Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Acetoacetates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 559 records · Page 31Linked to original sources
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↗
PubMed1984

Ketone body synthesis from leucine by adipose tissue from different sites in the rat.

Leucine is catabolized to ketone bodies in adipose tissue, but the contribution of this output to overall ketone metabolism is not known. The intent of the present study was to determine the capacity of different adipose tissues to synthesize ketone bodies from leucine. The amino acid was readily converted into acetoacetate in epididymal, perirenal, and omental fat tissues. In rats fed ad libitum, the rate of acetoacetate synthesis in omental fat (about 2 mumol g tissue-1h-1) was at least 8 times higher than in epididymal or perirenal fat. In omental fat, the rates of acetoacetate formation from alpha-ketoisocaproic acid were 47-55% lower than from leucine at all concentrations examined. There was no significant synthesis of beta-hydroxybutyrate from leucine or alpha-ketoisocaproic acid. After oxidative decarboxylation, a greater proportion (about three-fourths) of leucine in omental fat was metabolized to acetoacetate than to CO2 production through the Krebs cycle. Although addition of glucose, pyruvate, or carnitine did not affect the production of acetoacetate, fasting for 24 h stimulated acetoacetate synthesis from leucine and alpha-ketoisocaproic acid in omental fat. The high rate of leucine conversion to acetoacetate in omental fat was related to high activities of leucine aminotransferase and branched-chain alpha-keto acid dehydrogenase. Moreover, protein content and cytochrome c oxidase activity of omental mitochondria were, respectively, 13 and 12 times higher than in epididymal mitochondria. In contrast, fat content of epididymal adipose tissue was 21 times that of omental adipose tissue. Epididymal depot consisted of 2.0% protein and 75.8% fat, whereas omental depot contains 17.2% protein and 3.6% fat, resembling that of liver and muscle. The results suggest that the high ketogenic capacity of omental fat stems in part from an augmented mitochondrial mass and high activity of branched-chain alpha-keto acid dehydrogenase.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1971

Evidence for an effect of inulin on the peripheral utilization of ketone bodies in dogs.

The rates of transport and oxidation of acetoacetate have been measured in seven anesthetized, pancreatectomized, ketotic dogs using a constant infusion of acetoacetate-3-(14)C. Control experiments were performed in 14 normal dogs. In addition to the acetoacetate-(14)C, the latter were infused at a constant rate with varying amounts of unlabeled acetoacetate so as to obtain a range of ketone transport (26-65 mumoles/min.kg) comparable with that observed in the diabetic dogs (21-41 mumoles/min.kg). The specific activities of acetoacetate and beta-hydroxybutyrate in blood became equal during the infusion of labeled acetoacetate, indicating that the net transport of acetoacetate represents that of total ketones. In each group, the concentration of ketones was an exponential function of the rate of transport, but for any value below 30 mumoles/min.kg, ketone concentration in the diabetic dogs was about 3 times that in normal dogs, indicating an impairment of mechanisms for utilizing ketones in insulin deficient animals. Maximal capacity to utilize ketones in diabetic dogs was slightly more than half that of normal ones. A similar fraction (32-63%) of the infused (14)C appeared in respiratory CO(2) in the two groups and was independent of the rate of transport. In seven of the normal dogs, administration of insulin and glucose increased removal of the infused ketones and increased the fraction of (14)C appearing in respiratory CO(2). These results demonstrate that utilization of ketones in extrahepatic tissues is influenced by insulin; impaired utilization contributes to diabetic ketosis and is probably essential to the production of severe ketoacidosis.

Acetoacetates↗
PubMed2001

Stability of ketone bodies in serum in dependence on storage time and storage temperature.

The serum concentrations of beta-hydroxybutyrate and acetoacetate as well as the beta-hydroxybutyrate/acetoacetate ratio are important parameters for the differential diagnosis of certain inborn errors of metabolism. Acetoacetate, however, is an unstable compound which becomes rapidly decarboxylated. At a storage temperature of -20 degrees C about 40% of the acetoacetate is lost within 7 days and after 40 days storage at this temperature virtually all of the acetoacetate has become degraded. At -80 degrees C the decomposition of acetoacetate occurs with a much slower rate and only 15% of the initial acetoacetate is lost after 40 days storage. The rate constants for the decarboxylation reaction were found to be (6.4 +/- 2.9) * 10(-5) [min(-1)] at -20 degrees C and (0.4 +/- 0.3) * 10(-5) [min(-1)] at -80 degrees C. In contrast, beta-hydroxybutyrate is very stable during storage and hence should be used as main parameter for the evaluation of ketonemia. If determination of acetoacetate and/or of the beta-hydroxybutyrate/acetoacetate ratio is necessary, an assay immediately after collecting the serum samples is recommended. Otherwise, the serum samples should be frozen as soon as possible and stored at -80 degrees C during transport and storage.

3-Hydroxybutyric Acid↗
PubMed1987

Compartmentation of 14CO2 in the perfused rat liver.

The specific activity of the mitochondrial CO2 + bicarbonate system has been measured in perfused livers using the specific activities of urea and acetoacetate derived from 2-ketoisocaproate catabolism. Label was supplied either as NaH14CO3, 2-keto[1-14C]isocaproate, [1-14C]pyruvate, [1-14C]glutamine, or [14C]formate. With labeled bicarbonate, pyruvate, or 2-ketoisocaproate, the specific activities of effluent bicarbonate, urea, and acetoacetate were equal (acetoacetate was labeled only on C-1). In the presence of [14C]formate, the specific activity of acetoacetate was double that of urea. Acetazolamide (0.2 mM), an inhibitor of carbonic anhydrase, decreased the specific activities of urea and acetoacetate labeled from NaH14CO3 and increased the specific activities of urea and acetoacetate labeled from the other tracers. We conclude that: acetoacetate derived from 2-ketoisocaproate is, like urea, an index of the specific activity of mitochondrial CO2 in liver, carbonic anhydrase activity equalizes the specific activities of the CO2 + bicarbonate system on both sides of the mitochondrial membrane, and a fraction of [14C] formate-derived 14CO2 appears to be generated in a mitochondrial compartment, in the close vicinity of methylcrotonyl-CoA carboxylase.

Acetazolamide↗
PubMed1994

The effects of chronic diabetes and physiological insulin concentration on ketone bodies metabolism in the heart.

In this study the effects of filter-type (Millipore and Whatman No. 54), albumin and insulin at physiological and non-physiological concentrations (12000, 1200, 600, 480, and 300 pM) on D-3-hydroxybutyrate (D-3-HB) utilization and oxidation and acetoacetate production by the isolated nonworking perfused heart from normal and diabetic (4-week) rats was investigated. The use of Whatman No. 54 paper filter to filter the perfusate, in contrast to Millipore filter (0.4 mm) porisity, resulted in the elevation of the rates of utilization and oxidation of D-3-HB and had no effect on acetoacetate production in hearts from normal or diabetic (4-week) rats. Albumin inhibited the utilization and oxidation of D-3-HB, suppressed the percentage of D-3-HB oxidation, increased the percentage of acetoacetate production and had no effect on acetoacetate production in hearts from normal or diabetic rats. Regardless of the filter type and the presence or absence of albumin, the utilization and oxidation of D-3-HB are inhibited and no effect on acetoacetate production was observed in hearts from diabetic rats. Insulin at physiological and non-physiological concentrations in the presence of albumin affects the metabolism of D-3-HB; the stimulations of D-3-HB utilization averaged 32% and 46% in hearts from normal and diabetic rats respectively. The stimulation of D-3-HB oxidation averaged 40% and 60% in hearts from normal and diabetic rats respectively. The D-3-HB utilization and oxidation rates were higher in the hearts isolated from normal rats. No effect of insulin on the rate of acetoacetate production in hearts from normal or diabetic rats was observed, with the exception of an insulin concentration of 1200 pM; there was a 54% reduction in hearts from normal rats. Insulin at 12000 pM had no effect on D-3-HB utilization and oxidation and acetoacetate production in hearts from normal or diabetic rats when perfused using Whatman paper filters in the absence of albumin, but it enhanced the utilization and oxidation of D-3-HB when Millipore paper filters were used.

3-Hydroxybutyric Acid↗
PubMed1986

Determination of human ketone body kinetics using stable-isotope labelled tracers.

In order to avoid the use of radioactive tracers for the determination of human ketone body turnover, we have developed a method using a primed-continuous infusion of 13C-labelled acetoacetate or D-beta-hydroxybutyrate. Determination of the mole percent enrichment of blood acetoacetate and D-beta-hydroxybutyrate was performed by gas chromatography/mass spectrometry. In the post-absorptive state, the mean total ketone body appearance rate, determined in four subjects, was 3.74 mumol X kg-1 X min-1 using [3,4-13C2] acetoacetate and 2.76 mumol X kg-1 X min-1 using [3-13C]D-beta-hydroxybutyrate, values in agreement with those reported in studies with 14C-labelled tracers. In order to evaluate the usefulness of the method for determination of ketone body kinetics in non steady-state conditions, we infused four subjects with natural sodium acetoacetate and calculated the isotopically determined total ketone body appearance rate using a single compartment model (volume of distribution 0.20 l/kg; functional pool fraction: 1). During the tests with [3,4-13C2]-acetoacetate, the actual infusion rates of natural acetoacetate were 7.3 +/- 0.3, 14.6 +/- 0.8, 21.9 +/- 1.2 and 10.9 +/- 0.6 mumol X kg-1 X min-1 whereas the corresponding isotopically determined total ketone body appearance rates were respectively 9.2 +/- 1.0, 16.3 +/- 0.7, 23.1 +/- 1.1 and 10.7 +/- 0.8 mumol X kg-1 X min-1. During the tests with [3-13C]D-beta-hydroxybutyrate, the actual infusion rates were 8.4 +/- 0.5, 16.8 +/- 0.9, 25.2 +/- 1.4 and 12.6 +/- 0.8 mumol X kg-1 X min-1, and the isotopically determined appearance rates respectively 11.1 +/- 0.7, 16.7 +/- 0.7, 25.0 +/- 1.1 and 11.1 +/- 0.7 mumol X kg-1 X min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMedDate not supplied

On the inability of ketone bodies to serve as the only energy providing substrate for rat heart at physiological work load.

The aim of this work was to establish the reasons why ketone bodies, although readily oxidized, do not sustain a physiological work output of the isolated rat heart for more than 30 to 45 min (Taegtmeyer, H., et al., Biochem. J. 186, 701-711 (1980)). First, it was found that the addition of glucose or of asparagine increased the rate of acetoacetate removal by 52 and 77% respectively, and availability of oxaloacetate was one factor limiting the oxidation of acetoacetate. Second, in freeze clamped hearts perfusion with acetoacetate alone caused an increase in the tissue content of acetyl-CoA, citrate, 2-oxoglutarate and glutamate but no change in malate and a decrease in aspartate when compared with glucose as substrate. The changes of aspartate and glutamate exceeded those of 2-oxoglutarate forty times. This means that oxaloacetate formed from aspartate must have passed through the stages of the citric acid cycle to form glutamate and that there was an inhibition of the 2-oxoglutarate dehydrogenase reaction. Third, in hearts perfused with acetoacetate and propionate the accumulation of glutamate and 2-oxoglutarate as well as the decrease in aspartate were associated with a sharp drop in CoASH from 0.258 to 0.093 mumol/g dry wt. This indicates that the accumulation of CoA thioesters left insufficient mitochondrial CoASH for the 2-oxoglutarate dehydrogenase reaction. Fourth, in contrast to acetoacetate cardiac function was unimpaired with acetate plus glucose. With these substrates citrate, 2-oxoglutarate, malate and aspartate all accumulated, either due to formation of oxaloacetate by pyruvate carboxylase or transamination of glutamate with pyruvate. It appears that the changes in cardiac performance and metabolism caused by acetoacetate can be explained by a relative inhibition of the citric acid cycle at the level of 2-oxoglutarate dehydrogenase. The hypothesis is advanced that this might be due to a shortage of intramitochondrial free [CoASH], but the exact mechanism of this inhibition awaits further elucidation.

Acetoacetates↗
PubMed1997

Energy state in HT-29 cells is linked to differentiation.

The relationship between the energy source used by HT-29 cells and their state of differentiation was determined. Short chain fatty acids and acetoacetate were applied to the cells for 9 d, after which the medium was replaced with conventional culture medium for a further 9 d so that the permanence of the changes could be assessed (18 d). Glucose utilization and lactic acid, acetoacetate, and beta-hydroxybutyrate production by the cells were determined. Differentiation was assessed by the presence of the enzymes sucrase-isomaltase and carbonic anhydrase 1, as well as morphological changes of the cells. By tracing carbon from acetate, propionate, and butyrate through the cells, it was found that the carbon from the short-chain fatty acids was fluxed into acetoacetate. Significant amounts of acetoacetate were released by the propionate-treated culture after 9 d and the acetate-, propionate-, valerate-, and caproate-treated cultures after 18 d. A significant positive correlation was found between acetoacetate synthesis and differentiation. Acetoacetate applied to HT-29 cells also induced their differentiation. The acetate-, butyrate-, valerate-, isovalerate-, and caproate-treated cells underwent terminal differentiation, while the propionate- and isocaproate-treated cultures underwent programming events. We, therefore, conclude that HT-29 cells utilize short chain fatty acids in preference to glucose, metabolize these to ketones, thereby raising the energy state and effecting the observed morphological and functional changes in the cells.

Acetoacetates↗
PubMed1989

Formation of ketone bodies by resting lymphocytes.

1. Both beta-hydroxy-beta-methylglutaryl-coenzyme A synthase and lyase activities are present in rat mesenteric lymphocytes: all of the synthase and almost all (80%) of the lyase were present in the mitochondrial compartment of the cell. 2. A high rate of acetoacetate formation was observed in mesenteric lymphocytes incubated in vitro for 60 min in the absence of added substrate; addition of pyruvate or glutamine increased the "endogenous" rate of acetoacetate formation by about 30%. 3. The rates of ketone body formation are similar to maximal rates observed for rat liver. 4. It is suggested that the high rate of endogenous acetoacetate production occurs from long chain fatty acids: this suggestion is consistent with the reported high "endogenous" rate of O2 consumption by lymphocytes. 5. Of the pyruvate metabolized via pyruvate dehydrogenase in lymphocytes, ca 50-70% could be accounted for as acetoacetate, acetate, 3-hydroxybutyrate and citrate: the fate of the remainder is not known. 6. There was a high rate of endogenous acetoacetate formation by isolated mitochondria from these cells. 7. The rate was doubled by addition of pyruvate or butyrate; it was trebled by addition of propionate, ADP or carbonyl cyanide trichloro-methoxyphenylhydrazone; but it was decreased by addition of antimycin A or glutamine. 8. It is suggested that the high rates of acetoacetate formation in these cells acts as a dynamic "buffer" system for the acetyl coenzyme A (CoA) concentration: that is, acetyl CoA is always available for fatty acid synthesis, cholesterologenesis, chain extension of fatty acids or acetylation of proteins (e.g. for covalent control of their activity) which will be demanded at different stages of the cell cycle. 9. This is another example of branch-point sensitivity in control in cells with the potential for rapid cell division.

Acetoacetates↗
PubMed1973

The interconversion and disposal of ketone bodies in untreated and injured post-absorptive rats.

[3-(14)C]Acetoacetate and beta-hydroxy[3-(14)C]butyrate were used to investigate the kinetics of ketone body metabolism in rats 3h after bilateral hind-limb ischaemia and in controls, both groups being in the post-absorptive state and in a 20 degrees C environment. Calculations were carried out as described by Heath & Barton (1973) and the following conclusions were reached. 1. In both injured and control rats, the rates of irreversible disposal (extrahepatic utilization) of beta-hydroxybutyrate and acetoacetate were proportional within experimental error to their blood concentrations up to at least 0.4mm (the maximum found in these rats), implying that they were determined, via these concentrations, by the rates of production by the liver. 2. Conversion of blood beta-hydroxybutyrate into blood acetoacetate took place mainly in the liver, but the reverse process occurred mainly in extrahepatic tissues. 3. The ;metabolic clearance rate' (the volume of blood which, if completely cleared of substrate in unit time, would give a disposal rate equal to that in the whole animal) was calculated for beta-hydroxybutyrate and acetoacetate. Comparison with the cardiac output showed that in control rats the proportion of circulating beta-hydroxybutyrate extracted was lower than that of acetoacetate, clearance of which appeared almost complete. After injury both metabolic clearance rates decreased, probably because of the lower cardiac output. 4. After injury, because the average blood concentrations of ketone bodies, especially acetoacetate, were higher, the mean total rate of disposal also increased. Assuming complete oxidation, the mean contribution of ketone bodies to the whole body O(2) consumption rose from 7 to 15%.

Acetoacetates↗
PubMed1981

Inhibition of bacterial D-3-hydroxybutyrate dehydrogenase by substrates and substrate analogues.

D-3-Hydroxybutyrate dehydrogenase (Pseudomonas lemoignei, EC 1.1.1.30) is subject to substrate inhibition by acetoacetate at concentrations above 5 mM but not by D-3-hydroxybutyrate at concentrations up to 50 mM. NADH causes substrate inhibition at concentrations over 0.1 mM as does NAD. Kinetic analysis suggests that substrate inhibition by acetoacetate is due to its binding to enzyme lacking NADH, a consequence of the ordered bibi mechanism. Substrate inhibition by NADH and NAD arises from binding of these species to a secondary site. This is confirmed by kinetics which indicate that ADP and ATP compete with NAD and NADH at both sites. New analogues of acetoacetate were synthesized to test the specificity requirements of the acetoacetate binding site which has been proposed to contain a hydrogen bond donor and a cation spaced to receive acetoacetate. Both dimethoxyphosphinylacetate and methyl 2-methoxy-phosphinylacetate fulfill the structural requirements and are effective. They thus join methyl acetonylphosphonate as the only known competitive inhibitors for the acetoacetate site, confirming the proposed structure.

Acetoacetates↗
PubMed1992

Etiology of acetonemia in Norwegian cattle. 1. Effect of ketogenic silage, season, energy level, and genetic factors.

Plasma acetoacetate concentration in the 1st mo of lactation and its relation to BW change, milk yield, DMI, and BW postpartum were studied in 361 first lactation cows during 6 yr. The cows were fed concentrate at 6 and 3 kg/d. Calvings took place from August to December. Single observations for all cows were fitted by a multitrait animal model that accounted for all genetic relationships. Heritability for acetoacetate was .11 with a genetic correlation of .87 for milk yield, -.65 for weight change, and -.13 for BW postpartum. Acetoacetate was higher at 3 kg/d of concentrate than at 6 kg/d, and calving after 3 to 4 mo of indoor feeding was related to higher acetoacetate than was calving shortly after the pasture season. Acetoacetate was related to weight loss postpartum, but at a different degree in different years. In some years, compounds of the silage caused strongly elevated plasma concentrations of acetoacetate after feeding. Experiments were performed to compare hay with silages of different qualities. Rumen concentration of different amines 3 h postfeeding was taken as an index of the amine load of the cow. The concentration of several amines in rumen fluid were high after feeding ketogenic silage.

Acetoacetates↗
PubMed1984

Ketone body kinetics in humans: the effects of insulin-dependent diabetes, obesity, and starvation.

The kinetics of acetoacetate (A) and beta-hydroxybutyrate (B) have been studied following the injection as a pulse or continued infusion of [3-14C]acetoacetate (A*) or [14C]beta-hydroxybutyrate (B*) into six newly diagnosed, untreated, ketotic diabetic patients, ten obese subjects in the postabsorptive state, and the ten obese subjects after 1-2 weeks starvation (50 cal per day). Employing a compartmental model of acetoacetate and beta-hydroxybutyrate kinetics developed using CONSAM for normal subjects, the rate coefficients (Lij), rates of release of newly synthesized acetoacetate and beta-hydroxybutyrate into the blood (UA, UB), and fractional removal of each compound (FCRA and FCRB) were calculated. Ketone body release into blood (UA + UB) in diabetic subjects was threefold higher than normal (mean +/- SD, 208 +/- 118 versus 81 +/- 66 mumol min-1 m-2) and in obese subjects the rate increased on starvation from 171 +/- 70 to 569 +/- 286 mumol min-1 m-2. In each case most of the increase was in beta-hydroxybutyrate. The major change in diabetes and on starvation of the obese subjects was in the rate coefficient for removal of ketone bodies. Normally 0.168 +/- 0.109 min-1, it was 0.055 +/- 0.040 min-1 in the diabetic patients and fell from 0.066 +/- 0.040 to 0.027 +/- 0.019 min-1 in the obese subjects on starvation. In normal subjects, FCRA was similar to FCRB (0.226 +/- 0.142 versus 0.188 +/- 0.124 min-1). However, in diabetics, FCRA was 0.074 +/- 0.044 and FCRB was 0.050 +/- 0.034 min-1 and both were lower than normal. On starvation of obese subjects, FCRA fell from 0.199 +/- 0.047 to 0.089 +/- 0.035 min-1, whereas FCRB fell from 0.141 +/- 0.040 to 0.033 +/- 0.012 min-1. Therefore, the removal of beta-hydroxybutyrate was impaired more than that of acetoacetate in all patients. Our results confirm previous observations that ketosis is associated with high rates of ketogenesis and a decrease in fractional clearance. In addition, we found that in diabetes, obesity, and in obese subjects following starvation, most of the increased synthesis was in beta-hydroxybutyrate and that the clearance of beta-hydroxybutyrate decreased more than that of acetoacetate.

3-Hydroxybutyric Acid↗
PubMed1991

Effects of ketones, acetate, butyrate, and glucose on bovine lymphocyte proliferation.

Blood leukocytes from age-matched heifers were used to determine effects of ketones, acetate, butyrate, and glucose on in vitro lymphocyte proliferation. Lymphocytes stimulated with concanavalin A, phytohemagglutinin-P, or pokeweed mitogen were cultured in the presence or absence of beta-hydroxybutyrate, acetoacetate, acetone, acetate, butyrate, and glucose. Only supraphysiological levels of beta-hydroxybutyrate inhibited proliferation in cultures of mitogen-stimulated lymphocytes, whereas mixtures of beta-hydroxybutyrate and acetoacetate at levels seen in severe ketosis stimulated concanavalin A and phytohemagglutinin-P-driven proliferation. Because acetoacetate was a lithium salt, lithium chloride served as a negative control. Results suggest the enhanced proliferation by cultures containing lithium acetoacetate was due to lithium, not acetoacetate. Butyrate (at concentrations greater than seen in bovine plasma) and acetate at normal levels inhibited proliferation. Concanavalin A- and pokeweed-mitogen-driven proliferation was greater in cultures containing lower glucose levels, but acetate added to cultures containing low glucose inhibited concanavalin A-stimulated proliferation. Proliferation by pokeweed mitogen-stimulated cultures containing acetate, beta-hydroxybutyrate, and acetoacetate was suppressed at the lower concentrations of glucose tested. In conclusion, ketones, butyrate, and glucose at concentrations occurring in vivo had minimal effects on bovine lymphocyte proliferation in vitro. Levels of acetate associated with ketosis suppressed lymphocyte function and may alter immune responsiveness in vivo.

Acetates↗
PubMed1990

Enzymes involved in anaerobic degradation of acetone by a denitrifying bacterium.

The pathway of anaerobic acetone degradation by the denitrifying bacterial strain BunN was studied by enzyme measurements in extracts of anaerobic acetone-grown cells. An ADP- and MgCl2-dependent decarboxylation of acetoacetate was detected which could not be found in cell-free extracts of acetate-grown cells. It is concluded that free acetoacetate is formed by ATP-dependent carboxylation of acetone. Acetoacetate was converted into its coenzyme A ester by succinyl-CoA: acetoacetate CoA transferase, and cleaved by a thiolase into acetyl-CoA. The acetyl residue was completely oxidized in the citric acid cycle. The ADP-dependent decarboxylation of acetoacetate was inhibited by EDTA, but not by avidin. High myokinase activities led to equilibrium amounts of ATP, ADP, and AMP in the reaction mixtures, and prevented determination of the decarboxylase reaction stoichiometry, therefore.

Acetoacetates↗
PubMed1985

Impaired ketone body metabolism in the selenium deficient rat. Possible implications.

Male rats were fed a selenium-deficient Torula yeast diet with or without 0.2 ppm selenium (as sodium selenite) in the drinking water. Selenium deficiency caused a significant increase of urinary acetoacetate excretion in fed rats, and 24 or 48 hours of starvation enhanced this effect. Two days of selenium supplementation decreased the amount of urinary acetoacetate and 3-hydroxybutyrate to 50% of the deficiency value, indicating an enzymatic impairment in the selenium-deficient rat. No selenium-dependent effect was found for the following: (1) urinary pH, amount of nitrite, glucose (negative), hemoglobin or protein, and the urine was negative for phenylketones; (2) blood content of glucose, acetoacetate, or 3-hydroxybutyrate; or (3) liver content of glycogen, glucose, acetoacetate, or 3-hydroxybutyrate. On the other hand, the liver content of triglycerides was significantly lower in selenium deficiency. Indications for a higher content of ketone bodies (acetoacetate plus 3-hydroxybutyrate) in the kidneys from selenium-deficient rats were found. The increased urinary excretion of ketone bodies on selenium deficiency may indicate an impairment of lipid and ketone body turnover (in the kidney), or a decreased kidney reabsorption rate. Possible implications of these results in connection with protective roles of selenium in atherosclerosis and carcinogenesis are suggested.

Acetoacetates↗
PubMed1981

Mitochondrial/cytosolic carbon transfer in the developing rat brain.

The rates of citrate and acetoacetate efflux from rat brain mitochondria (synaptic and free) utilizing different substrates (pyruvate, 3-hydroxybutyrate or acetoacetate) under different conditions have been studied as a function of development. In general there were no marked differences in the acetoacetate efflux rates between 'free' and 'synaptic' brain mitochondria whereas citrate efflux rates were usually higher in 'free' mitochondria. Developmental studies with brain mitochondria utilizing 3-hydroxybutyrate + malate showed a profile for acetoacetate efflux which was at a peak at weaning (21 days) and then decreased by 50% in the adult state. Similar studies measuring citrate efflux showed little change as the brain developed, but when pyruvate + malate were used as substrates the citrate efflux doubled during the period 5--20 days and was then maintained in the adult state. Phenylpyruvate was found to inhibit both acetoacetate and citrate efflux from 21-day-old and adult rat brain mitochondria when they used either 3-hydroxybutyrate or pyruvate as substrate. It is concluded that ketone bodies may be potentially as effective, if not better, than glucose in the brain of the suckling rat as precursors of cytosolic biosynthetic activities whereas in the adult rat brain, ketone bodies are relatively poor precursors of these activities.

Acetoacetates↗