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PubMed2003

The influence of climate on the oxygen isotopes in tree rings.

Natural variations in the oxygen isotope ratio 18O/16O are occurring in the hydrological cycle as a result of isotope fractionations during evaporation and condensation. These processes imprint a valuable climatic signal in the precipitation, which is stored in ice caps as well as in the cellulose of trees. Recent developments in the continuous-flow analysis of 18O/16O of organic matter now enable a systematic application of this method in tree rings. It becomes possible to build maps of the past oxygen isotope distribution in continental areas, yielding important information on regional climate changes. In this paper, the factors influencing the isotope composition of tree rings are discussed with an example from trees in northern Eurasia. Oxygen isotope values of Larix, Picea and Pinus trees were measured over a large climatic gradient extending from Norway to Siberia. The spatial isotope variations were highly correlated to the annual mean temperature (r2 = 0.84), whereby the slope of the corresponding regression line was 0.35%/degrees C. When considering the changes in 18O/16O during the 20th century, not only the temperature, but also changes in the precipitation patterns have to be considered, in particular the observed increase in the amount of winter precipitation.

Asia↗
PubMed2004

The Piracicaba River basin: isotope hydrology of a tropical river basin under anthropogenic stress.

The stable isotope content of samples of precipitation and of the river water throughout the Piracicaba basin in Brazil was measured over a two-year period. The isotope values of precipitation follow a consistent pattern of relatively depleted values of both deuterium and oxygen 18 during the rainy summers and enriched ones during the dry winters, with all values aligned slightly above the Global Meteoric Water Line. The isotopic composition of the river water throughout the basin shows a remarkable spatial coherence and much smaller scatter of data than those of the precipitation. The isotope composition of river water is close to that of the precipitation in the rainy season, however, with a consistent lower d-excess value by 1/1000-2/1000. This is attributed to evaporative water loss in the basin, in part an expression of the recycling of water due to the anthropogenic activity in the region. The more divergent values are recorded during high-water stages in the rivers. In many cases, the floods during the beginning of the rainy season are characterized by an enrichment of the heavy isotopes and lower d-excess values when compared to the precipitation, with the opposite situation later in the rainy season. This is interpreted as resulting from the watershed/riverflow interaction pattern, and it thus suggests that the isotope composition can monitor the hydrologic situation in the basin and its changes.

Brazil↗
PubMed2006

What are the instrumentation requirements for measuring the isotopic composition of net ecosystem exchange of CO2 using eddy covariance methods?

Better quantification of isotope ratios of atmosphere-ecosystem exchange of CO2 could substantially improve our ability to probe underlying physiological and ecological mechanisms controlling ecosystem carbon exchange, but the ability to make long-term continuous measurements of isotope ratios of exchange fluxes has been limited by measurement difficulties. In particular, direct eddy covariance methods have not yet been used for measuring the isotopic composition of ecosystem fluxes. In this article, we explore the feasibility of such measurements by (a) proposing a general criterion for judging whether a sensor's performance is sufficient for making such measurements (the criterion is met when the contribution of sensor error to the flux measurement error is comparable to or less than the contribution of meteorological noise inherently associated with turbulence flux measurements); (b) using data-based numerical simulations to quantify the level of sensor precision and stability required to meet this criterion for making direct eddy covariance measurements of the 13C/12C ratio of CO2 fluxes above a specific ecosystem (a mid-latitude temperate forest in central Massachusetts, USA); (c) testing whether the performance of a new sensor-a prototype pulsed quantum cascade laser (QCL) based isotope-ratio absorption spectrometer (and plausible improvements thereon)-is sufficient for meeting the criterion in this ecosystem. We found that the error contribution from a prototype sensor (approximately 0.2 per thousand, 1 SD of 10 s integrations) to total isoflux measurement error was comparable to (1.5 to 2x) the irreducible 'meteorological' noise inherently associated with turbulent flux measurements above this ecosystem (daytime measurement error SD of approximately 60% of flux versus meteorological noise of 30-40% for instantaneous half-hour fluxes). Our analysis also shows that plausible instrument improvements (increase of sensor precision to approximately 0.1 per thousand, 1 SD of 10 s integrations, and increased sensor stability during the half-hour needed to integrate eddy covariance measurements) should decrease the contribution of sensor error to the point where it is less than the contribution from meteorological noise. This suggests that new sensors using QCL-based isotope ratio absorption spectroscopy should make continuous long-term observations of the isotopic composition of CO2 fluxes via eddy covariance methods feasible.

Carbon Dioxide↗
PubMed2006

Cerium isotope effects in Ce(III) malate and lactate complex formation studied by long-distance displacement chromatography.

Isotope effects of cerium were observed in malate and lactate complex formations during the long-distance displacement chromatographic processes at 313 K. Heavier isotopes were found fractionated in the frontal edges of the Ce adsorption bands in both the systems, registering a preference of the heavier isotopes for the Ce(III) complexes in the solution phase over the simply hydrated Ce(III) ions in the resin phase. The fractionation coefficients epsilon for the 136Ce/140Ce, 138Ce/140Ce and 142Ce/140Ce isotopic pairs were 7.1 x 10(-6), 5.2 x 10(-6) and -2.1 x 10(-6) for the malate system, and 4.8 x 10(-6), 4.5 x 10(-6) and-2.6 x 10(-6) for the lactate system, respectively. They all show the mass-dependent law if the deviation of epsilon for the 138Ce/140Ce pair was considered merely due to the isobaric interference in Ce isotopic ratio measurements, suggesting the molecular vibration, rather than the nuclear field shift, mainly contributes to the Ce isotope effects in the complex formation systems. The absolute values of epsilon between the two systems are comparable, suggesting no instinct difference in structural properties between Ce malate and lactate complexes involved.

Cerium Isotopes↗
PubMed1991

Bioavailability of dietary minerals to humans: the stable isotope approach.

A number of minerals contained in foods are essential nutrients for humans, animals, and/or plants. While most vitamins are very well absorbed, most essential minerals are not. Usual absorption of minerals ranges from less than 1% to over 90%. The bioavailability of dietary minerals must be considered when determining whether the diet contains enough, too little, or too much. By using stable isotope tracers as labels, the metabolic fate of minerals in a specific day's diet, a specific meal, or a food can be distinguished from minerals from other sources and followed. A number of mass spectrometric methods have been used to measure stable isotopes. Magnetic sector, thermal ionization mass spectrometry (TIMS) is used routinely in our laboratory to study bioavailability of Zn, Cu, and Fe. Other mass spectrometric methods that are less precise, but useful for many applications requiring isotopic determinations include quadrupole TIMS, inductively coupled plasma mass spectrometry (ICP/MS), and fast atom bombardment mass spectrometry (FAB/MS). One of the major advantages of stable isotope studies is that multiple isotopes of the same mineral can be used simultaneously and multiple minerals can be studied simultaneously. The use of stable isotopes for studies of bioavailability of minerals in foods has gained widespread interest in recent years. The approach is expected to be applied to an increasing number of food science and nutrition problems in the future.

Biological Availability↗
PubMed2003

A novel dual radio- and stable-isotope method for measuring calcium absorption in humans: comparison with the whole-body radioisotope retention method.

BACKGROUND: Dietary calcium absorption can be determined only with the use of isotope techniques. Currently used isotope techniques require exclusive equipment or are not true tracer approaches. OBJECTIVE: The objective was to compare a dual-isotope method combining radioisotopes and stable isotopes with a whole-body radioisotope retention method for measuring calcium absorption. DESIGN: Seven healthy adults aged 21-27 y consumed a test meal containing 63 +/- 14 (macro x +/- SD) mg Ca together with a water solution of (47)Ca (0.11 MBq). One hour after ingestion, 18 mg (44)Ca was administered intravenously. All feces and urine were collected for 5 and 6 d, respectively. Calcium absorption was estimated from whole-body retention of the radioisotope 12 times over 3 wk after ingestion and from the excretion of (47)Ca and (44)Ca in a 24-h urine sample collected on day 2. (44)Ca in urine was determined by inductively coupled plasma mass spectrometry. RESULTS: Mean (+/- SD) calcium absorption was 75 +/- 9% with the dual-isotope method and was 74 +/- 8% with the whole-body radioisotope retention method. There was a high degree of agreement between the methods. CONCLUSION: The dual-isotope method is a valid approach for measuring calcium absorption from a single meal.

Administration, Oral↗
PubMed2006

Unusual origins of isotope effects in enzyme-catalysed reactions.

High hydrostatic pressure is a neglected tool for probing the origins of isotope effects. In chemical reactions, normal primary deuterium isotope effects (DIEs) arising solely from differences in zero point energies are unaffected by pressure; but some anomalous isotope effects in which hydrogen tunnelling is suspected are partially suppressed. In some enzymatic reactions, high pressure completely suppresses the DIE. We have now measured the effects of high pressure on the parallel 13C heavy atom isotope effect of yeast alcohol dehydrogenase and found that it is also suppressed by high pressure and, similarly, suppressed in its entirety. Moreover, the volume changes associated with the suppression of both deuterium and heavy atom isotope effects are virtually identical. The equivalent decrease in activation volumes for hydride transfer, when one mass unit is added to the carbon end of a scissile C-H bond as when one mass unit is added to the hydrogen end, suggests a common origin. Given that carbon is highly unlikely to undergo tunnelling, it follows that hydrogen is not doing so either. The origin of these isotope effects must lie elsewhere. We offer protein domain motions as a possibility.

Alcohol Dehydrogenase↗
PubMed2006

Searching for signatures of life on Mars: an Fe-isotope perspective.

Recent spacecraft and lander missions to Mars have reinforced previous interpretations that Mars was a wet and warm planet in the geological past. The role of liquid water in shaping many of the surface features on Mars has long been recognized. Since the presence of liquid water is essential for survival of life, conditions on early Mars might have been more favourable for the emergence and evolution of life. Until a sample return mission to Mars, one of the ways of studying the past environmental conditions on Mars is through chemical and isotopic studies of Martian meteorites. Over 35 individual meteorite samples, believed to have originated on Mars, are now available for lab-based studies. Fe is a key element that is present in both primary and secondary minerals in the Martian meteorites. Fe-isotope ratios can be fractionated by low-temperature processes which includes biological activity. Experimental investigations of Fe reduction and oxidation by bacteria have produced large fractionation in Fe-isotope ratios. Hence, it is considered likely that if there is/were any form of life present on Mars then it might be possible to detect its signature by Fe-isotope studies of Martian meteorites. In the present study, we have analysed a number of Martian meteorites for their bulk-Fe-isotope composition. In addition, a set of terrestrial analogue material has also been analysed to compare the results and draw inferences. So far, our studies have not found any measurable Fe-isotopic fractionation in bulk Martian meteorites that can be ascribed to any low-temperature process operative on Mars.

Biological Evolution↗
PubMed2006

High-density lipoprotein apolipoprotein A-I kinetics: comparison of radioactive and stable isotope studies.

To compare the kinetic determinants of high-density lipoprotein (HDL) apolipoprotein A-I (apoA-I) concentration in lean normolipidaemic subjects using radioisotope and stable isotope studies. We pooled data from 16 radioisotope and 13 stable isotope studies to investigate the kinetics of apoA-I in lean normolipidemic individuals. We also examined the associations of HDL kinetic parameters with age, sex, body mass index (BMI) and concentrations of apoA-I, triglycerides, HDL cholesterol and low-density lipoprotein (LDL) cholesterol. Lean subjects from radioisotope and stable isotope studies were matched for age, gender, BMI and lipid profile. The apoA-I concentration was significantly lower in the radioisotope group than the stable isotope group (P = 0.031). There was no significant difference in HDL apoA-I fractional catabolic rate (FCR) and production rate (PR) between the groups. In the radioisotope group, HDL apoA-I FCR was significantly associated with apoA-I and HDL cholesterol concentrations (r = -0.681, P < 0.001 and r = -0.542, P < 0.001, respectively), whereas in the stable isotope group, only HDL apoA-I PR was significantly associated with apoA-I concentration (r = 0.455, P = 0.004). Our findings suggest that HDL apoA-I FCR is the primary determinant of apoA-I concentrations in lean subjects in studies using radiotracer techniques. By contrast, HDL apoA-I PR is the primary determinant of apoA-I concentration in lean subject in studies employing stable isotope methods. These discrepancies may be reconciled by differences in methodologies and/or study population characteristics.

Adolescent↗
PubMed2006

Contributions of evaporation, isotopic non-steady state transpiration and atmospheric mixing on the delta18O of water vapour in Pacific Northwest coniferous forests.

Changes in the 2H and 18O of atmospheric water vapour provide information for integrating aspects of gas exchange within forest canopies. In this study, we show that diurnal fluctuations in the oxygen isotope ratio (delta 18O) as high as 4% per hundred were observed for water vapour (delta (18)Ovp) above and within an old-growth coniferous forest in the Pacific Northwest region of the United States. Values of delta 18Ovp decreased in the morning, reached a minimum at midday, and recovered to early-morning values in the late afternoon, creating a nearly symmetrical diurnal pattern for two consecutive summer days. A mass balance budget was derived and assessed for the 18O of canopy water vapour over a 2-d period by considering the 18O-isoflux of canopy transpiration, soil evaporation and the air entering the canopy column. The budget was used to address two questions: (1) do delta 18O values of canopy water vapour reflect the biospheric influence, or are such signals swamped by atmospheric mixing? and (2) what mechanisms drive temporal variations of delta 18Ovp? Model calculations show that the entry of air into the canopy column resulted in an isotopically depleted 18O-isoflux in the morning of day 1, causing values of delta 18Ovp, to decrease. An isotopically enriched 18O-isoflux resulting from transpiration then offset this decreased delta 18Ovp later during the day. Contributions of 18O-isoflux from soil evaporation were relatively small on day 1 but were more significant on day 2, despite the small H2(16)O fluxes. From measurements of leaf water volume and sapflux, we determined the turnover time of leaf water in the needles of Douglas-fir trees as approximately 11 h at midday. Such an extended turnover time suggests that transpiration may not have occurred at the commonly assumed isotopic steady state. We tested a non-steady state model for predicting delta 18O of leaf water. Our model calculations show that assuming isotopic steady state increased isoflux of transpiration. The impact of this increase on the modelled delta 18Ovp was clearly detectable, suggesting the importance of considering isotopic non-steady state of transpiration in studies of forest 18O water balance.

Atmosphere↗
PubMed2006

Variation in oxygen isotope fractionation during cellulose synthesis: intramolecular and biosynthetic effects.

The oxygen isotopic composition of plant cellulose is commonly used for the interpretations of climate, ecophysiology and dendrochronology in both modern and palaeoenvironments. Further applications of this analytical tool depends on our in-depth knowledge of the isotopic fractionations associated with the biochemical pathways leading to cellulose. Here, we test two important assumptions regarding isotopic effects resulting from the location of oxygen in the carbohydrate moiety and the biosynthetic pathway towards cellulose synthesis. We show that the oxygen isotopic fractionation of the oxygen attached to carbon 2 of the glucose moieties differs from the average fractionation of the oxygens attached to carbons 3-6 from cellulose by at least 9%, for cellulose synthesized within seedlings of two different species (Triticum aestivum L. and Ricinus communis L.). The fractionation for a given oxygen in cellulose synthesized by the Triticum seedlings, which have starch as their primary carbon source, is different than the corresponding fractionation in Ricinus seedlings, within which lipids are the primary carbon source. This observation shows that the biosynthetic pathway towards cellulose affects oxygen isotope partitioning, a fact heretofore undemonstrated. Our findings may explain the species-dependent variability in the overall oxygen isotope fractionation during cellulose synthesis, and may provide much-needed insight for palaeoclimate reconstruction using fossil cellulose.

Cellulose↗
PubMed1979

Deuterium isotope effects on papain acylation. Evidence for lack of general base catalysis and for enzyme--leaving-group interaction.

The experimental data presented in this paper comprise kinetic deuterium isotope effects on acylation of papain with various substrates when conducted in H2O and 2H2O. With alkyl esters of N-acylamino acids there is no or very little isotope effect, whereas with N-acylamino acid amides the ratio kappa H2O/kappa 2H2O is less than 1, i.e. there is an inverse isotope effect. Similarly, alkylation of papain with methyl bromoacetate exhibits no kinetic isotope effect, whereas for the analogous alkylation with bromoacetamide an inverse isotope effect is observed. It is concluded that (a) general base catalysis does not occur in the acylation of papain and (b) kinetic deuterium isotope effects can be affected substantially by interaction between the substrate leaving group and the enzyme, which has not been considered in previous mechanistic investigations.

Acylation↗
PubMed2005

Isotopic discrimination of zinc in higher plants.

* The extent of isotopic discrimination of transition metals in biological processes is poorly understood but potentially has important applications in plant and biogeochemical studies. * Using multicollector inductively coupled plasma (ICP) mass spectrometry, we measured isotopic fractionation of zinc (Zn) during uptake from nutrient solutions by rice (Oryza sativa), lettuce (Lactuca sativa) and tomato (Lycopersicon esculentum) plants. * For all three species, the roots showed a similar extent of heavy Zn enrichment relative to the nutrient solution, probably reflecting preferential adsorption on external root surfaces. By contrast, a plant-species specific enrichment of the light Zn isotope occurred in the shoots, indicative of a biological, membrane-transport controlled uptake into plant cells. The extent of the fractionation in the shoots further depended on the Zn speciation in the nutrient solution. * The observed isotopic depletion in heavy Zn from root to shoot (-0.13 to -0.26 per atomic mass unit) is equivalent to roughly a quarter of the total reported terrestrial variability of Zn isotopic compositions (c. 0.84 per atomic mass unit). Plant uptake therefore represents an important source of isotopic variation in biogeochemical cycling of Zn.

Biological Transport↗
PubMed2006

Kinetic deuterium isotope effects for 7-alkoxycoumarin O-dealkylation reactions catalyzed by human cytochromes P450 and in liver microsomes. Rate-limiting C-H bond breaking in cytochrome P450 1A2 substrate oxidation.

7-Ethoxy (OEt) coumarin has been used as a model substrate in many cytochrome P450 (P450) studies, including the use of kinetic isotope effects to probe facets of P450 kinetics. P450s 1A2 and 2E1 are known to be the major catalysts of 7-OEt coumarin O-deethylation in human liver microsomes. Human P450 1A2 also catalyzed 3-hydroxylation of 7-methoxy (OMe) coumarin at appreciable rates but P450 2E1 did not. Intramolecular kinetic isotope effects were used as estimates of the intrinsic kinetic deuterium isotope effects for both 7-OMe and 7-OEt coumarin dealkylation reactions. The apparent intrinsic isotope effect for P450 1A2 (9.4 for O-demethylation, 6.1 for O-deethylation) showed little attenuation in other competitive and noncompetitive experiments. With P450 2E1, the intrinsic isotope effect (9.6 for O-demethylation, 6.1 for O-deethylation) was attenuated in the noncompetitive intermolecular experiments. High noncompetitive intermolecular kinetic isotope effects were seen for 7-OEt coumarin O-deethylation in a baculovirus-based microsomal system and five samples of human liver microsomes (7.3-8.1 for O-deethylation), consistent with the view that P450 1A2 is the most efficient P450 catalyzing this reaction in human liver microsomes and indicating that the C-H bond-breaking step makes a major contribution to the rate of this P450 (1A2) reaction. Thus, the rate-limiting step appears to be the chemistry of the breaking of this bond by the activated iron-oxygen complex, as opposed to steps involved in the generation of the reactive complex. The conclusion about the rate-limiting step applies to all of the systems studied with this model P450 1A2 reaction including human liver microsomes, the most physiologically relevant.

7-Alkoxycoumarin O-Dealkylase↗
PubMed2003

Stable carbon isotope fractionation by sulfate-reducing bacteria.

Biogeochemical transformations occurring in the anoxic zones of stratified sedimentary microbial communities can profoundly influence the isotopic and organic signatures preserved in the fossil record. Accordingly, we have determined carbon isotope discrimination that is associated with both heterotrophic and lithotrophic growth of pure cultures of sulfate-reducing bacteria (SRB). For heterotrophic-growth experiments, substrate consumption was monitored to completion. Sealed vessels containing SRB cultures were harvested at different time intervals, and delta(13)C values were determined for gaseous CO(2), organic substrates, and products such as biomass. For three of the four SRB, carbon isotope effects between the substrates, acetate or lactate and CO(2), and the cell biomass were small, ranging from 0 to 2 per thousand. However, for Desulfotomaculum acetoxidans, the carbon incorporated into biomass was isotopically heavier than the available substrates by 8 to 9 per thousand. SRB grown lithoautotrophically consumed less than 3% of the available CO(2) and exhibited substantial discrimination (calculated as isotope fractionation factors [alpha]), as follows: for Desulfobacterium autotrophicum, alpha values ranged from 1.0100 to 1.0123; for Desulfobacter hydrogenophilus, the alpha value was 0.0138, and for Desulfotomaculum acetoxidans, the alpha value was 1.0310. Mixotrophic growth of Desulfovibrio desulfuricans on acetate and CO(2) resulted in biomass with a delta(13)C composition intermediate to that of the substrates. The extent of fractionation depended on which enzymatic pathways were used, the direction in which the pathways operated, and the growth rate, but fractionation was not dependent on the growth phase. To the extent that environmental conditions affect the availability of organic substrates (e.g., acetate) and reducing power (e.g., H(2)), ecological forces can also influence carbon isotope discrimination by SRB.

Biomass↗
PubMed2005

Stable isotope fractionation of tetrachloroethene during reductive dechlorination by Sulfurospirillum multivorans and Desulfitobacterium sp. strain PCE-S and abiotic reactions with cyanocobalamin.

Carbon stable isotope fractionation of tetrachloroethene (PCE) during reductive dechlorination by whole cells and crude extracts of Sulfurospirillum multivorans and Desulfitobacterium sp. strain PCE-S and the abiotic reaction with cyanocobalamin (vitamin B12) was studied. Fractionation was largest during the reaction with cyanocobalamin with alphaC = 1.0132. Stable isotope fractionation was lower but still in a similar order of magnitude for Desulfitobacterium sp. PCE-S (alphaC = 1.0052 to 1.0098). The isotope fractionation of PCE during dehalogenation by S. multivorans was lower by 1 order of magnitude (alphaC = 1.00042 to 1.0017). Additionally, an increase in isotope fractionation was observed with a decrease in cell integrity for both strains. For Desulfitobacterium sp. strain PCE-S, the carbon stable isotope fractionation factors were 1.0052 and 1.0089 for growing cells and crude extracts, respectively. For S. multivorans, alphaC values were 1.00042, 1.00097, and 1.0017 for growing cells, crude extracts, and the purified PCE reductive dehalogenase, respectively. For the field application of stable isotope fractionation, care is needed as fractionation may vary by more than an order of magnitude depending on the bacteria present, responsible for degradation.

Bacteria, Aerobic↗
PubMed2002

Underestimation of gluconeogenesis by the [U-(13)C(6)]glucose method: effect of lack of isotope equilibrium.

Among the many tracer methods to indirectly estimate gluconeogenesis in humans, the [U-(13)C(6)]glucose method as proposed by Tayek and Katz (Am J Physiol Endocrinol Metab 270: E709-E717, 1996; Am J Physiol Endocrinol Metab 272: E476-E484, 1997) has the advantage of being able to simultaneously estimate hepatic glucose output and fractional gluconeogenesis. However, Landau et al. (Landau BR, J Wahren, K Ekberg, SF Previs, D Yang, and H Brunengraber. Am J Physiol Endocrinol Metab 274: E954-E961, 1998) have shown that this method underestimates the rate of gluconeogenesis. The underestimation has been attributed to tracer dilution by other three-carbon substrates and the lack of isotopic steady state. Using a computer simulation of [U-(13)C(6)]glucose infusion, we demonstrate that the lack of isotope equilibrium in both the lactate and glucose compartments contributes substantially to the underestimation of gluconeogenesis. [U-(13)C(6)]glucose experiments were performed with the addition of a primed constant infusion of [U-(13)C(3)]lactate and the delay in M3 glucose equilibrium estimated from the isotopic steady-state value determined by modeling M3 glucose to a single-exponential fit. We found that, even with the addition of [U-(13)C(3)]lactate infusion, the M3 glucose enrichment of the last timed sample was approximately 20% less than the isotopic steady-state value. Thus the lack of isotopic equilibrium of the glucose compartment potentially accounts for 20% of the underestimation of gluconeogenesis. The underestimation of gluconeogenesis using [U-(13)C(6)]glucose without the additional infusion of [U-(13)C(3)]lactate in previous publications is expected to be even greater because of the lack of isotope equilibrium in both the lactate and glucose compartments. These findings are consistent with the results from our computer simulation.

Carbon Isotopes↗
PubMed1986

A dual-isotope technique for determination of in vivo ketone body kinetics.

"Total ketone body specific activity" has been widely used in studies of ketone body metabolism to circumvent so-called "isotope disequilibrium" between the two major ketone body pools, acetoacetate and beta-hydroxybutyrate. Recently, this approach has been criticized on theoretical grounds. In the present studies, [13C]acetoacetate and beta-[14C]hydroxybutyrate were simultaneously infused in nine mongrel dogs before and during an infusion of either unlabeled sodium acetoacetate or unlabeled sodium beta-hydroxybutyrate. Ketone body turnover was determined using total ketone body specific activity, total ketone body moles % enrichment, and an open two-pool model, both before and during the exogenous infusion of unlabeled ketone bodies. Basal ketone body turnover rates were significantly higher using [13C]acetoacetate than with either beta-[14C]hydroxybutyrate alone or the dual-isotope model (3.6 +/- 0.5 vs. 2.2 +/- 0.2 and 2.7 +/- 0.2 mumol X kg-1 X min-1, respectively, P less than 0.05). During exogenous infusion of unlabeled sodium acetoacetate, the dual-isotope model provided the best estimate of ketone body inflow, whereas 14C specific activity underestimated the known rate of acetoacetate infusion by 55% (P less than 0.02). During sodium beta-hydroxybutyrate infusion, [13C]-acetoacetate overestimated ketone body inflow by 55% (P = NS), while better results were obtained with 14C beta-hydroxybutyrate alone and the two-pool model. Ketone body interconversion as estimated by the dual-isotope technique increased markedly during exogenous ketone body infusion. In conclusion, significant errors in estimation of ketone body inflow were made using single-isotope techniques, whereas a dual-isotope model provided reasonably accurate estimates of ketone body inflow during infusion of exogenous acetoacetate and beta-hydroxybutyrate.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗