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PubMed1978

Acetoacetate metabolism in rat brain. Development of acetoacetyl-coenzyme A deacylase and 3-hydroxy-3-methylglutaryl-coenzyme A synthase.

1. Data are provided that indicate that the rat brain acetoacetyl-CoA deacylase is almost exclusively mitochondrial. Developmental studies show that this enzyme more than doubles its activity during suckling (0--21 days) and then maintains this activity in adults (approx. 1.1 units/g wet wt.). 2. Kinetic studies (on the acetoacetyl-CoA deacylase) in a purified brain mitochondrial preparation give a Vmax. of 47 nmol/min per mg of protein, and a Km for acetoacetyl-CoA of 5.2 micron and are compatible with substrate inhibition by acetoacetyl-CoA above concentrations of 47 micron. 3. The total brain 3-hydroxy-3-methyl-glutaryl-CoA synthase remains constant in the developing and adult rat brain (approx. 1.2 units/g wet wt.). This enzyme is located in both the mitochondrial and cytosolic fractions. During suckling (0--21 days) the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase represents approx. one-third of the total, but this increases markedly to about 60% of the total in the adult. The cytosolic enzyme correspondingly falls to approx. 40% of the total. 4. The role of the acetoacetyl-CoA deacylase in providing cytosolic acetoacetate for biosynthetic activities in the developing brain is discussed.

Acetoacetates↗
PubMed1980

Oxygen consumption in perfused skeletal muscle. Effect of perfusion with aged, fresh and aged-rejuvenated erythrocytes on oxygen consumption, tissue metabolites and inhibition of glucose utilization by acetoacetate.

1. O2 consumption, glucose metabolism and the energy status of skeletal muscle were compared in isolated rat hindquarters perfused with aged (21--35 days), fresh and aged-rejuvenated human erythrocytes. 2. The age of the erythrocytes did not affect O2 consumption, glucose utilization or lactate release either at rest or during exercise. The concentrations of ATP, phosphocreatine and lactate within the muscle were also unaffected by the use of aged erythrocytes. 3. Perfusion with acetoacetate did not inhibit glucose utilization; but, it caused a marked increase in the tissue concentration of citrate in the soleus, a slow-twitch red muscle, and a smaller increase in the gastrocnemius, which contains fast-twitch red and white fibres. Results were similar in hindquarters perfused with aged and aged-rejuvenated erythrocytes. 4. These findings suggest that perfusion with aged human erythrocytes does not cause major alterations in the metabolic performance of the isolated rat hindquarter.

Acetoacetates↗
PubMed1984

Turnover of succinyl-CoA:3-oxoacid CoA-transferase in glioma and neuroblastoma cells. Specific influence of acetoacetate in neuroblastoma cells.

The specific activity of succinyl-CoA:3-oxo-acid CoA-transferase (3-oxoacid CoA-transferase, EC 2.8.3.5) increases significantly during growth in culture in both mouse neuroblastoma N2a and rat glioma C6 cells. To investigate the mechanism(s) responsible for this, antibody specific for rat brain 3-oxoacid CoA-transferase was raised in rabbits. Immunotitrations of 3-oxoacid CoA-transferase from neuroblastoma and glioma cells on days 3 and 7 of growth after subculture showed that the ratio of 3-oxoacid CoA-transferase activity to immunoprecipitable enzyme protein remained constant, indicating that differences in specific activity of the enzyme at these times in both cell types reflect differences in concentration of enzyme protein. In glioma cells, the relative rate of 3-oxoacid CoA-transferase synthesis was about 0.04-0.05% throughout 9 days in culture. In contrast, the relative rate of synthesis of 3-oxo-acid CoA-transferase in neuroblastoma cells was about 0.07-0.08% on days 3, 5 and 7 after subculture, but fell to 0.052% on day 9. The degradation rates of total cellular protein (t1/2 = 28 h) and 3-oxoacid CoA-transferase (t1/2 = 46-50 h) were similar in both cell lines. The rise in specific activity of the enzyme in both cell lines from days 3 to 7 without a significant increase in the relative rate of synthesis reflects a slow approach to steady-state conditions for the enzyme secondary to its slow degradation. Differences in 3-oxoacid CoA-transferase specific activity between the two cell lines are apparently due to a difference of about 60% in relative rates of enzyme synthesis. The presence of 0.5 mM-acetoacetate in the medium significantly increased the specific activity of 3-oxoacid CoA-transferase in neuroblastoma cells during the early exponential growth phase. This treatment increased the relative rate of synthesis of 3-oxoacid CoA-transferase by 23% (P less than 0.025) in these cells on day 3, suggesting that substrate-mediated induction of enzyme synthesis is a mechanism of regulation of 3-oxoacid CoA-transferase.

3-Hydroxybutyric Acid↗
PubMed2002

Acetoacetate, acetone, and dibenzylamine (a contaminant in l-(+)-beta-hydroxybutyrate) exhibit direct anticonvulsant actions in vivo.

PURPOSE: To investigate whether ketone bodies are directly anticonvulsant. METHODS: We tested the effects of acetoacetate (ACA), acetone, and both stereoisomers, D-(-)- and L-(+), of beta-hydroxybutyrate (BHB) on sensory-evoked seizures in Frings audiogenic seizure-susceptible mice. RESULTS: We found that these ketone bodies, with the exception of the D-(-)-isomer of BHB, were anticonvulsant in this model. Furthermore, with gas chromatography-mass spectrometry, we confirmed that the activity of L-(+)-BHB was due to dibenzylamine, a chemical contaminant. CONCLUSIONS: Our data indicate that the anticonvulsant efficacy of the ketogenic diet may be due in part to the direct actions of ACA and acetone.

3-Hydroxybutyric Acid↗
PubMed1979

Monoglyceryl acetoacetate: a ketone body-carbohydrate substrate for parenteral feeding of the rat.

The monoglyceride of acetoacetate was prepared from diketene and glycerol. The resulting mixture was composed of nearly equal amounts of 1- and 2-monoacetoacetin. This mixture was tested as a parenteral energy substrate by continuous intravenous infusion into the rat. This glyceride provided 71% of the daily energy for 7 consecutive days. Other groups were either fed ad libitum or fed ad libitum and supplemented with intravenous glucose isoenergetic to monoacetoacetin. All three groups had similar daily non-protein energy intake, and the two supplemented groups ate less protein than normal rats. All three groups gained weight similarly although the glucose group tended to gain fastest and the monoacetoacetin group tended to gain slowest. The rates were not significantly different. At the end of 7 days, the glucose group was hyperglycemic and the monoacetoacetin group was hyperketonemic compared to normal fed rats. The only significant differences among the livers was the small size found for the glucose group. Hepatic compositions were similar. It was concluded from these data that intravenous monoacetoacetin can support weight gain in rats and is a potential alternative to glucose as an energy source in parenteral nutrition.

Acetoacetates↗
PubMed1984

Parenteral feeding at two hypocaloric levels for comparison of glucose-glycerol mixture with the monoglyceride of acetoacetate on urinary nitrogen losses of the rat.

The monoglyceride of acetoacetate (monoacetoacetin) is a synthetic compound that might serve to reduce the glucose contribution to nonprotein energy in total parenteral nutrition provided it is an effective nutritional source. This study compared monoacetoacetin and glucose-glycerol mixtures as energy in hypocaloric, parenteral feeding of the rat. Four groups of rats were infused with approximately 425 mg N/day along with 11 or 21 kcal/day supplied either by monoacetoacetin or the glucose-glycerol mixture. Body weight and urinary nitrogen were followed for 7 days, and leucine kinetics was measured on day 7. At 11 or 21 kcal/day, rats infused with the monoacetoacetin or the glucose-glycerol mixture had similar body weight losses, urinary nitrogen losses, leucine flux and leucine oxidation rates. When rats receiving the same energy substrate at 11 or 21 kcal/day were compared, the rats receiving the 21 kcal/day by vein lost less body weight and less urinary nitrogen and had a smaller leucine flux. The leucine oxidation rate was unchanged. These data demonstrate that alterations in nitrogen parameters are dependent on the quantity of energy but are independent of the source of energy when monoacetoacetin and glucose-glycerol mixtures are compared. Monoacetoacetin interacts with nitrogen metabolism in healthy rats as effectively a glucose-glycerol mixtures at the hypocaloric levels studied.

Acetoacetates↗
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↗
PubMed1977

Tubular reabsorption and urinary excretion of acetoacetate and 3-hydroxybutyrate in normal subjects and juvenile diabetics.

The renal handling of acetoacetate (AA) and 3-hydroxybutyrate (3-HB) has been examined in 8 normal subjects and 7 insulin-treated juvenile diabetics before and after i.v. infusion of sodium DL-3-hydroxybutyrate. In both normals and diabetics and ketone bodies were reabsorbed. At low filtration rates of AA and 3-HB the reabsorption was nearly complete. With increasing filtration rate both the tubular reabsorption rate and the urinary excretion rate of AA and 3-HB increased linearly. A maximal tubular reabsorption rate could not be demonstrated. In spite of higher filtration rates of AA and 3-HB in the diabetics, the mean reabsorption percentage of either ketone body did not differ from that found in the normals.

Acetoacetates↗
PubMed2004

Acetoacetate activation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase in primary cultured rat hepatocytes: role of oxidative stress.

Diabetes is characterized by elevated levels of ketone bodies acetoacetate (AA) and 3-hydroxybutyrate (3HB). High levels of ketone bodies have been implicated in generation of cellular oxidative stress. Ketone body activation of cellular signaling pathways associated with oxidative stress, however, has not been established. Thus, ketone body effects on kinase activation in primary cultured rat hepatocytes have been examined. Treatment with AA increased the phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2) and p38 mitogen-activated protein kinase (MAPK), maximally by approximately 2.5- and 4-fold, respectively. AA failed to activate c-Jun NH(2)-terminal kinase. AA-mediated Erk1/2 and p38 MAPK activation was detectable at 3 h post-treatment with maximal activation occurring at 12 h. In contrast, 3HB failed to activate any of these kinases. Elevated phosphorylation of Raf and MKK3/6 also occurred in response to AA. Bisindolylmaleimide, a generalized protein kinase C (PKC) inhibitor, and B581, a Ras farnesylation inhibitor, inhibited AA-mediated activation of Erk1/2 and p38 MAPK, suggesting a role for PKC and Ras in mediating such activation. Interestingly, the tyrosine kinase inhibitor genistein prevented the AA-mediated phosphorylation of Erk1/2, but not p38 MAPK. AA treatment resulted in the generation of reactive oxygen species (ROS) and the depletion of cellular glutathione levels, which was ameliorated by the antioxidants N-Acetyl-l-cysteine (NAC) and Trolox (6-hydroxy-2,5,7,8-tetramethyl-chroman-2-carboxylic acid). NAC and Trolox also ameliorated AA-mediated Erk1/2 and p38 MAPK activation, suggesting that this activation is associated with ROS and oxidative stress.

Acetoacetates↗
PubMed2005

Acetoacetate induces CYP2E1 protein and suppresses CYP2E1 mRNA in primary cultured rat hepatocytes.

The ketone body acetoacetate (AA) in the absence of insulin or in the presence of diabetic insulin levels decreases CYP2E1 mRNA expression in a concentration- and time-dependent manner in primary cultured rat hepatocytes. AA activates p70 ribosomal S6 kinase (p70S6K) and protein kinase C (PKC) by approximately 2- to 2.5-fold, respectively, following 6-h treatment. The AA-mediated activation of p70S6K, but not PKC, was abolished by inhibition of PI 3-K with LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] or wortmannin, in agreement with p70S6K being downstream of phosphatidylinositol 3-kinase (PI 3-K). Inhibition of PI 3-K, mTOR with rapamycin, or PKC with bisindolylmaleimide ameliorated the AA-mediated down-regulation of CYP2E1 mRNA expression. Neither the mitogen-activated protein kinase kinase inhibitor PD98059 (2'-amino-3'-methoxyflavone) nor the p38 mitogen-activated protein kinase inhibitor SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole] ameliorated the AA-mediated suppression of CYP2E1 mRNA expression. Heterogeneous nuclear RNA analysis revealed that AA suppressed CYP2E1 gene transcription by approximately 50% and that inhibition of PI 3-K and PKC diminished this AA-mediated effect on transcription. CYP2E1 mRNA half-life slightly increased from approximately 24 h in untreated hepatocytes to approximately 32 h in AA-treated cells. Interestingly, AA increased CYP2E1 protein levels by approximately 2- and 2.5-fold at 24 and 48 h, respectively. DL-beta-hydroxybutyrate was without effect. Polysomal distribution studies revealed that AA increased the proportion of RNA associated with the actively translated polysomal fractions versus the 40S to 60S untranslated fractions by approximately 40%. CYP2E1 protein half-life increased from approximately 8 h in untreated hepatocytes to approximately 24 in AA-treated cells. These data show that AA decreases CYP2E1 mRNA expression through inhibition of gene transcription while simultaneously elevating CYP2E1 protein levels through increased translation and decreased protein degradation.

Acetoacetates↗
PubMed1985

Acetoacetate and 3-hydroxybutyrate kinetics in obese and insulin-dependent diabetic humans.

[3-14C]acetoacetate (AcAc) and beta-[3-14C]hydroxybutyrate (beta-OHB) administration, measurements of labeled AcAc and beta-OHB in blood, and kinetic modeling have been used to investigate ketone body (KB) metabolism in five normal, five obese, and eight insulin-withdrawn diabetic subjects. Diabetic subjects were divided in mildly ketotic (MKD) and highly ketotic (HKD) patients according to beta-OHB blood level. A four-compartmental model successfully described the tracer kinetic data in obese and normal subjects, whereas in diabetic patients a five-compartmental model was necessary. Obese subjects showed a significantly lower (P less than 0.05) KB de novo synthesis (R30 = 159 +/- 54 (SD) mumol X min-1 X m-2) in comparison with normal subjects (282 +/- 93), but the clearance rates of AcAc (PCR1) and beta-OHB (PCR2) were similar in the two groups. R30 was 596 +/- 534 in MKD and 1,278 +/- 445 (P less than 0.01) in HKD. PCR1 was not significantly different both in MKD and HKD in comparison with normal subjects. In contrast PCR2 was markedly reduced in HKD (0 +/- 0 ml X min-1 X m-2) in comparison with MKD (1,031 +/- 615) and normal subjects (782 +/- 278). The percentage distribution of KB among various tissues inside the organism of diabetic subjects is abnormal. Both AcAc and beta-OHB recycling and mean residence time are not normal in HKD. A significant correlation was found between C-peptide and KB production in diabetes. These results suggest that a selective defect of beta-OHB peripheral utilization is important in determining and maintaining severe diabetic ketoacidosis.

3-Hydroxybutyric Acid↗
PubMed1985

Renal hydroxybutyrate and acetoacetate reabsorption and utilization in the rat.

Is the renal conservation of ketones effected through saturable transport systems? Does the renal reabsorption of ketoacids limit their utilization? The reabsorptive transport (T) and metabolic utilization (Q) of D-3-hydroxybutyrate (HB) and acetoacetate (AA) in the kidney were measured in anesthetized rats by use of clearance and arteriovenous extraction determinations. THB and TAA increased in proportion with increasing HB and AA filtered loads. Fractional THB decreases from 0.97 to 0.72 upon increases in the plasma HB. Fractional TAA also decreases from 0.89 to 0.73, at a constant filtered AA load, when the filtered HB load increased. Thus both saturable and nonsaturable components effect the reabsorption of HB and AA. Renal QHB increased from 0.4 to 4 mumol X g-1 X min-1 on increase in the plasma HB. THB always exceeded the simultaneously measured QHB. However, QHB was significantly correlated with THB, suggesting that QHB may be limited by delivery of HB to the renal cells through reabsorptive pathways. There was no net renal conversion of HB and AA. Both HB and AA were utilized by the kidney. Thus, utilized ketoacids must have entered pathways for complete oxidation or for synthesis (lipid?) in the kidney.

3-Hydroxybutyric Acid↗
PubMed1986

Renal reabsorption and utilization of hydroxybutyrate and acetoacetate in starved rats.

Are there increases in the renal reabsorption (R) and utilization (Q) of ketoacids during starvation? R and Q of D-3-hydroxybutyrate and acetoacetate were measured in anesthetized normally fed (C) and 3-day starved (S) rats, using clearance and arteriovenous extraction methods. R was nearly complete in both groups at low filtered ketoacids loads (less than 2mumol/g X min). At higher filtered loads, R of the two ketoacids increased in proportion to their filtered loads (r2 greater than 0.95) but with significantly steeper slopes in the S than in the C group; fractional R of the two ketoacids were significantly higher in the S than in the C animals. Saturable and nonsaturable components for ketoacid reabsorption were evident, but only the nonsaturable component was significantly increased with starvation. Increased R of ketoacids during starvation was in the absence of changes in the initial rates of hydroxybutyrate influx into isolated rat renal brush-border membrane vesicles. Thus the rate-limiting step for ketoacid reabsorption through the nonsaturable pathway may not be located at the luminal membrane of the proximal cells. The increases in R of ketoacids in the S group were associated with simultaneous decreases in the net rates of renal utilization of the two ketoacids. Thus increased renal conservation of ketoacids is a transport and not a metabolic event. Overall, during complete starvation, both the increased R and the decreased renal Q of the ketoacids contribute to increase the availability of these metabolites to other organs.

Absorption↗
PubMed1992

Transport of beta-hydroxybutyrate and acetoacetate along rat nephrons: a micropuncture study.

The transport of ketone bodies across the luminal membrane of the nephron was studied by means of micropuncture techniques in rats in normal acid-base state. The concentration of beta-hydroxybutyrate (beta-HB) and acetoacetate (AcAc) in plasma, tubular fluid and urine was measured by an ultramicromethod using enzymatic cycling. At endogenous plasma ketone body concentration, approximately 80% of the filtered load of beta-HB and AcAc was reabsorbed in the proximal convoluted tubule, the remaining fraction being almost completely reabsorbed between the late proximal convoluted and the distal tubule; under these conditions, the urinary excretion of ketone bodies was less than 1% of the filtered load. A progressive elevation to steady-state levels of plasma beta-HB resulted in a progressive reduction of the fractional reabsorption of beta-HB and AcAc in the proximal convoluted tubule, which means that reabsorption of ketone bodies in this nephron segment is saturable. No net secretion of ketone bodies could be demonstrated along the nephron even at the highest plasma ketone body concentrations reached. In clearance experiments, the capacity of the rat kidney for reabsorbing both beta-HB and AcAc was found to be limited by a maximal tubular capacity (Tm). The data suggest that, in the young Wistar rat nephron, most of the reabsorption of ketone bodies is carrier mediated.

3-Hydroxybutyric Acid↗
PubMed1997

Effect of carbonic anhydrase inhibition and acetoacetate on anaplerotic pyruvate carboxylase activity in cultured rat astrocytes.

In peripheral tissues, carbonic anhydrase (CA) inhibition secondarily decreases the anaplerotic activity of pyruvate carboxylase activity leading to a decline in citric acid cycle intermediates and glutamate. In view of the important role of pyruvate carboxylase in the brain, we examined the effects of CA inhibition on pyruvate-carboxylase-mediated [14C]CO2 fixation in cultured astrocytes from postnatal rat brains. Incubation with H[14C]O3 led to radiolabeling of metabolites found both in the cells and in the medium. These were separated by ion exchange chromatography for identification. Ethoxyzolamide (ETZ), a sulfonamide CA inhibitor (SCAI) with a heterocyclic side group, caused a 43-73% decrease in cell lysate [alpha-ketoglutarate] and 14C incorporation into major products of pyruvate carboxylation in the cell lysates and cell medium (i.e., released products). Half-maximal inhibition of [14C]CO2 fixation was observed between 1 and 3 x 10(7) M. This is similar to the IC50 value for ETZ inhibition of events in other cells that are thought to be mediated by CA. Inhibition was also observed with trifluormethanesulfonamide, an aliphatic SCAI, providing further evidence that this effect is mediated by CA. Western blot analysis using isozyme-specific antisera indicated that astrocytes contain CA II, a cytosolic isozyme, but CA III, CA IV and CA V could not be detected. This finding is unusual since the effects of SCAIs on pyruvate carboxylation in other tissues have been attributed to inhibition of the intramitochondrial isozyme. CA V. [14C]CO2 fixation was also decreased by lowering media [pyruvate] or by addition of 5 mM acetoacetate. It is hypothesized that SCAIs may inhibit pyruvate carboxylation in astrocytes by limiting the supply of bicarbonate to this enzyme while ketone bodies, by inhibiting glucose oxidation, may limit the supply of pyruvate. Interestingly, both SCAIs and ketogenic diets are used to treat adolescent forms of epilepsy. The possibility that these treatments might ultimately work by affecting anaplerotic pyruvate carboxylase activity in the brain is discussed.

Acetoacetates↗
PubMed1986

Comparison of monoglyceryl acetoacetate and glucose as parental energy substrate after experimental trauma.

The effects of ketone bodies and glucose on nitrogen balance and liver protein synthesis were studied in rat after experimental trauma. Energy was delivered intravenously as either monoglyceryl acetoacetate (MA; 87.5% of total energy input) or glucose (G). The isocaloric infusions (132 kcal/kg/day) were started after recovery from anaesthesia and continued for 2 days. The liver protein synthesis was then measured in vitro by perfusion with 14C-leucine. The infusion of MA resulted in a more negative cumulative nitrogen balance (MA: -2.31 +/- 0.26 g N/kg, G: -1.32 +/- 0.43 g N/kg/48 h; mean +/- SD) and liver protein synthesis (MA: 43.4 +/- 17.2, G: 71.1 +/- 15.2; arbitrary units, mean +/- SD). The results indicate no benefits from MA during the immediate post-traumatic period.

Acetoacetates↗
PubMed1977

Fasting plasma levels of glucose, acetoacetate, D-beta-hydroxybutyrate, glycerol, and lactate in the baboon infant: correlation with cerebral uptake of substrates and oxygen.

The energy-rich substrates available to the fasting stressed baboon neonate and infant are quantitatively similar to the metabolic fuels presented to the stressed low birth weight human newborn. Within a few hours after birth, fasting arterial plasma glucose levels in the baboon neonate approximate those of 4-6-week-old baboon infants after a 20-hr fast. Lactate levels are high and comparable for both age groups. In contrast, beta-hydroxybutyrate is quite low in the immediate neonatal period, but rises to significantly higher levels (P less than 0.001) after a fast at 4-6 weeks. In addition, glycerol levels are higher (P less than 0.02) in the fasted older infant compared with the fasting neonate. Computation of mean cerebral blood arteriovenous differences and oxygen equivalents for animals studied in the first 50 hr of life demonstrates that glucose uptake can account for 50% or less of cerebral oxygen consumption in the newborn period. In confirmation, the respiratory quotient in these animals is 0.52 +/- 0.06. Cerebral oxygen consumption in the immediate neonate is greater than can be explained by utilization of glucose and the small quantities of acetoacetate and beta-hydroxybutyrate available at this time. At birth, cerebral uptake of lactate is noted, but this phenomenon is not observed at 6 and 12 weeks of age.

Acetoacetates↗