oscillations in the calculated turnover rates, the duration of which was inversely proportional to the frequency with which the infused compartment was sampled. Contaminating the perfect input data with observational noise of a magnitude approximately equal to the known measurement uncertainties showed that the calculations were very sensitive to noise and this was verified by in vivo experiment. It is concluded that non-steady-state glucose kinetics can be successfully measured by the two-compartment technique, but that measurements to an accuracy of at least 1% (coefficient of variation) are required.

Animals↗

PubMed1991

Metabolism of phenanthrene by Phanerochaete chrysosporium.

The white rot fungus Phanerochaete chrysosporium metabolized phenanthrene when it was grown for 7 days at 37 degrees C in a medium containing malt extract, D-glucose, D-maltose, yeast extract, and Tween 80. After cultures were grown with [9-14C]phenanthrene, radioactive metabolites were extracted from the medium with ethyl acetate, separated by high-performance liquid chromatography, and detected by liquid scintillation counting. Metabolites from cultures grown with unlabeled phenanthrene were identified as phenanthrene trans-9,10-dihydrodiol, phenanthrene trans-3,4-dihydrodiol, 9-phenanthrol, 3-phenanthrol, 4-phenanthrol, and the novel conjugate 9-phenanthryl beta-D-glucopyranoside. Identification of the compounds was based on their UV absorption, mass, and nuclear magnetic resonance spectra. Since lignin peroxidase was not detected in the culture medium, these results suggest the involvement of monooxygenase and epoxide hydrolase activity in the initial oxidation and hydration of phenanthrene by P. chrysosporium.

Basidiomycota↗

PubMed1967

Aerobic Heterotrophic Bacterial Populations of Sewage and Activated Sludge: III. Adaptation in a Synthetic Waste.

The nature and behavior of the microbial population developed on a synthetic waste containing salts and sorbitol are compared to that of a treatment-plant activated sludge. The population of the adapted sludge developed on the synthetic waste consisted approximately of only six kinds of bacteria. Experiments with radioactive sorbitol indicate that the microbial population developed on the synthetic waste showed the effects of repression by glucose on the metabolism of sorbitol; in contrast, the activated sludge from a plant treating primarily domestic waste was able to attack both substrates immediately and simultaneously.

Journal Article↗

PubMed2003

Profiling substrate fluxes in the isolated working mouse heart using 13C-labeled substrates: focusing on the origin and fate of pyruvate and citrate carbons.

The availability of genetically modified mice requires the development of methods to assess heart function and metabolism in the intact beating organ. With the use of radioactive substrates and ex vivo perfusion of the mouse heart in the working mode, previous studies have documented glucose and fatty acid oxidation pathways. This study was aimed at characterizing the metabolism of other potentially important exogenous carbohydrate sources, namely, lactate and pyruvate. This was achieved by using (13)C-labeling methods. The mouse heart perfusion setup and buffer composition were optimized to reproduce conditions close to the in vivo milieu in terms of workload, cardiac functions, and substrate-hormone supply to the heart (11 mM glucose, 0.8 nM insulin, 50 microM carnitine, 1.5 mM lactate, 0.2 mM pyruvate, 5 nM epinephrine, 0.7 mM oleate, and 3% albumin). The use of three differentially (13)C-labeled carbohydrates and a (13)C-labeled long-chain fatty acid allowed the quantitative assessment of the metabolic origin and fate of tissue pyruvate as well as the relative contribution of substrates feeding acetyl-CoA (pyruvate and fatty acids) and oxaloacetate (pyruvate) for mitochondrial citrate synthesis. Beyond concurring with the notion that the mouse heart preferentially uses fatty acids for energy production (63.5 +/- 3.9%) and regulates its fuel selection according to the Randle cycle, our study reports for the first time in the mouse heart the following findings. First, exogenous lactate is the major carbohydrate contributing to pyruvate formation (42.0 +/- 2.3%). Second, lactate and pyruvate are constantly being taken up and released by the heart, supporting the concept of compartmentation of lactate and glucose metabolism. Finally, mitochondrial anaplerotic pyruvate carboxylation and citrate efflux represent 4.9 +/- 1.8 and 0.8 +/- 0.1%, respectively, of the citric acid cycle flux and are modulated by substrate supply. The described (13)C-labeling strategy combined with an experimental setup that enables continuous monitoring of physiological parameters offers a unique model to clarify the link between metabolic alterations, cardiac dysfunction, and disease development.

Acetyl Coenzyme A↗

PubMed1987

Maternal factors modulating nutrient transfer to fetus.

Current knowledge of the modulation of maternal-fetal transfer of metabolites is reviewed and new data on the actual placental transport of D-glucose, L-alanine and glycerol in the rat are presented. Twenty-one day pregnant rats were infused with the 14C-labelled substrates throughout the left uterine artery. Radioactivity appearing in fetuses was corrected by the specific dilution of the tracer at maternal arterial plasma and the uterine artery blood flow to estimate placental transfer. This parameter appeared to be 127 mumol X kg-1 fetal b.w. X min-1 for D-glucose, 23 for L-alanine, and 1 for glycerol--values which are much higher than those described for larger species. There is a parallelism between the magnitude of transfer to fetus and arterial concentration in mother for each studied metabolite and actually variations in their plasmatic levels affect this transport process. This is clearly seen in the case of glucose where placental transfer is reduced during fasting hypoglycemia and greatly increased in diabetes. Placental transfer of L-alanine and blood flow to the placenta were reduced in both 48-hour starved and streptozotocin-induced diabetic late pregnant rats. Results show the main role of maternal nutrient concentration as a modulator of their transfer to fetus, the deleterious effect of reductions of uterine blood flow on placental transport of amino acids as well as the small placental transfer of glycerol as compared to either glucose or alanine.

Alanine↗