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 847 records · Page 47Linked to original sources
PubMed1985

Propionate loading test for liver function in spontaneously ketotic dairy cows.

Propionate utilisation by the liver in spontaneously ketotic dairy cows was investigated by determining blood glucose levels after an intravenous sodium propionate load (2.5 mmol kg-1). In addition, blood ketone body concentrations were measured after propionate loading. Cows were divided into three groups (control, mildly ketotic and severely ketotic) by their blood acetoacetate concentrations. Plasma glucose concentrations increased significantly after sodium propionate injection in all three groups (P less than 0.05). The maximum glucose concentration occurred earlier in the control group than in the ketotic groups. Changes in glucose concentrations following propionate loading of control and ketotic cows differed significantly at 20 minutes and beyond. Differences in the change in glucose concentration between mildly ketotic and severely ketotic cows were not significant. Acetoacetate concentration was significantly decreased at five minutes and beyond after the injection in ketotic cows, whereas beta-hydroxybutyrate concentration decreased more slowly. A decrease in beta-hydroxybutyrate concentration was significant at 40 minutes and beyond in the severely ketotic group and at 10 minutes and beyond in the mildly ketotic group after loading.

3-Hydroxybutyric Acid↗
PubMed1966

Factors influencing the utilization of ketone bodies by mouse adipose tissue.

Factors influencing the utilization of ketone bodies by mouse adipose tissue in vitro were studied. Epididymal fat pads can oxidize DL-Beta-hydroxybutyrate-3-(14)C and acetoacetate-3-(14)C to (14)CO(2) as well as convert these compounds to fatty acid-(14)C. An increased output of (14)CO(2) from Beta-hydroxybutyrate-3-(14)C was noted in response to glucose plus insulin, succinate, oxaloacetate, L-asparate, and L-malate. Fatty acid synthesis from Beta-hydroxybutyrate was enhanced by glucose plus insulin, L-aspartate, L-malate, oxaloacetate, and citrate. Nicotinamide stimulated the oxidation of Beta-hydroxybutyrate but not of acetoacetate to CO(2), and did not affect fatty acid synthesis from either ketone body. Nicotinamide increased NAD(+) and NADP(+) levels in epididymal fat pads without affecting the concentration of NADH and NADPH. "Superlipogenesis" caused by fasting the mice for 48 hr and re-feeding them for 24 hr sharply enhanced CO(2) output and lipogenesis from Beta-hydroxybutyrate. The activities of glucose-6-phosphate dehydrogenase, 6-phosphogluconic dehydrogenase, NADP-malic dehydrogenase, and citrate cleavage enzyme from mouse adipose tissue were increased during "superlipogenesis." Free fatty acid release by epididymal fat pads in vitro was slightly increased by Beta-hydroxybutyrate. The relationship of ketone body metabolism and lipogenesis in adipose tissue is discussed.

Acetoacetates↗
PubMed1982

Interrelationships between hydrogen-supplying reactions, respiration rate and extramitochondrial adenine nucleotide pattern.

1. The influence of a diminished hydrogen supply on the regulation of oxidative phosphorylation of isolated rat liver mitochondria in dependence on the extramitochondrial (ATP)/(ADP) ratio was investigated. 2. The hydrogen supply was diminished by using various (beta-hydroxybutyrate)/(acetoacetate) ratios as a redox buffer and the results were compared with those of experiments using perifusion of immobilized mitochondria with non-saturating substrate concentrations. 3. In both experimental approaches the influence of a diminished hydrogen pressure on the maximum (ATP)/(ADP) ratio at minimum flux was low. An extreme decrease in the (beta-hydroxybutyrate)/(acetoacetate) ratio by more than two orders of magnetitude causes the (APT)/(ADP) ratio to decrease by about 50%. 4. The load capacity of oxidative phosphorylation (maximum flux) is considerably decreased by diminished hydrogen pressure. 5. The borderline cases of purely kinetic and thermodynamic limitations of hydrogen supply were calculated by computer simulation with respect to the regulating behaviour of oxidative phosphorylation and changes in the control strength of adenine nucleotide translocator and hydrogen supply in the overall reaction. 6. A prevalent thermodynamic influence of hydrogen supply on oxidative energy transformation in the cell is discussed in the light of experimental data.

3-Hydroxybutyric Acid↗
PubMed1984

Evidence for possible interrelationship between gluconeogenesis and ketogenesis?

Effects of ketogenic substrates on gluconeogenesis by rat hepatocytes were examined. D,L-3-Hydroxybutyrate (5 mM) stimulated gluconeogesis from lactate by 41%, the effect being the same as that of 5 mM acetate (43%). Acetoacetate up to 40 mM had no stimulating effect; conversely, it partially or completely abolished the observed stimulating effects of acetate, 3-hydroxybutyrate, or oleate. 3-Hydroxybutyrate also stimulated gluconeogenesis from serine by 70%, the effect being much higher than that of acetate (35%). No effect of 3-hydroxybutyrate or acetate on gluconeogenesis from pyruvate was seen. It is proposed that, in intact liver cells, pyruvate is transported into mitochondria in exchange for intramitochondrially generated acetoacetate, and that the mechanism proposed may be of physiological importance.

3-Hydroxybutyric Acid↗
PubMed1994

Arterial ketone body ratio in liver surgery.

To evaluate the relevance of the hypothesis that the arterial ketone body ratio (acetoacetate/beta-hydroxybutyrate) can reflect the liver mitochondrial redox potential, we investigated the influence of ketone body metabolism in peripheral tissues on the arterial ketone body ratio during conditions in which no ketone body was available to the systemic circulation: during total clamping of the hepatoduodenal ligament in 37 patients undergoing partial hepatectomy and during the anhepatic phase in 14 liver transplant recipients. Changes in both the arterial acetoacetate and beta-hydroxybutyrate concentrations and arterial ketone body ratio varied markedly from patient to patient after clamping. Among 20 patients with hepatocellular carcinoma and associated chronic liver disease, arterial ketone body ratio 15 min after clamping was higher in 11 and lower in 9 than that before clamping. Of the remaining 17 patients with other types of tumor, arterial ketone body ratio was increased in 10 and decreased in 7 after clamping. Similar changes were observed in 14 recipients during the anhepatic phase of liver transplantation. Arterial ketone body ratio was increased in 7 recipients during the anhepatic phase compared with that at laparotomy, whereas it was lowered in the remaining 7. These results indicate that each of the two types of ketone body is metabolized in extrahepatic tissues to a different extent, varying among individual patients and disease conditions. We conclude that arterial ketone body ratio does not solely reflect the ratio of the amounts of acetoacetate to beta-hydroxybutyrate produced by the liver. This may make it difficult to use arterial ketone body ratio as an accurate parameter representing the redox state in liver mitochondria.

3-Hydroxybutyric Acid↗
PubMed1993

The effect of contraceptive steroids on hepatic cholesterol metabolism in female rats (I).

In order to determine effects of contraceptive steroids with respect to dose, progestin type and duration of administration, on hepatic cholesterol metabolism, rats were treated with two different (ethinyl estradiol/norethisterone acetate and ethinyl estradiol/levonorgestrel) combinations orally at two different-low and high-doses and- short and long-terms. At the end of the experiments, total cholesterol and acetoacetate levels in plasma samples and HMG-CoA synthase and AcAc-CoA thiolase activities in the livers of rats were measured. In all groups, acetoacetate was found to be higher than in controls, and except in low dose- ethinyl estradiol/levonorgestrel treated groups, total cholesterol was also increased. In the short period treatments HMG-CoA synthase and AcAc-CoA thiolase (except in low dose-ethinyl estradiol/levonorgestrel group) activities were increased. But enzyme activities were either decreased or not changed in long period treatments. It is suggested that increased enzyme activities in short period treatments may increase total cholesterol levels, and that in time, these levels may lead to a suppression of enzyme activities.

Acetoacetates↗
PubMed1993

A study of interferences in routine methods for creatinine measurement.

A survey was undertaken through the Irish External Quality Assessment Scheme to investigate the extent to which acetoacetate and bilirubin affect routine methods in current use for measurement of serum creatinine. Spiking a sample with 10 mmol/l acetoacetate caused errors ranging from -28% to +22%. The greatest errors were found with end-point Jaffé methods and kinetic Jaffé methods in which there was no time delay between final reagent addition and start of absorbance measurement. A sample with high bilirubin concentration gave apparent creatinine results ranging from zero to 280 mumol/l. Although these interferences are well documented in the literature, this knowledge seems to have had little effect on methods in actual use.

Acetoacetates↗
PubMed1976

Effect of experimentally induced hyperketonemia on glucose metabolism of ovine brain in vivo.

The effect of high concentrations of circulating acetoacetate on the uptake and utilization of glucose-U-14C was investigated in brain of fed and 7-day fasted sheep. Uniformly 14C-labeled glucose and nonlabeled acetoacetate were infused via the jugular vein while blood samples were being taken from the carotid artery and dorsal sagittal sinus. Samples were analyzed for CO2 and its specific activity, glucose and its specific activity, ketone bodies, lactic acid, plasma-free fatty acids, and plasma-immunoreactive insulin. During 1 hour of infusion of 5 mM of acetoacetate/kg/hour, there was a significant decrease (P less than 0.05) in blood glucose concentration and a significant (P less than 0.05) decrease in the uptake of glucose by the brain. Significant (P less than 0.001) arteriovenous differences across the brain in ketone body concentration were observed in both fed and fasted sheep. Also, a significant increase in plasma-immunoreactive insulin and lactate and a decrease in plasma-free fatty acids were observed. These results indicate that hyperketonemia induced hypoglycemia and reduced the uptake of glucose. It also increased the uptake of ketone bodies and increased lactate production by the ovine brain.

Acetoacetates↗
PubMed1999

Synthesis, calcium channel antagonist activity, and anticonvulsant activity of 3-ethyl 5-methyl 1,4-dihydro-2-[(2-hydroxyethoxy) methyl]-6-methyl-4-(2,3-dichlorophenyl)-3,5-pyridinedicarboxylate coupled to a 1-methyl-1,4-dihydropyridyl-3-carbonyl chemical delivery system.

3-Ethyl 5-methyl 1,4-dihydro-2-[(2-hydroxyethoxy) methyl]-6-methyl-4-(2,3-dichlorophenyl)-3,5-pyridinedicarboxylate (13), a bioisostere of amlodipine, was prepared by the reaction of ethyl 4-(2-hydroxyethoxy)acetoacetate (11) with methyl 2-(2,3-dichlorobenzylidene)acetoacetate (12) and NH4OAc. Compound 13 was elaborated to the target product 3-ethyl 5-methyl 1,4-dihydro-2-[2- [(1-methyl-1,4-dihydropyridyl-3-carbonyloxy)ethoxy]methyl]- 6-methyl-4-(2,3-dichlorophenyl)-3,5-pyridinedicarboxylate (16). The C-2 CH2OCH2CH2OH compound (13, IC50 = 6.56 x 10(-9) M) was about 44-fold more active as a calcium channel antagonist than the reference drug nimodipine (IC50 = 1.49 x 10(-8) M), but 4-fold less potent than felodipine (IC50 = 1.45 x 10(-9) M). Compound 16, possessing the 1-methyl-3-pyridylcarbonyloxy chemical delivery system moiety is a slightly less potent calcium channel antagonist (IC50 = 2.99 x 10(-8) M) than the parent compound 13. Compounds 13, 16, felodipine and nimodipine are highly lipophilic (Kp = 227, 344, 442 and 187, respectively). The C-2 CH2OCH2CH2OH compound (13) exhibited equipotent anticonvulsant activity to nimodipine in the maximal electroshock (MES) anticonvulsant screen. Unlike nimodipine, 13 provided modest protection in the subcutaneous metrazol (scMet) anticonvulsant screen. In contrast, compound 16 was inactive in both the MES and scMet screens.

Animals↗
PubMed2002

Changes in protein synthesis and identification of proteins specifically induced during solventogenesis in Clostridium acetobutylicum.

At the end of the exponential growth phase the Gram-positive bacterium Clostridium acetobutylicum performs a metabolic switch from classical sugar fermentation accompanied by the production of acetate and butyrate to reinternalization and oxidation of these acids to acetone and butanol. Protein synthesis in acidogenic and solventogenic C. acetobutylicum cells was compared by two-dimensional gel electrophoresis of radioactively labeled proteins. The results show that the switch from acid to solvent production is accompanied by dramatic changes in the protein pattern. During solventogenesis, the synthesis of 52 proteins out of 130 analyzed was increased more than twofold, the synthesis of 34 proteins decreased to less than half as compared with synthesis in acidogenic cells. The changes in protein synthesis were generally reflected by changes in the abundance of the respective proteins, as determined from quantitative analysis of silver-stained second-dimensional gels. Nine proteins induced during solventogenesis were identified by N-terminal microsequencing. One of these proteins, the acetoacetate decarboxylase, is directly involved in solventogenesis. Other proteins synthesized in higher amounts during solventogenesis were three general stress proteins (DnaK, GroEL, Hsp 18), two enzymes involved in serine biosynthesis (serine aminotransferase and 3-phosphoglycerate dehydrogenase) as well as a seryl-tRNA synthetase. mRNA analysis provided evidence that the latter three are encoded by genes organized in an operon and are transcriptionally induced at the onset of solventogenesis. The proteins acetoacetate decarboxylase and Hsp 18 occurred in two variants, indicating possible covalent modification of these proteins.

Acetic Acid↗
PubMedDate not supplied

Comparative acute effects of leptin and insulin on gluconeogenesis and ketogenesis in perfused rat liver.

The acute effects of physiological levels of leptin (10 ng ml(-1)) and insulin (20 microU ml(-1)) on hepatic gluconeogenesis and ketogenesis were compared. Leptin or insulin alone decreased (p<0.05) the activation of hepatic glucose, L-lactate and urea production from L-alanine. However, the hepatic glucose production was not modified if leptin was combined with insulin. These results indicated that both, i.e. leptin and insulin, could promote a non-additive reduction in the rate of catabolism of L-alanine. However, in contrast with insulin (p<0.05), leptin did not inhibit the activation of hepatic glucose production from pyruvate or glycerol. On the other hand, activation of hepatic production of acetoacetate and beta-hydroxybutyrate from octanoate was not affected by leptin or insulin. Thus, our data demonstrate that the acute effect of leptin on hepatic metabolism was partially similar to insulin (activation of glucose production from L-alanine and activation of acetoacetate or beta-hydroxybutyrate production from octanoate) and partially different from insulin (activation of glucose production from pyruvate or glycerol).

Alanine↗
PubMed1991

Plasma levels of glucose, ketone bodies, lactate, and alanine in the vascular supply to and from the brain of the adult American bullfrog (Rana catesbeiana).

Serial, paired blood samples were collected via cannulae chronically placed in the common carotid artery (A) to and the internal jugular vein (V) from the brain of the fasted adult American bullfrog (Rana catesbeiana). Plasma glucose, beta-hydroxybutyrate, acetoacetate, lactate, and alanine levels were measured by standard enzymatic procedures. Cannula failure ended sampling after 1-2 days in most animals. The common carotid artery plasma metabolite levels were greatest at the time of surgery and subsequently declined to relatively stable levels. The summarized data indicated glucose uptake and alanine release by the brain, but no significant beta-hydroxybutyrate or lactate A-V percentage changes. Initially, acetoacetate levels also were measured, but were discontinued in favor of continued beta-hydroxybutyrate determinations when no significant A-V percentage changes occurred. Separate analysis of the metabolite levels during the surgery and recovery period (less than or equal to 24 hr) and the "normal" under the experimental conditions period (greater than 24 hr) revealed that summarizing the data masked important A-V percentage changes during the two different physiological conditions. Glucose was the only metabolite extracted by the brain during the less than or equal to 24 hr period of elevated and subsequently declining metabolite levels. In contrast, glucose uptake did not occur during the greater than 24 hr period of stable levels, but there was lactate release. If the bullfrog brain stores substantial glycogen as do the other ectothermic vertebrates studied, glucose uptake when plasma levels are elevated, for example after feeding, may serve both to fuel the brain and to replenish endogenous glycogen reserves that may be mobilized to provide glucose for the brain after plasma glucose levels return to normal. Assuming that mammalian and bullfrog metabolic pathways are the same, the release of lactate and alanine by the brain, possibly to remove excess pyruvate and to regenerate NAD+, is consistent with this hypothesis. It remains to be determined for how long endogenous energy sources alone can support the bullfrog brain, and if plasma glucose, ketones, and/or other energy sources are extracted as endogenous brain fuels become exhausted.

Alanine↗
PubMed2001

Strategies for neuroprotection against L-trans-2,4-pyrrolidine dicarboxylate-induced neuronal damage during energy impairment in vitro.

Increased levels of extracellular excitatory amino acids and failure of energy metabolism are two conditions associated with brain ischemia. In the present study we have combined the simultaneous inhibition of glutamate uptake and mitochondrial electron transport chain to simulate neuronal damage associated with brain ischemia. Results show that cerebellar granule neurons are not vulnerable to transient glutamate uptake inhibition by L-trans-pyrrolidine-2,4-dicarboxylate (PDC) despite the increase in the extracellular concentration of glutamate, unless they are simultaneously exposed to the mitochondrial toxins 3-nitropropionic acid (3-NP) or sodium azide. Cell damage was assessed by light microscopy observation, by reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and by the fluorescent markers for live and dead cells, calcein and ethidium homodimer, respectively. The protective effect of alternative energy substrates, such as pyruvate, acetoacetate, and beta-hydroxybutyrate against PDC-induced neuronal death during 3-NP exposure was studied and compared to the effects of the antioxidant vitamin E, the spin trapper alpha-phenyl-N-tert-butylnitrone (PBN), voltage-dependent calcium channel antagonists, and glutamate receptor antagonists. Results show that neuronal damage can be efficiently prevented in the presence of pyruvate and the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801, whereas the non-NMDA receptor antagonist NBQX, acetoacetate, vitamin E, and PBN showed partial protection. In contrast, beta-hydroxybutyrate and voltage-dependent calcium channels blockers did not show any protective effect at the concentrations tested.

Animals↗
PubMed1989

Effects of human diabetic serum on the in vitro development of early somite rat embryos.

High levels of glucose, beta-hydroxybutyrate (B-HOB), and acetoacetate are known to have embryotoxic and teratogenic effects on rat embryos in culture, especially when added concomitantly to the culture medium. We studied the effects of human serum from different types of diabetes mellitus on the in vitro development of 10 1/2-day-old rat embryos cultured for 48 hours. We used serum from type I diabetes with and without ketoacidosis and type II diabetes either untreated or treated with insulin or with daonil. Type I diabetes without ketoacidosis increased the rate of malformations to 27% vs. 11% in controls. Serum from type I diabetes with ketoacidosis further increased the malformation rate to 44%. The rate of malformations induced by serum of type II diabetes was dependent on the treatment. It was relatively low among embryos cultured on serum from untreated (16%) or treated with daonil (19%) and rose to 27% among embryos cultured on serum from type II diabetes treated with insulin. No significant correlation was found between the rate of malformations and the concentrations of glucose, B-HOB, acetoacetate, and HbA1c in all diabetic sera except serum from type I diabetes with ketoacidosis. We may therefore conclude that for most types of diabetes in humans, neither the high blood glucose concentrations nor the high levels of ketone bodies seem to be the main reason for the high rate of malformations. However, we used cultured rat embryos, and the effects on the human embryo may be different. The results of studies on various experimental animal models in diabetes teratogenicity seem to have only partial relevance to the human situation.

Animals↗
PubMed1997

Influence of the redox state of pyridine nucleotides on mitochondrial sulfhydryl groups and permeability transition.

This work addresses a correlation between the redox state of pyridine nucleotides and that of sulfhydryl groups of the mitochondrial membranes. Several major observations emerge: (1) Conditions leading to an oxidation of the pyridine nucleotides such as incubation with tert-butyl hydroperoxide or acetoacetate determine a decrease of total mitochondrial sulfhydryl groups. Glutathione does not follow the same pattern since it decreases in the presence of tert-butyl hydroperoxide but not in the presence of acetoacetate. In addition, only in the presence of tert-butyl hydroperoxide is the decrease of sulfhydryl groups concomitant with a membrane protein polymerization, observed by polyacrylamide gel electrophoresis. (2) Under all conditions tested, the oxidation of sulfhydryl groups is further stimulated by the presence of calcium and phosphate ions. (3) Respiratory substrates, which prevent the swelling of mitochondria, also partially prevent the decrease of sulfhydryl groups.

Animals↗
PubMed1995

A chemiluminescence-flow injection analysis of serum 3-hydroxybutyrate using a bioreactor consisting of 3-hydroxybutyrate dehydrogenase and NADH oxidase.

We describe a simple method for the highly sensitive chemiluminescence--flow injection analysis of 3-hydroxybutyrate in serum using a bioreactor column consisting of the two immobilized enzymes, 3-hydroxybutyrate dehydrogenase and NADH oxidase. The method was based on measuring the level of chemiluminescence formed by the reaction of a luminol-hexacyanoferrate mixture with hydrogen peroxide. The hydrogen peroxide was produced by the NADH oxidase reaction from NADH which was formed in the conversion of 3-hydroxybutyrate to acetoacetate by the 3-hydroxybutyrate dehydrogenase reaction. Among three immobilized enzyme columns, a coimmobilized, small 3-hydroxybutyrate dehydrogenase/NADH oxidase bioreactor alone (2 x 20 mm i.d.) readily hydrolyzed all of the injected 3-hydroxybutyrate into acetoacetate, although 3-hydroxybutyrate dehydrogenase catalyzed the reversible reaction. The present method generated linearity of the data up to 1.5 mM 3-hydroxybutyrate with satisfactory precision, reproducibility, and accurate reaction recoveries. The results from 3-hydroxybutyrate correlated satisfactorily with those obtained by other well-established methods. The coimmobilized 3-hydroxybutyrate dehydrogenase/NADH oxidase reactor unit showed good operational stability over a 5-week period, during which it was repeatedly used for 1500 analyses.

3-Hydroxybutyric Acid↗
PubMed1983

The 75-g oral glucose tolerance test: effect on splanchnic metabolism of substrates and pancreatic hormone release in healthy man.

To determine the effect of the 75 g oral glucose tolerance test on carbohydrate and lipid metabolism, the splanchnic exchange of glucose, lactate, pyruvate, non-esterified fatty acids, beta-hydroxybutyrate and acetoacetate as well as the release of insulin, C-peptide, glucagon and pancreatic polypeptide were evaluated in eight healthy male volunteers in the basal state and for 150 min following glucose ingestion. Oral glucose loading was followed by a rapid rise in splanchnic output of glucose (mean +/- SEM; 154 +/- 12 mmol/150 min), pyruvate (1.2 +/- 1.2 mmol/150 min) and lactate (8.6 +/- 2.0 mmol/150 min), whereas there were reductions in the splanchnic uptake of non-esterified fatty acids (-10.7 +/- 4.4 mmol/150 min) and the splanchnic output of beta-hydroxybutyrate (-4.8 +/- 3.3 mmol/150 min) and acetoacetate (-3.0 +/- 1.2 mmol/150 min). In parallel, splanchnic output of insulin (12.3 +/- 2.7 nmol/150 min), C-peptide (36.1 +/- 5.0 nmol/150 min) and transiently of pancreatic polypeptide rose, whereas that of glucagon fell (-0.58 +/- 0.21 nmol/150 min). Even at 150 min after glucose ingestion, splanchnic output and arterial concentrations of glucose, lactate, insulin and C-peptide were still above their respective basal values while those of non-esterified fatty acids and glucagon were reduced. Taking into account the partial suppression of endogenous glucose production by ingested glucose it is concluded that, in normal postabsortive man, only 49-63% of a 75 g oral glucose load is retained by the splanchnic bed during the first 150 min, the rest being available for non-hepatic tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Metabolic pathways and energetics of the acetone-oxidizing, sulfate-reducing bacterium, Desulfobacterium cetonicum.

Acetone degradation by cell suspensions of Desulfobacterium cetonicum was CO2-dependent, indicating initiation by a carboxylation reaction. Degradation of butyrate was not CO2-dependent, and acetate accumulated at a ratio of 1 mol acetate per mol butyrate degraded. In cultures grown on acetone, no CoA transfer apparently occurred, and no acetate accumulated in the medium. No CoA-ligase activities were detected in cell-free crude extracts. This suggested that the carboxylation of acetone to acetoacetate, and its activation to acetoacetyl-CoA may occur without the formation of free acetoacetate. Acetoacetyl-CoA was thiolytically cleaved to two acetyl-CoA, which were oxidized to CO2 via the acetyl-CoA/carbon monoxide dehydrogenase pathway. The measured intracellular acyl-CoA ester concentrations allowed the calculation of the free energy changes involved in the conversion of acetone to acetyl-CoA. At in vivo concentrations of reactants and products, the initial steps (carboxylation and activation) must be energy-driven, either by direct coupling to ATP, or coupling to transmembrane gradients. The delta G' of acetone conversion to two acetyl-CoA at the expense of the energetic equivalent of one ATP was calculated to lie very close to 0 kJ (mol acetone)-1. Assimilatory metabolism was by an incomplete citric acid cycle, lacking an activity oxidatively decarboxylating 2-oxoglutarate. The low specific activities of this cycle suggested its probable function in anabolic metabolism. Succinate and glyoxylate were formed from isocitrate by isocitrate lyase. Glyoxylate thus formed was condensed with acetyl-CoA to form malate, functioning as an anaplerotic sequence. A glyoxylate cycle thus operates in this strictly anaerobic bacterium. Phosphoenolpyruvate (PEP) carboxykinase formed PEP from oxaloacetate.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetone↗