Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Hydroxybutyrates”

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 181 records · Page 10Linked to original sources
PubMed1988

Ketone-body metabolism in hyperthyroid rats: reduced activity of D-3-hydroxybutyrate dehydrogenase in both liver and heart and of succinyl-coenzyme A: 3-oxoacid coenzyme A-transferase in heart.

The specific activity of D-3-hydroxybutyrate dehydrogenase is reduced by about a third in liver and heart mitochondria of hyperthyroid rats. State 3 respiration is also reduced in isolated mitochondria from the same animals when DL-3-hydroxybutyrate is the substrate. Determination of the kinetic parameters of the membrane-bound D-3-hydroxybutyrate dehydrogenase in liver of hyperthyroid rats reveals a decreased in maximal velocity (Vmax). The Michaelis and dissociation constants of NAD+ and D-3-hydroxybutyrate are also significantly influenced, thus indicating that both the affinity and the binding of this enzyme toward its substrates are affected. In hyperthyroid rats a significant ketone-body increase is found in both liver and heart: in blood, an almost doubled concentration can be measured. At the same time, in heart mitochondria of these animals the activity of succinyl-coenzyme A: 3-oxoacid coenzyme A-transferase is significantly reduced. The decrease in both D-3-hydroxybutyrate dehydrogenase and 3-oxoacid coenzyme A-transferase associated with the increase in ketone bodies supports the suggestion that there is a lower utilization of these compounds by peripheral tissues. In the blood of hyperthyroid rats a higher D-3-hydroxybutyrate/acteoacetate ratio is also found, probably resulting from a selective utilization of the two compounds in this pathological state.

Acyl Coenzyme A↗
PubMed1978

Effects of pH on beta-hydroxybutyrate transport in rat erythrocytes and thymocytes.

Entry of beta-hydroxybutyrate into erythrocytes and thymocytes is facilitated by a carrier (C), as judged from temperature dependence, saturation kinetics, stereospecificity, competition with lactate and pyruvate, and inhibition by moderate concentrations of methylisobutylxanthine, phloretin, or alpha-cyanocinnamate. We studied the dependence of influx and efflux on internal and external pH and [beta-hydroxybutyrate]. Lowering external pH from 8.0 to 7.3 to 6.6 enhanced influx into erythrocytes by lowering entry Km from 29 to 16 to 10 mM, entry V being independent of external pH. Lowering external pH inhibited efflux. At low external pH, external beta-hydroxybutyrate enhanced efflux slightly. At high external pH, external beta-hydroxybutyrate inhibited efflux. Internal acidification inhibited influx and internal alkalization enhanced influx. Internal beta-hydroxybutyrate (betaHB) enhanced influx more in acidified than alkalized cells. These data are compatible with coupled betaHB-/OH- exchange, betaHB- and OH- competing for influx, C:OH- moving faster than C: betaHB-, empty C being immobile. They are also compatible with coupled betaHB-/H+ copermeation, empty C moving inward faster than H+:C:betaHB-, H+:C being immobile, and C:betaHB- (without H+) being so unstable as not to be formed in significant amounts (relative to C, H+:C, and H+:C:betaHB-).

Animals↗
PubMed1984

Sensorimotor impairment and elevated levels of dopamine metabolites in the neostriatum occur rapidly after intranigral injection of 6-hydroxydopamine or gamma-hydroxybutyrate in awake rats.

The unilateral injection of 6-hydroxydopamine (8 micrograms) into the ventral tegmental area of awake rats produced a rapidly developing and irreversible sensory neglect to contralateral tactile stimuli. This neglect developed in a caudal to rostral direction on the affected body surface and coincided with significant elevation in the concentrations of dopamine and two of its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the ipsilateral neostriatum. The unilateral injection of procaine or gamma-hydroxybutyric acid (GHB) into the substantia nigra of awake animals also produced a contralateral neglect that developed in a caudal to rostral direction, but the behavioral effect of these drugs diminished within 1 hr. Concentrations of dopamine, dihydroxyphenylacetic acid and homovanillic acid in the neostriatum were markedly elevated during continuous infusions of procaine or gamma-hydroxybutyric acid. The extent of sensory neglect and changes in dopamine metabolism in the neostriatum varied according to the amount of gamma-hydroxybutyric acid injected into the nigra and according to the proximity of injections of gamma-hydroxybutyric acid to the pars compacta. The rapid onset of sensory neglect following microinjections of 6-hydroxydopamine, procaine or gamma-hydroxybutyric acid is consistent with the ability of each of these drugs to block the conduction of impulses in mesostriatal neurons and suggests that concomitant increases in levels of dopamine, dihydroxyphenylacetic acid and homovanillic acid in the neostriatum resulted from decreases in the release of dopamine coupled with increased synthesis of dopamine. These findings also indicate that the catabolism of dopamine to dihydroxyphenylacetic acid or homovanillic acid may originate intraneuronally, without prior release of dopamine and its recapture by mesostriatal terminals, if the flow of impulses in this pathway has been blocked.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

The effects of gamma-hydroxybutyrate on the membrane properties of guinea-pig pars compacta neurons in the substantia nigra in vitro.

The effects of gamma-hydroxybutyrate have been studied on the membrane properties of pars compacta neurons within the guinea-pig substantia nigra maintained in vitro. The effects of gamma-hydroxybutyrate are to (i) lower input resistance, (ii) hyperpolarize the cell membrane in a dose-dependent manner and (iii) facilitate calcium conductances. These effects are resistant to the blockade of sodium channels with tetrodotoxin and blockade of potassium channels with tetraethylammonium or 4-aminopyridine. Furthermore, these effects are only partially blocked by high doses of the GABA receptor antagonist bicuculline: indeed the effects of the GABA receptor agonist muscimol can be differentiated from those of gamma-hydroxybutyrate in that the latter is sensitive to application of barium ions. The results suggest that gamma-hydroxybutyrate acts to increase utilization of calcium, which in turn leads to an initiation of calcium-dependent events. The functional consequences of these effects of gamma-hydroxybutyrate are discussed with regard to its possible endogenous modulatory actions.

Animals↗
PubMedDate not supplied

Localization studies of gamma-hydroxybutyrate receptors in rat striatum and hippocampus.

Quantitative autoradiography using [3H] gamma-hydroxybutyrate was used in combination with anatomic and neurotoxic lesions to localize the gamma-hydroxybutyrate (GHB) receptors in the striatum and hippocampus of rat brain. 6-Hydroxydopamine (6-OHDA) lesions of the nigro-striatal pathway failed to reduce [3H] gamma-hydroxybutyrate binding in the striatum. In contrast, kainic acid (KA) lesions of the caudate-putamen (CPu) resulted in about 45% loss of binding. For hippocampus, lesions of septo-hippocampal pathway did not modify receptor density but intrahippocampal kainic acid injection largely attenuated (50%) [3H] GHB binding. These results demonstrate that gamma-hydroxybutyrate receptors in the CPu and dorsal hippocampus are principally located on intrinsic neurons which may participate in the functional expression of the role gamma-hydroxybutyrate has in these structures.

Animals↗
PubMed2005

The relationship of a high level of serum beta-hydroxybutyrate to cause of death.

To examine the state of ketoacidosis in relation to the cause of death, three kinds of ketone bodies (acetoacetate, beta-hydroxybutyrate and acetone) were measured in postmortem serum. Of 100 autopsy cases, 22 had ketone body increasing pathophysiological conditions, overlapped in some cases, namely a poorly-nourished state (10 cases), alcoholic fatty liver damage (10), diabetes (5) and infectious disease (5). Of the 3, 11, 7 and 15 cases in which the beta-hydroxybutyrate concentration was greater than 10,000, 1000-10,000, 500-1000 and 200-500 micromol/l, 3 (100%), 8 (73%), 3 (43%) and 5 (33%), respectively, had one or more pathophysiological conditions that usually produce ketone bodies. Of the 64 cases in which the beta-hydroxybutyrate concentrations were less than 200 micromol/l, only 3 (5%) had some of these conditions. Cases showing high levels of ketone bodies tended to have pathophysiological states that can produce them, although the level of beta-hydroxybutyrate and these states did not show parallel relationships. When autopsy findings fail to explain the cause of death, a diagnosis as death caused by ketoacidosis would be reasonable if the serum beta-hydroxybutyrate level is over 1000 micromol/l and the body has pathophysiological conditions that tend to increase ketone bodies.

3-Hydroxybutyric Acid↗
PubMed2000

Gamma-hydroxybutyric acid: an evaluation of its rewarding properties in rats and mice.

Gamma-hydroxybutyric acid, an endogenous compound present in mammalian brain and supposed to be a neurotransmitter or neuromodulator, has been shown to affect several aspects of dependence from some drugs of abuse. It has been successfully used in clinical practice to alleviate both alcohol and opiate withdrawal symptoms. The aim of this study was to investigate whether gamma-hydroxybutyric acid possesses rewarding properties by means of conditioned place preference and intravenous self-administration paradigms. In the present study, gamma-hydroxybutyric acid induced conditioned place preference in rats, was intravenously self-administered by drug-naive mice, and altered cocaine intravenous self-administration in rats. Although to date the physiological role of this compound still remains unclear, there is no doubt that gamma-hydroxybutyric acid, in addition to its proved effect on alcohol and opiate dependence, possesses reinforcing properties of its own and may interfere with the neurochemical events in the rewarding effects produced by psychostimulant drugs. Our investigation points out the abuse liability of this drug, suggesting the use of particular precaution in handling gamma-hydroxybutyric acid as a clinically useful drug.

Animals↗
PubMed2000

Mechanism of the antialcohol effect of gamma-hydroxybutyric acid.

Treatment with gamma-hydroxybutyric acid has been reported to effectively decrease alcohol craving and consumption as well as alcohol withdrawal symptoms in alcoholics. We describe the results of animal studies demonstrating the ability of gamma-hydroxybutyric acid to reduce (1) the severity of ethanol withdrawal signs in rats rendered physically dependent on ethanol and (2) voluntary ethanol intake in selectively bred Sardinian alcohol-preferring rats. Furthermore, we review experimental data suggesting that gamma-hydroxybutyric acid and ethanol have several pharmacological effects in common. Relevant similarities are: (1) stimulation of firing rate of dopaminergic neurons and dopamine release in specific rat brain areas; (2) development of cross-tolerance to the motor-impairing effects after repeated administration in rats; 3) abuse potential, as indicated by self-administration of pharmacologically relevant doses of gamma-hydroxybutyric acid in rats and mice; (4) induction of anxiolytic effects in rats; and (5) induction of similar discriminative stimulus effects, as evidenced by symmetrical generalization in a drug discrimination study in rats. These lines of evidence are discussed in relation to gamma-hydroxybutyric acid exerting its antialcohol effects by a substitution mechanism.

Alcohol Drinking↗
PubMed1982

[Sodium gamma-hydroxybutyrate. Effects on visual flash-evoked potentials].

Na gamma hydroxybutyrate being recognized as a mean of brain protection, the effect of Na gamma hydroxybutyrate on visual evoked potentials is studied in ten neurosurgical patients. Recordings are made in the same intensive care unit and with the same equipment. Latencies of the three principal peaks (III, IV, V) are analysed. No gamma hydroxybutyrate, given intravenously (60 mg . kg-1), significantly increased latencies (p less than 0,001). So, it must take into account of this effect when visual evoked potentials are studied in Na gamma hydroxybutyrate treated-patients. However, visual evoked potentials peaks are only delayed by Na gamma hydroxybutyrate and none of the studied peaks is abolished.

Brain Diseases↗
PubMed2002

Effects of acute inhibition of fatty acid oxidation on latency to seizure and concentrations of beta hydroxybutyrate in plasma of rats maintained on calorie restriction and/or the ketogenic diet.

The present study was designed to evaluate the effects of acute inhibition of fatty acid oxidation on plasma levels of beta hydroxybutyrate and latency to PTZ-induced seizures in ad libitum- (AL), calorie-restricted normal rodent chow- (CR), and calorie-restricted ketogenic diet (KD)-fed young rats. Young (day 23) Sprague-Dawley rats were fasted for 8 h and then fed their respective diets for 21 days. On day 21 of the diet rats in each group received either saline or the fatty acid oxidation inhibitor mercaptoacetate (MA; 46 mg/kg intraperitoneally (i.p.). Two hours later, all rats received pentylenetetrazole (PTZ; 10 mg/kg; i.p.) every 10 min until seizure onset. Results demonstrated that KD-fed rats had the longest (P<0.05) latency to PTZ-induced seizures. KD-fed rats administered an acute dose of MA had lower (P<0.01) levels of beta hydroxybutyrate in plasma and shorter latency to PTZ-induced seizures compared with control KD-fed rats. However, there was not a significant positive correlation (P>0.10) between plasma beta hydroxybutyrate and latency to seizure, suggesting that beta hydroxybutyrate may be indirectly involved in the antiseizure effects of the KD. Fatty acid oxidation inhibition represents an experimental manipulation that may allow for more precise establishment and evaluation of levels of beta hydroxybutyrate in plasma necessary for antiseizure effects of the KD.

3-Hydroxybutyric Acid↗
PubMed2003

High beta-hydroxybutyrate concentration in liver and skeletal muscle of newly hatched chicks.

Characteristic changes in ketone body concentrations in blood, liver, and skeletal muscle were investigated in detail in newly hatched chicks. The concentration of beta-hydroxybutyrate in the blood was maximal at hatch (0 day), markedly decreased to 3 days, then maintained at low levels, up to 14 days of age. The concentration of acetoacetate in blood, on the other hand, did not change after hatching but remained lower than that of beta-hydroxybutyrate at all ages. In liver and muscles, the concentration of beta-hydroxybutyrate changed in a manner similar to that in the blood. The muscle to blood ratio of the beta-hydroxybutyrate concentration on days -1 and 0 was significantly higher than those at 1 through 14 days post-hatch. These results show that newly hatched chicks have the same high ketone body concentrations in the skeletal muscle, blood and liver. It is, hence, suggested that uptake of beta-hydroxybutyrate by muscles is substantial or that ketogenesis, if any, occurs in muscles immediately before and after hatching of chicks.

3-Hydroxybutyric Acid↗
PubMed1981

Inhibition of D(--)-beta-hydroxybutyrate dehydrogenase by modifiers of disulfides, thiols, and vicinal dithiols.

D(--)-beta-hydroxybutyrate dehydrogenase of beef heart mitochondria catalyzes the reversible oxidation of D-(--)-beta-hydroxybutyrate to acetoacetate in the presence of NAD. Both the membrane-bound and the soluble forms of the enzyme are inhibited by modifiers of thiols [N-ethylmaleimide (NEM) and p-(chloromercuri)phenylsulfonate (pCMS)], vicinal dithiols [phenylarsine oxide and diazenedicarboxylic acid bis(dimethylamide) (diamide)], and disulfides (sulfite, sulfide, and cyanide). NAD and NADH, but not beta-hydroxybutyrate and acetoacetate, protect the enzyme against inhibition by NEM, pCMS, phenylarsine oxide, and diamide. As tested with NEM and diamide, the inhibitions caused by mono- and dithiol modifiers were pseudo first order, and the reaction order with respect to the concentration of either inhibitor was unity, thus indicating the modification of a single essential thiol and/or dithiol. Sulfite and sulfide inhibitions appeared to be competitive with respect to beta-hydroxybutyrate, with Ki values of 10-15 and about 240 microM, respectively. Sulfite inhibition was uncompetitive with respect to NAD, NADH, and acetoacetate. The above results have suggested the presence in D(--)-beta-hydroxybutyrate dehydrogenase of an essential thiol and/or a vicinal dithiol associated with the binding site(s) of NAD and NADH. The inhibition by sulfite, sulfide, and cyanide might be indicative of the presence of an essential disulfide or due to a ternary complex formation involving the enzyme, NAD, and the above nucleophiles.

Acetoacetates↗
PubMedDate not supplied

Studies on comonomer compositional distribution of bacterial poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)s and thermal characteristics of their factions.

The comonomer-unit compositional distributions have been investigated for bacterial poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(3HB-co-3HH)] samples with 3HH unit content of 13.8, 18.0, 22.0, and 54.0 mol %. They were comonomer compositionally fractionated using chloroform/n-heptane mixed solvent at ambient temperature. The fractionation of P(3HB-co-18.0 mol %3HH) and P(3HB-co-22.0 mol % 3HH), which could not be carried out effectively at room temperature, were refractionated at 70 degrees C in the mixed solvent. Fractions with different 3HH unit content in a wide range (from 4.4 to 80.7 mol %) were obtained. By use of these fractions with narrow compositional distribution, the comonomer composition dependence of thermal properties was investigated by differential scanning calorimetry. The melting point (T(m)) and heat of fusion (DeltaH) decreased as the 3HH unit content increased in the range of low 3HH content (<40 mol %), while they increased as the 3HH unit content increased in the high 3HH content range (>70 mol %). The minimum T(m) and DeltaH values were found to exist at 3HH unit content of about 60 mol %. The glass transition temperature (T(g)) decreased linearly with the increase of 3HH unit content. The values of T(m), DeltaH, and T(g) of P(3HB-co-3HH)s were compared with those of poly(3-hydroxybutyrate-co-3-hydroxyvalerate), poly(3-hydroxybutyrate-co-3-hydroxypropionate), and poly(3-hydroxybutyrate-co-4-hydroxybutyrate), and the effects of comonomer types on the thermal properties were revealed.

3-Hydroxybutyric Acid↗
PubMed1967

Rates of entry and oxidation of acetate, glucose, D(-)-beta-hydroxybutyrate, palmitate, oleate and stearate, and rates of production and oxidation of propionate and butyrate in fed and starved sheep.

1. Rates of entry and oxidation of a range of metabolites have been measured in tracheostomized sheep (diet, 800g. of lucerne chaff and 100g. of maize/day) by combining isotope-dilution techniques with the continuous measurement of total respiratory gas exchange, and (14)CO(2) production during the intravenous or intraruminal infusion of (14)C-labelled substrates. 2. Mean entry rates in fed and starved (24hr.) sheep respectively, expressed as mg./min./kg. body wt.(0.75), were: glucose, 5.0 (range 4.8-5.1, 2 observations) and 3.8 (3.2-4.2, 4); acetate, 10.8 (9.1-13.5, 4) and 5.8 (1); d(-)-beta-hydroxybutyrate, 1.4 (1) and 1.5 (0.8-2.4, 4); palmitate, oleate and stearate (starved sheep only) 1.0 (0.6-1.9, 7), 0.9 (0.2-1.6, 10) and 0.9 (0.5-1.1, 11) respectively. 3. Production rates of propionate and butyrate in continuously feeding sheep were 6.4 (4.7-8.3, 4) and 4.3 (3.4-6.1, 4) mg./min./kg.(0.75) respectively, and in starved (24hr.) sheep were 2.5 (2.2-2.9, 2) and 1.0 (0.8-1.2, 2) mg./min./kg.(0.75) respectively. 4. Calculated terminal values for the specific radioactivity of respiratory (14)CO(2) during measurements of entry rates and production rates were used to calculate the contributions of individual substrates to overall oxidative metabolism. Mean values for fed and starved sheep respectively were: glucose, 9.1 (8.6-9.6, 2) and 11.2 (5.9-15.1, 4)%; acetate, 31.6 (26.8-38.1, 4) and 22.1 (1)%; d(-)-beta-hydroxybutyrate, 10.4 (1) and 4.8 (1.9-7.7, 4)%; propionate, 23.0 (13.8-29.9, 4) and 7.1 (6.8-7.4, 2)%; butyrate, 16.5 (13.7-20.5, 4) and 5.3 (5.2-5.3, 2)%; palmitate, oleate and stearate (starved sheep only), 4.7 (2.0-7.7, 7), 4.0 (1.2-6.6, 10) and 4.4 (3.8-5.8, 9)% respectively. The sum of these values for individual substrates in fed and starved sheep, excluding that of beta-hydroxybutyrate and after correction of the glucose value for the known interrelations of this substrate with propionate, accounted for 76% and 58% respectively of total production of carbon dioxide. 5. Calculations based on the proportion of substrate entry directly oxidized indicated that the substrates studied accounted for 63% (fed sheep) and 43% (starved sheep) of total energy expenditure measured by oxygen uptake. The contribution of beta-hydroxybutyrate was excluded, and corrections were made for glucose-propionate interrelations, and for the different rates of oxidation of the methyl and carboxyl fragments of acetate. 6. The present results have been combined with those obtained earlier in this Laboratory to examine the relationships between rates of substrate entry and oxidation, and concentrations of substrate in blood. Rates of entry of acetate, glucose, d(-)-beta-hydroxybutyrate, palmitate and oleate (but not stearate) were well correlated with concentration in blood, and substrate contribution to production of carbon dioxide showed a similar correlation to blood concentration, except with glucose. 7. It was concluded that the general technique is of potential value in providing valid quantitative parameters of animal metabolism.

Acetates↗
PubMed1986

Decreased rate of ketone-body oxidation and decreased activity of D-3-hydroxybutyrate dehydrogenase and succinyl-CoA:3-oxo-acid CoA-transferase in heart mitochondria of diabetic rats.

Heart mitochondria from chronically diabetic rats ('diabetic mitochondria'), in metabolic State 3, oxidized 3-hydroxybutyrate and acetoacetate at a relatively slow rate, as compared with mitochondria from normal rats ('normal mitochondria'). No significant differences were observed, however, with pyruvate or L-glutamate plus L-malate as substrates. Diabetic mitochondria also showed decreased 3-hydroxybutyrate dehydrogenase and succinyl-CoA: 3-oxoacid CoA-transferase activities, but cytochrome content and NADH-dehydrogenase, succinate dehydrogenase, cytochrome oxidase and acetoacetyl-CoA thiolase activities proved normal. The decrease of 3-hydroxybutyrate dehydrogenase activity was observed in diabetic mitochondria subjected to different disruption procedures, namely freeze-thawing, sonication or hypoosmotic treatment, between pH 7.5 and 8.5, at temperatures in the range 6-36 degrees C, and in the presence of L-cysteine. Determination of the kinetic parameters of the enzyme reaction in diabetic mitochondria revealed diminution of maximal velocity (Vmax) as its outstanding feature. The decrease in 3-hydroxybutyrate dehydrogenase in diabetic mitochondria was a slow-developing effect, which reached full expression 2-3 months after the onset of diabetes; 1 week after onset, no significant difference between enzyme activity in diabetic and normal mitochondria could be established. Insulin administration to chronically diabetic rats for 2 weeks resulted in limited recovery of enzyme activity. G.l.c. analysis of fatty acid composition and measurement of diphenylhexatriene fluorescence anisotropy failed to reveal significant differences between diabetic and normal mitochondria. The Arrhenius-plot characteristics for 3-hydroxybutyrate dehydrogenase in membranes of diabetic and normal mitochondria were similar. It is assumed that the variation of the assayed enzymes in diabetic mitochondria results from a slow adaptation to the metabolic conditions resulting from diabetes, rather than to insulin deficiency itself.

Animals↗
PubMed1987

3-Hydroxyisobutyrate dehydrogenase, an impurity in commercial 3-hydroxybutyrate dehydrogenase.

The enzymic determination of D-3-hydroxybutyrate and acetoacetate normally involves the use of 3-hydroxybutyrate dehydrogenase (HBDH, EC 1.1.1.30) of bacterial origin. We show that HBDH from Rhodopseudomonas spheroides (BCL, grade II) contains a 3-hydroxyisobutyrate dehydrogenase (HIBDH) activity: activity with 3-hydroxyisobutyrate as substrate was greater than 10% of that with 3-hydroxybutyrate. However, HBDH could be prepared essentially free of HIBDH activity by incubation at 37 degrees C in the presence of 1 mM-CaCl2, to produce an enzyme preparation that may be used for the specific determination of 3-hydroxybutyrate. Use of the purified enzyme preparations indicated that a major product of valine metabolism in hemidiaphragms from 40 h-starved rats was 3-hydroxyisobutyrate rather than 3-hydroxybutyrate.

Animals↗
PubMed2002

[2,4-13 C2 ]-beta-Hydroxybutyrate metabolism in human brain.

Infusions of [2,4-13C2]-beta-hydroxybutyrate and 1H-13C polarization transfer spectroscopy were used in normal human subjects to detect the entry and metabolism of beta-hydroxybutyrate in the brain. During the 2-hour infusion study, 13C label was detectable in the beta-hydroxybutyrate resonance positions and in the amino acid pools of glutamate, glutamine, and aspartate. With a plasma concentration of 2.25 +/- 0.24 mmol/L (four volunteers), the apparent tissue beta-hydroxybutyrate concentration reached 0.18 +/- 0.06 mmol/L during the last 20 minutes of the study. The relative fractional enrichment of 13C-4-glutamate labeling was 6.78 +/- 1.71%, whereas 13C-4-glutamine was 5.68 +/- 1.84%. Steady-state modeling of the 13C label distribution in glutamate and glutamine suggests that, under these conditions, the consumption of the beta-hydroxybutyrate is predominantly neuronal, used at a rate of 0.032 +/- 0.009 mmol. kg-1. min-1, and accounts for 6.4 +/- 1.6% of total acetyl coenzyme A oxidation. These results are consistent with minimal accumulation of cerebral ketones with rapid utilization, implying blood-brain barrier control of ketone oxidation in the nonfasted adult human brain.

3-Hydroxybutyric Acid↗
PubMed2004

Urinary acetoacetate or capillary beta-hydroxybutyrate for the diagnosis of ketoacidosis in the Emergency Department setting.

OBJECTIVES: We compared the semiquantitative measurement of acetoacetate using urinary dipsticks with the bedside quantitative fingerprick measurement of the principal ketone bodies 3-beta-hydroxybutyrate, for the diagnosis of ketoacidosis. METHODS: This is a one year retrospective study of patients who presented with hyperglycemia levels of 250 mg/l or greater in the Emergency Department setting. We compared the sensitivity, specificity, and predictive value of ketonuria and ketonemia for the diagnosis of ketoacidosis (urine or blood ketone bodies, blood bicarbonates <20 mmol/l, anion gap >16 meq/l) in a sample of patients for whom the levels of ketone bodies in the blood and urine as well as serum electrolytes were available. RESULTS: We studied 355 hyperglycemic patients. The median time between arrival and dipstick testing was 21 min, and was greater than 2 h in more than 10% of cases. Comparison between ketonuria and ketonemia was performed in 173 patients (6% with diabetic ketoacidosis). Ketonuria equal to or less than one cross or a 3-beta-hydroxybutyrate value lower than 3 mmol/l enabled ketoacidosis to be excluded (negative predictive value 100%). At two-cross cutoff points for ketonuria and at the 3 mmol/l cutoff point for ketonemia, the two tests had the same sensitivity (100%), but the specificity of 3-beta-hydroxybutyrate (94%) was significantly higher (P<0.0001) than that of ketonuria (77%). The best positive predictive value for ketonemia was obtained at the 5 mmol/l cutoff point (100%) and for ketonuria at the three-cross cutoff point (26%). At the three-cross cutoff point for ketonuria and at the 5 mmol/l cutoff point for ketonemia, the two tests had the same negative likelihood ratio (0.1), but the positive likelihood ratio of 3-beta-hydroxybutyrate (infinite) was higher than that of ketonuria. CONCLUSION: The measurement of 3-beta-hydroxybutyrate in capillary blood is faster and more effective than the use of dipsticks in the urine to detect ketoacidosis in the Emergency Department setting.

3-Hydroxybutyric Acid↗