scholarly journals Activities of enzymes of fat and ketone-body metabolism and effects of starvation on blood concentrations of glucose and fat fuels in teleost and elasmobranch fish

1979 ◽  
Vol 184 (2) ◽  
pp. 313-322 ◽  
Author(s):  
Victor A. Zammit ◽  
Eric A. Newsholme
Keyword(s):  
Fatty Acids ◽  
Ketone Body ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Ketone Bodies ◽  
Carnitine Palmitoyltransferase ◽  
Blood Metabolites ◽  
Activity Data ◽  
Blood Concentrations ◽  
Esterified Fatty Acids ◽  
Coa Transferase

1. Activities of 3-oxo acid CoA-transferase and carnitine palmitoyltransferase together with tri- and di-acylglycerol lipase were present in red and heart muscles of the teleost fish. However, d-3-hydroxybutyrate dehydrogenase activity was not detectable. These results suggest that the heart and red muscles of the teleosts should be able to utilize the fat fuels triacylglycerol, fatty acids or acetoacetate, but not hydroxybutyrate. The muscles from the elasmobranchs differed in that d-3-hydroxybutyrate dehydrogenase and 3-oxo acid CoA-transferase activities were present, but carnitine palmitoyltransferase activity was not detectable. This suggests that ketone bodies are the most important fat fuels in elasmobranchs. 2. The concentrations of acetoacetate, 3-hydroxybutyrate, glycerol, non-esterified fatty acids and triacylglycerols were measured in blood or plasma of several species of fish (teleosts and elasmobranchs) in the fed state. Teleosts have a 10-fold higher concentration of plasma non-esterified fatty acids, but a lower blood concentration of ketone bodies; both acetoacetate and 3-hydroxybutyrate are present in blood of elasmobranchs, whereas 3-hydroxybutyrate is absent from that of the teleosts. 3. The effects of starvation (up to 150 days) on the concentrations of blood metabolites were studied in a teleost (bass) and an elasmobranch (dogfish). In the bass there was a 60% decrease in blood glucose after 100 and 150 days starvation. In dogfish there was a large increase in the concentration of ketone bodies, whereas in bass the concentration of acetoacetate (the only ketone body present) remained low (<0.04mm) throughout the period of starvation. The concentration of plasma non-esterified fatty acids increased in bass, but decreased in dogfish. These changes are consistent with the predictions based on the enzyme-activity data. 4. Starvation did not change the activities of ketone-body-utilizing enzymes or that of phosphoenolpyruvate carboxykinase in heart and red skeletal muscles of both fish, but it decreased markedly the activity of phosphoenolpyruvate carboxykinase in white skeletal muscle of both fish. However, in the liver of the dogfish, starvation resulted in a twofold increase in the activities of 3-hydroxybutyrate dehydrogenase and acetoacetyl-CoA thiolase, whereas in bass liver it decreased the activity of acetoacetyl-CoA thiolase and increased that of 3-oxo acid CoA-transferase. The activity of phosphoenolpyruvate carboxykinase was increased twofold in the liver of bass, but was unchanged in that of the dogfish. 5. The difference in changes in concentrations of blood metabolites and enzyme activities in the two fish support the suggestion that, in starvation, ketone bodies, but not non-esterified fatty acids, are an important fuel for muscle in elasmobranchs, whereas non-esterified fatty acids, but not ketone bodies, are an important fuel in teleosts. The results are discussed in relation to the evolution of a discrete lipid-storing adipose tissue in teleosts and higher vertebrates.

Ketone-Body Concentrations in Liver and Blood after Limb Ischaemia in the Rat

1971 ◽  
Vol 40 (6) ◽  
pp. 463-477 ◽  
Author(s):  
R. N. Barton
Keyword(s):  
Fatty Acids ◽  
Hind Limb ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Regression Line ◽  
Early Response ◽  
Limb Ischaemia ◽  
Esterified Fatty Acids ◽  
Control Post ◽  
Body Concentration

1. The effect of a 4 h period of bilateral hind limb ischaemia on the concentrations of ketone bodies in blood and liver of post-absorptive and starved rats has been investigated. 2. The concentration of total ketone bodies in the blood did not change after injury in post-absorptive rats, but fell after injury in starved rats; the blood β-hydroxybutyrate/acetoacetate ratio fell after injury in both post-absorptive and starved rats. 3. Apart from a transient increase in fed rats, the hepatic β-hydroxybutyrate/acetoacetate ratio did not change after injury in post-absorptive or starved rats until the terminal stages, indicating adequate hepatic oxygenation during the early response to injury. 4. In control post-absorptive and starved rats the concentration of liver total ketone bodies was correlated with that of plasma non-esterified fatty acids; in post-absorptive rats the liver ketone body concentration rose after injury and was higher than would be predicted from the regression line for these controls, suggesting increased ketogenesis compatible with inhibition of complete oxidation of non-esterified fatty acids after injury. In contrast, in starved rats the liver total ketone-body concentration did not change after injury.

scholarly journals Activity of 3-oxo acid CoA-transferase, d-3-hydroxybutyrate dehydrogenase, hexokinase and carnitine palmitoyltransferase in the stomach and small and large intestine of the rat

1981 ◽  
Vol 200 (2) ◽  
pp. 349-355 ◽  
Author(s):  
P J Hanson ◽  
J M Carrington
Keyword(s):  
Fatty Acids ◽  
Gastrointestinal Tract ◽  
Glucose Utilization ◽  
Ketone Bodies ◽  
Carnitine Palmitoyltransferase ◽  
Maximal Rate ◽  
Anaerobic Conditions ◽  
Exogenous Fatty Acid ◽  
Coa Transferase ◽  
Small And Large Intestine

1. Activities of 3-oxo acid CoA-transferase, D-3-hydroxybutyrate dehydrogenase, hexokinase and carnitine palmitoyltransferase have been measured in the gastrointestinal tract. 2. Activity of 3-oxo acid CoA-transferase in the glandular mucosa of the stomach was as high as that in heart and kidney, and was 2--4 times greater than that in other regions of the gastrointestinal tract. It is suggested that metabolism of acetoacetate might support acid secretion on re-feeding after a period without food. 3. All regions of the gastrointestinal tract have the capacity to use ketone bodies, and it is likely that both muscle and mucosa will contribute to their utilization. 4. Activity of hexokinase was twice the rate of glucose utilization by the jejunum under anaerobic conditions. The maximal rate of glucose metabolism in the jejunum may not be substantially different from that in other regions of the gastrointestinal tract. 5. Starvation decreased the capacity for metabolism of glucose in several regions of the intestine. 6. Activities of carnitine palmitolytransferase in the stomach, jejunum and colon were similar, and about one-third of that in the liver. Activity in the jejunum was much higher than the apparent rate of oxidation of exogenous fatty acid. 7. The results do not suggest any large variation between tissues of the gastrointestinal tract in metabolism of glucose or fatty acids, whereas metabolism of ketone bodies may be more prominent in the stomach.

scholarly journals The course of ketosis and the activity of key enzymes of ketogenesis and ketone-body utilization during development of the postnatal rat

1971 ◽  
Vol 124 (1) ◽  
pp. 249-254 ◽  
Author(s):  
Elizabeth A. Lockwood ◽  
E. Bailey
Keyword(s):  
Specific Activity ◽  
Ketone Bodies ◽  
Mitochondrial Enzyme ◽  
Suckling Period ◽  
Stages Of Development ◽  
Development Activity ◽  
Blood Concentrations ◽  
Time Activity ◽  
Developmental Patterns ◽  
Coa Transferase

1. The highest blood concentrations of ketone bodies were found at 5 days of age, after which time the concentration fell to reach the adult value by 30 days of age. 2. Both mitochondrial and cytoplasmic hydroxymethylglutaryl-CoA synthase activities were detected, with highest activities being found in the mitochondria at all stages of development. Activity of the mitochondrial enzyme increases rapidly immediately after birth, showing a maximum at 15 days of age, thereafter falling to adult values. The cytoplasmic enzyme, on the other hand, increased steadily in activity after birth to reach a maximum at 40 days of age, after which time activity fell to adult values. 3. Both mitochondrial and cytoplasmic aceto-acetyl-CoA thiolase activities were detected, with the mitochondrial enzyme having considerably higher activities at all stages of development. The developmental patterns for both enzymes were very similar to those for the corresponding hydroxymethylglutaryl-CoA synthases. 4. The activity of heart acetoacetyl-CoA transferase remains constant from late foetal life until the end of the suckling period, after which time there is a gradual threefold increase in activity to reach the adult values. The activity of brain 3-oxo acid CoA-transferase increases steadily after birth, reaching a maximum at 30 days of age, thereafter decreasing to adult values, which are similar to foetal activities. Although at all stages of development the specific activity of the heart enzyme is higher than that of brain, the total enzymic capacity of the brain is higher than that of the heart during the suckling period.

scholarly journals Gluconeogenesis in the cow. The effects of a glucocorticoid on hepatic intermediary metabolism

1970 ◽  
Vol 116 (5) ◽  
pp. 865-874 ◽  
Author(s):  
G. D. Baird ◽  
R. J. Heitzman
Keyword(s):  
Blood Glucose ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Tyrosine Aminotransferase ◽  
Aspartate Transaminase ◽  
Blood Concentrations ◽  
Lactating Cows ◽  
Glycolytic Intermediates ◽  
Blood Glucose Concentrations ◽  
Parallel Measurements

1. The hepatic concentrations of the ketone bodies and of metabolites and activities of enzymes involved in gluconeogenesis were measured in healthy lactating and non-lactating cows 48h after administration of Voren, an ester of dexamethasone, and compared with those found in control animals given saline. Parallel measurements were also made of the blood concentrations of several of the metabolites. 2. Blood glucose concentrations were raised in the Voren-treated animals, whereas blood ketone body and free fatty acid concentrations were unaltered. Similarly there was no change in the hepatic concentrations of the ketone bodies. 3. Significant increases were found in the hepatic concentrations of citrate, 2-oxo-glutarate and malate in both groups of animals given Voren. 4. The hepatic concentrations of those glycolytic intermediates that were measured either decreased or did not change after Voren treatment. 5. The enzymes aspartate transaminase and fructose 1,6-diphosphatase were unchanged in activity after Voren administration, whereas phosphopyruvate carboxylase (EC 4.1.1.32) activity was depressed in the lactating group. However, glucose 6-phosphatase, tryptophan oxygenase and tyrosine aminotransferase increased in activity. 6. In several cases those hepatic metabolites that increased in concentration after Voren administration were present in lower concentration in normal lactating cows than in normal non-lactating cows. The same applied mutatis mutandis to those metabolites that were decreased by Voren. 7. These findings are discussed in relation to the use of glucocorticoids in the treatment of bovine ketosis.

P3476High-resolution respirometry reveals enhanced myocardial mitochondrial ketone oxidation after fasting and ventricular unloading

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Zweck ◽  
V Burkart ◽  
C Wessel ◽  
D Scheiber ◽  
K H M Leung ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Ex Vivo ◽  
Oxidative Capacity ◽  
Left Ventricular ◽  
University Hospital ◽  
Oxygen Flux ◽  
Protective Effects ◽  
Coa Transferase

Abstract Background Impairment of myocardial mitochondrial function is regarded as an established pathomechanism in heart failure. Enhanced oxidation of ketone bodies may potentially exert protective effects on myocardial function. High-resolution respirometry (HRR) resembles a gold-standard methodology to determine myocardial mitochondrial metabolism and oxidative function but has not been validated for ketone substrates yet. Purpose We hypothesized that (1) quantification of ketone body oxidative capacity (OC) in myocardium utilizing ex-vivo HRR is feasible and that (2) ketone-associated OC is elevated after fasting and under conditions of chronic mechanical ventricular unloading. Methods We established new HRR (Oxygraph-2k) protocols, measuring oxygen flux generated by oxidation of the ketone substrates beta-hydroxybutyrate (HBA) and acetoacetate (ACA). Ketone protocols were then applied to twelve C57BL/6 mice' (of which six were fasted for 16h) left ventricular and right liver lobe tissue, as well as to eleven terminal heart failure patients' left ventricular tissue, harvested at heart transplantation. Heart transplant recipients were subdivided into patients with left ventricular assist device prior to transplantation (LVAD group, n=6) or no unloading prior to transplantation (HTX group, n=5). Results In non-fasted rodent hearts, HBA yielded an OC of 25±4 pmol/(s*mg tissue) above basal respiration, when applied as sole substrate (21±11 pmol/(s*mg) in liver). ACA alone did not induce oxygen flux, but ACA+succinate yielded 229% higher oxygen flux than succinate alone in state III (146±32 vs 44±12 pmol/(s*mg); p=0.0003). When titrated after succinate, ACA increased OC by 93±25 pmol/(s*mg) (p=0.0003). In 16h-fasted rodent hearts, HBA-supported OC was 27% higher (41±3 vs 52±9 pmol/(s*mg); p=0.04), while OC with ACA+succinate was unchanged (p=0.60). In rodent liver, no oxygen flux was induced by ACA, reflecting absence of 3-oxoacid CoA-transferase. However, HBA-supported OC was 118% higher in fasted liver (37±13 vs 57±13 pmol/(s*mg); p=0.03). In humans, left ventricular unloading was not associated with altered myocardial OC for fatty acids and glycolytic substrates (standard protocol, p=0.13), but HBA-supported OC was 39% higher in the LVAD group compared to the HTX group (54±12 vs 39±9 pmol/(s*mg), p=0.04). Conclusion Quantification of ketone body OC with HRR is feasible in permeabilized myocardial fibers. Applying this novel method revealed increased HBA-supported myocardial mitochondrial respiration after fasting and chronic left ventricular unloading. These data support a concept of enhanced ketone oxidation following ventricular unloading in myocardial mitochondria. Our findings facilitate new studies on myocardial ketone turnover and the interaction of mitochondrial ketone metabolism with cardiac performance. Acknowledgement/Funding CRC 1116, Research commission of the University Hospital Düsseldorf

scholarly journals Effects of starvation on intermediary metabolism in the lactating cow. A comparison with metabolic changes occurring during bovine ketosis

1972 ◽  
Vol 128 (5) ◽  
pp. 1311-1318 ◽  
Author(s):  
G. D. Baird ◽  
R. J. Heitzman ◽  
K. G. Hibbitt
Keyword(s):  
Fatty Acids ◽  
Plasma Concentration ◽  
Dairy Cows ◽  
Blood Concentration ◽  
Ketone Bodies ◽  
Fat Metabolism ◽  
Metabolic Changes ◽  
Initial Increase ◽  
Blood Concentrations ◽  
Lactating Dairy Cows

1. The purpose of this study was to determine the nature of the metabolic changes associated with carbohydrate and fat metabolism that occurred in the blood and liver of lactating dairy cows during starvation for 6 days. 2. During starvation, the blood concentrations of the free fatty acids and ketone bodies increased, whereas that of citrate decreased. After an initial increase, the blood concentration of glucose subsequently declined as starvation progressed. Starvation caused a significant decrease in the plasma concentration of serine and a significant increase in that of leucine. 3. After 6 days of starvation the hepatic concentrations of oxaloacetate, citrate, phosphoenolpyruvate, 2-phosphoglycerate, 3-phosphoglycerate, glucose, glycogen, ATP and NAD+ had all decreased, as had the hepatic activities of phosphopyruvate carboxylase (EC 4.1.1.32) and pyruvate kinase (EC 2.7.1.40). 4. The above metabolic changes are similar to those previously found to occur in cows suffering from spontaneous ketosis (Baird et al., 1968; Baird & Heitzman, 1971). 5. Milk yield decreased progressively during starvation. 6. There were marked differences in the ability of individual animals to resist the onset of severe starvation ketosis.

scholarly journals Fatty acid metabolism in the perfused rat liver

1970 ◽  
Vol 119 (3) ◽  
pp. 525-533 ◽  
Author(s):  
H. A. Krebs ◽  
R. Hems
Keyword(s):  
Fatty Acids ◽  
Rat Liver ◽  
Ketone Body ◽  
Unsaturated Fatty Acids ◽  
Ketone Bodies ◽  
Saturated Fatty Acids ◽  
Perfused Rat Liver ◽  
Body Formation ◽  
Body Production ◽  
Chain Fatty Acids

1. The formation of acetoacetate, β-hydroxybutyrate and glucose was measured in the isolated perfused rat liver after addition of fatty acids. 2. The rates of ketone-body formation from ten fatty acids were approximately equal and independent of chain length (90–132μmol/h per g), with the exception of pentanoate, which reacted at one-third of this rate. The [β-hydroxybutyrate]/[acetoacetate] ratio in the perfusion medium was increased by long-chain fatty acids. 3. Glucose was formed from all odd-numbered fatty acids tested. 4. The rate of ketone-body formation in the livers of rats kept on a high-fat diet was up to 50% higher than in the livers of rats starved for 48h. In the livers of fat-fed rats almost all the O2 consumed was accounted for by the formation of ketone bodies. 5. The ketone-body concentration in the blood of fat-fed rats rose to 4–5mm and the [β-hydroxybutyrate]/[acetoacetate] ratio rose to 11.5. 6. When the activity of the microsomal mixed-function oxidase system, which can bring about ω-oxidation of fatty acids, was induced by treatment of the rat with phenobarbitone, there was no change in the ketone-body production from fatty acids, nor was there a production of glucose from even-numbered fatty acids. The latter would be expected if ω-oxidation occurred. Thus ω-oxidation did not play a significant role in the metabolism of fatty acids. 7. Arachidonate was almost quantitatively converted into ketone bodies and yielded no glucose, demonstrating that gluconeogenesis from poly-unsaturated fatty acids with an even number of carbon atoms does not occur. 8. The rates of ketogenesis from unsaturated fatty acids (sorbate, undecylenate, crotonate, vinylacetate) were similar to those from the corresponding saturated fatty acids. 9. Addition of oleate together with shorter-chain fatty acids gave only a slightly higher rate of ketone-body formation than oleate alone. 10. Glucose, lactate, fructose, glycerol and other known antiketogenic substances strongly inhibited endogenous ketogenesis but had no effects on the rate of ketone-body formation in the presence of 2mm-oleate. Thus the concentrations of free fatty acids and of other oxidizable substances in the liver are key factors determining the rate of ketogenesis.

scholarly journals The metabolism of circulating non-esterified fatty acids by the whole animal, hind-limb muscle and uterus of pregnant ewes

1983 ◽  
Vol 49 (1) ◽  
pp. 129-143 ◽  
Author(s):  
D. W. Pethick ◽  
D. B. Lindsay ◽  
P. J. Barker ◽  
A. J. Northrop
Keyword(s):  
Fatty Acids ◽  
Hind Limb ◽  
Ketone Bodies ◽  
Gravid Uterus ◽  
Limb Muscle ◽  
Entry Rate ◽  
Esterified Fatty Acids ◽  
Arterial Concentration ◽  
Pregnant Sheep ◽  
Hind Limb Muscle

1. The over-all and regional metabolism of non-esterified fatty acids (NEFA) was studied using a combination of isotopic and arteriovenous-difference techniques.2. There was a common linear relationship, whether stearic, palmitic or oleic acids were used as tracer, between the arterial NEFA concentration and the rates of entry and oxidation.3. Assuming that the tracer used reflected the metabolism of all the NEFA, the total entry rate in fed and fasted pregnant ewes was (mean±SE) 0·44±0·02 and 0·55±0·07 mmol/h per kg body-weight respectively. Oxidation of NEFA contributed (mean±SE) 34±5 and 58±7% to the respiratory carbon dioxide in fed and fasted animals, this accounting for (mean±SE) 46±6 and 59±3% of the respective entry rates.4. Hind-limb muscle both utilized and produced NEFA. The mean gross fractional extraction (calculated from isotopic uptake) was (mean±SE) 9±1%. Gross utilization of any NEFA and appearance of 14CO2 across the muscle were linearly related to the arterial concentration of tracer fatty acid, irrespective of whether this was oleate or stearate. The amount of 14CO2 appearing was consistent with (mean±SE) 54±8% of the CO2 produced by the hind-limb being derived from NEFA oxidation.5. Infused NEFA were partly converted to ketone bodies. Uptake and oxidation in the hind-limb of ketones formed in the liver could account for approximately 20% of the 14CO2 apparently produced in muscle from NEFA. Correction for this reduces the proportion of CO2 derived from NEFA to 43%. There was some indication that ketones were also produced from NEFA in the hind-limb.6. NEFA were not a significant energy source for the gravid uterus.7. An over-all view of energy sources for the whole animal and for hind-limb muscle in normal and fasted pregnant sheep was presented.

scholarly journals Relationship between plasma and muscle concentrations of ketone bodies and free fatty acids in fed, starved and alloxan-diabetic states

1973 ◽  
Vol 134 (2) ◽  
pp. 499-506 ◽  
Author(s):  
Oliver E. Owen ◽  
Helene Markus ◽  
Stuart Sarshik ◽  
Maria Mozzoli
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Free Fatty Acids ◽  
Plasma Glucose ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Water Concentration ◽  
Diabetic Rats ◽  
Muscle Membrane

1. Concentrations of ketone bodies, free fatty acids and chloride in fed, 24–120h-starved and alloxan-diabetic rats were determined in plasma and striated muscle. Plasma glucose concentrations were also measured in these groups of animals. 2. Intracellular metabolite concentrations were calculated by using chloride as an endogenous marker of extracellular space. 3. The mean intracellular ketone-body concentrations (±s.e.m.) were 0.17±0.02, 0.76±0.11 and 2.82±0.50μmol/ml of water in fed, 48h-starved and alloxan-diabetic rats, respectively. Mean (intracellular water concentration)/(plasma water concentration) ratios were 0.47, 0.30 and 0.32 in fed, 48h-starved and alloxan-diabetic rats respectively. The relationship between ketone-body concentrations in the plasma and intracellular compartments appeared to follow an asymptotic pattern. 4. Only intracellular 3-hydroxybutyrate concentrations rose during starvation whereas concentrations of both 3-hydroxybutyrate and acetoacetate were elevated in the alloxan-diabetic state. 5. During starvation plasma glucose concentrations were lowest at 48h, and increased with further starvation. 6. There was no significant difference in the muscle intracellular free fatty acid concentrations of fed, starved and alloxan-diabetic rats. Mean free fatty acid intramuscular concentrations (±s.e.m.) were 0.81±0.08, 0.98±0.21 and 0.91±0.10μmol/ml in fed, 48h-starved and alloxan-diabetic states. 7. The intracellular ketosis of starvation and the stability of free fatty acid intracellular concentrations suggests that neither muscle membrane permeability nor concentrations of free fatty acids per se are major factors in limiting ketone-body oxidation in these states.

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