Enzymes Of Ketone Body Metabolism Research Articles

Metabolic organization of the spotted ratfish,Hydrolagus colliei (Holocephali: Chimaeriformes): insight into the evolution of energy metabolism in the chondrichthyan fishes

The metabolic organization of a holocephalan, the spotted ratfish (Hydrolagus colliei), was assessed using measurements of key enzymes of several metabolic pathways in four tissues and plasma concentrations of free amino acids (FAA) and non-esterified fatty acids (NEFA) to ascertain if the Holocephali differ metabolically from the Elasmobranchii since these groups diverged ca. 400 Mya. Activities of carnitine palmitoyl transferase indicate that fatty acid oxidation occurs in liver and kidney but not in heart or white muscle. This result mirrors the well-established absence of lipid oxidation in elasmobranch muscle, and more recent studies showing that elasmobranch kidney possesses a capacity for lipid oxidation. High activities in oxidative tissues of enzymes of ketone body metabolism, including D-beta-hydroxybutyrate dehydrogenase, indicate that, like elasmobranchs, ketone bodies are of central importance in spotted ratfish. Like many carnivorous fishes, enzyme activities demonstrate that amino acids are metabolically important, although the concentration of plasma FAA was relatively low. NEFA concentrations are lower than in teleosts, but higher than in most elasmobranchs and similar to that in some "primitive" ray-finned fishes. NEFA composition is comparable to other marine temperate fishes, including high levels of n-6 and especially n-3 polyunsaturated fatty acids. The metabolic organization of the spotted ratfish is similar to that of elasmobranchs: a reduced capacity for lipid oxidation in muscle, lower plasma NEFA levels, and an emphasis on ketone bodies as oxidative fuel. This metabolic strategy was likely present in the common chondrichthyan ancestor, and may be similar to the ancestral metabolic state of fishes.

Brain uptake and metabolism of ketone bodies in animal models

As a consequence of the high fat content of maternal milk, the brain metabolism of the suckling rat represents a model of naturally occurring ketosis. During the period of lactation, the rate of uptake and metabolism of the two ketone bodies, β-hydroxybutyrate and acetoacetate is high. The ketone bodies enter the brain via monocarboxylate transporters whose expression and activity is much higher in the brain of the suckling than the mature rat. β-Hydroxybutyrate and acetoacetate taken up by the brain are efficiently used as substrates for energy metabolism, and for amino acid and lipid biosynthesis, two pathways that are important for this period of active brain growth. Ketone bodies can represent about 30–70% of the total energy metabolism balance of the immature rat brain. The active metabolism of ketone bodies in the immature brain is related to the high activity of the enzymes of ketone body metabolism. Thus, the use of ketone bodies by the immature rodent brain serves to spare glucose for metabolic pathways that cannot be fulfilled by ketones such as the pentose phosphate pathway mainly. The latter pathway leads to the biosynthesis of ribose mandatory for DNA synthesis and NADPH which is not formed during ketone body metabolism and is a key cofactor in lipid biosynthesis. Finally, ketone bodies by serving mainly biosynthetic purposes spare glucose for the emergence of various functions such as audition, vision as well as more integrated and adapted behaviors whose appearance during brain maturation seems to critically relate upon active glucose supply and specific regional increased use.

Novel aspects of the activities and subcellular distribution of enzymes of ketone body metabolism in the liver and kidney of the goldfish, Carassius auratus

The metabolic organization of ketone body metabolism of liver and kidney of the goldfish Carassius auratus was assessed by measuring maximal activities, subcellular distribution, and stereoisomer preference of ketone body enzymes. These determinations indicate that the organization of ketone body metabolism in liver and kidney of goldfish differs from that of mammals in some respects. All the enzymes of ketone body metabolism were present in liver and kidney of goldfish, with the exception of hydroxymethylglutaryl-CoA (HMG-CoA) synthetase, which was not detected in liver. Two forms of β-hydroxybutyrate dehydrogenase (βHBDH) with different stereospecificity for β-hydroxybutyrate (D- and L-β-hydroxybutyrate) were detectable in liver and kidney. All of the ketone body enzymes measured in liver were mainly in the mitochondrial fraction, with the exception of D- and L-βHBDH, which were cytosolic. In kidney, HMG-CoA synthase, together with HMG-CoA lyase and acetoacetyl CoA thiolase (AcoAT), were found mainly in the mitochondrial fraction. L-βHBDH was mainly cytosolic in kidney, but by contrast with liver, D-βHBDH was mainly found in the mitochondria, and SKT was distributed in both the mitochondrial and cytosolic compartments. J. Exp. Zool. 286:434–439, 2000. © 2000 Wiley-Liss, Inc.

Novel aspects of the activities and subcellular distribution of enzymes of ketone body metabolism in the liver and kidney of the goldfish,Carassius auratus

The metabolic organization of ketone body metabolism of liver and kidney of the goldfish Carassius auratus was assessed by measuring maximal activities, subcellular distribution, and stereoisomer preference of ketone body enzymes. These determinations indicate that the organization of ketone body metabolism in liver and kidney of goldfish differs from that of mammals in some respects. All the enzymes of ketone body metabolism were present in liver and kidney of goldfish, with the exception of hydroxymethylglutaryl-CoA (HMG-CoA) synthetase, which was not detected in liver. Two forms of beta-hydroxybutyrate dehydrogenase (betaHBDH) with different stereospecificity for beta-hydroxybutyrate (D- and L-beta-hydroxybutyrate) were detectable in liver and kidney. All of the ketone body enzymes measured in liver were mainly in the mitochondrial fraction, with the exception of D- and L-betaHBDH, which were cytosolic. In kidney, HMG-CoA synthase, together with HMG-CoA lyase and acetoacetyl CoA thiolase (AcoAT), were found mainly in the mitochondrial fraction. L-betaHBDH was mainly cytosolic in kidney, but by contrast with liver, D-betaHBDH was mainly found in the mitochondria, and SKT was distributed in both the mitochondrial and cytosolic compartments. J. Exp. Zool. 286:434-439, 2000.

Importance of Ketone Bodies to the Intermediary Metabolism of the Terrestrial Snail, Archachatina ventricosa: Evidence from Enzyme Activities

The maximal activities of enzymes of ketone body metabolism and selected enzymes of other pathways of intermediary metabolism were measured in heart, hepatopancreas, kidney, mantle and foot muscle of the terrestrial pulmonate gastropod Archachatina ventricosa. These measurements indicate the importance of ketone bodies in the energy metabolism of several aerobic tissues in this snail. Three enzymes that catalyze steps in the pathway to convert ketone bodies to acetyl-CoA are particularly high in the ventricle, which suggests that β-hydroxybutyrate and acetoacetate are important energy substrates in this tissue. The organization of ketone body metabolism in A. ventricosa tissues appears to differ from that of mammals in that no hydroxymethylglutaryl-CoA synthase activity is detected in any tissue. However, ketogenesis may occur through other pathways, including the readily reversible reactions of the ketolytic pathway. Our data suggest that the kidney may be a ketogenic tissue in these snails. comp. biochem. physiol. 117B;2:197–201, 1997.

Subcellular organization of intermediary metabolism in the hepatopancreas of the terrestrial snail, Cepaea nemoralis: A cytosolic β‐hydroxybutyrate dehydrogenase

The subcellular distributions of key enzymes of the tricarboxylic acid cycle, electron transport chain, ketone body, amino acid, and carbohydrate metabolism were studied in the hepatopancreas of the terrestrial snail Cepaea nemoralis. The presence of mitochondrial carnitine octanoyl transferase, carnitine palmitoyl transferase, and 3-hydroxyacyl-CoA dehydrogenase indicate an active lipid catabolic pathway in this tissue. Activities of enzymes of ketone body metabolism are similar in magnitude to those of carbohydrate metabolism, suggesting an important metabolic role for ketone bodies in C. nemoralis. Two enzymes that, in mammals, catalyze the synthesis of ketone bodies, hydroxymethylglutaryl-CoA synthase and hydroxymethylglutaryl-CoA lyase, are not detectable in Cepaea hepatopancreas. The activity of 3-oxoacid-CoA transferase and a portion of acetoacetyl-CoA thiolase activity are found in the mitochondria. β-hydroxybutyrate dehydrogenase is a cytosolic enzyme in this tissue, and preferentially oxidizes the L-isomer of β-hydroxybutyrate. A portion of glutamate dehydrogenase activity is also cytosolic. The subcellular organization distribution of enzymes of intermediary metabolism in Cepaea hepatopancreas suggests adaptation to periodic anoxia. © 1996 Wiley-Liss, Inc.

Subcellular organization of intermediary metabolism in the hepatopancreas of the terrestrial snail,Cepaea nemoralis: A cytosolic β-hydroxybutyrate dehydrogenase

The subcellular distributions of key enzymes of the tricarboxylic acid cycle, electron transport chain, ketone body, amino acid, and carbohydrate metabolism were studied in the hepatopancreas of the terrestrial snail Cepaea nemoralis. The presence of mitochondrial carnitine octanoyl transferase, carnitine palmitoyl transferase, and 3-hydroxyacyl-CoA dehydrogenase indicate an active lipid catabolic pathway in this tissue. Activities of enzymes of ketone body metabolism are similar in magnitude to those of carbohydrate metabolism, suggesting an important metabolic role for ketone bodies in C. nemoralis. Two enzymes that, in mammals, catalyze the synthesis of ketone bodies, hydroxymethylglutaryl-CoA synthase and hydroxymethylglutaryl-CoA lyase, are not detectable in Cepaea hepatopancreas. The activity of 3-oxoacid-CoA transferase and a portion of acetoacetyl-CoA thiolase activity are found in the mitochondria. β-hydroxybutyrate dehydrogenase is a cytosolic enzyme in this tissue, and preferentially oxidizes the L-isomer of β-hydroxybutyrate. A portion of glutamate dehydrogenase activity is also cytosolic. The subcellular organization distribution of enzymes of intermediary metabolism in Cepaea hepatopancreas suggests adaptation to periodic anoxia. © 1996 Wiley-Liss, Inc.

Differential action of thyroid hormones on the activity of certain enzymes in rat kidney and brain

In rat kidney several mitochondrial and soluble enzyme activities are stimulated by thyroid hormones and the mitochondrial membrane fluidity is also increased. However, the ketone metabolism enzyme activities of D-3-hydroxybutyrate dehydrogenase and of 3-oxoacid CoA-transferase are not significantly affected by the hyperthyroid state and the ketone body concentration is not greatly changed. Therefore, in hyperthyroid rats the response of the kidney, as far as the ketone bodies and their metabolizing enzymes are concerned, is at variance with that of the liver and the heart. In the brain of young rats, age 8-9 weeks, the activities of the enzymes of ketone body metabolism and those responsible for other metabolic pathways are not influenced by the hyperthyroid state. In these animals, however, the activities of two enzymes, NAD-isocitrate dehydrogenase and pyruvate kinase, are still stimulated by 28 and 41%, respectively. This can be probably related to the higher energy requirement for definitive brain maturation in young hyperthyroid rats.

Investigations on the ketone body metabolism inBiomphalaria glabrata: Influence of starvation and of infection withSchistosoma mansoni

Ketone body concentration, 3-hydroxybutyrate oxidation rates in vivo and in vitro in the hepatopancreas and the activities of enzymes of ketone body metabolism in mitochondrial samples from different tissues were investigated in normal specimens ofBiomphalaria glabrata and under conditions of starvation and of infection withSchistosoma mansoni.

Activities of the enzymes of ketone body metabolism in the developing chick

1.1. The concentration of ketone bodies in the blood of the developing chick prior to and just after hatching were higher than those found in the adult.2.2. The activities of 3-oxo acid-CoA transferase and acetoacetyl-CoA thiolase in the heart, leg and pectoral muscle before and after hatching were higher than those of the adult. The activity of 3-hydroxybutyrate dehydrogenase increased constantly during incubation and after hatching in all three muscle tissues.3.3. In the liver the activities of the enzymes of ketone body synthesis increased during incubation and after hatching.4.4. It is suggested that the liver could provide fuel to the extrahepatic tissues of the developing chick and ketone bodies could contribute as fuel for oxidation in the skeletal muscle of the newly hatched bird.

Activities of enzymes of ketone body metabolism in liver and muscle tissues of suckling rabbits

1. 1. The concentration of ketone bodies in blood of suckling rabbits during the first 6 days following birth was higher than that found in the adult. 2. 2. In the liver the activities of the enzymes of ketone body synthesis were higher than in the adult during the same period. 3. 3. In the heart and leg muscle the activities of the enzymes of ketone body utilization were lower than those found in the adult. 4. 4. It is suggested that the capacity of muscles of the developing rabbit to utilize ketone bodies is not greater than that of the adult and ketone bodies produced by the liver could contribute as fuel for oxidation and/or synthesis to the brain of the newborn rabbit.

Renal ketone body metabolism. Distribution of 3-oxoacid CoA-transferase and 3-hydroxybutyrate dehydrogenase along the mouse nephron.

Two enzymes of ketone body metabolism, 3-oxoacid CoA-transferase and 3-hydroxybutyrate dehydrogenase were measured with ultramicromethods to map their activities along single, dissected segments of mouse nephron. 3-Oxoacid CoA-transferase activity was assayed with a radiochemical procedure by separating [14C]succinyl-CoA, formed in the presence of acetoacetyl-CoA from [1,4-14C]succinate. This procedure, when compared to the spectrophotometric method, resulted in similar activities in mouse organ homogenates. 3-Hydroxybutyrate dehydrogenase activity was determined with sufficient sensitivity by using NADH-dependent luciferase. The dehydrogenase exhibited only 5% of the activity of the 3-oxoacid CoA-transferase when measured in mouse kidney cortex homogenates. Both enzymes were found to be present in all nephron structures studies. The specific activity related to tubular protein, which was determined in parallel in all segments dissected, exhibited a typical distribution pattern along the nephron. Both enzymes roughly paralleled each other along the structures of the distal nephron. They exhibited high activities in the thick ascending limb of Henle's loop and the distal convoluted tubule, but decreased to nearly 20% in the segments of the collecting tubule. In the proximal convoluted and straight tubule 3-oxoacid CoA-transferase activity was almost equal. In contrast, 3-hydroxybutyrate dehydrogenase increased by a factor of 5 from the convoluted to the straight portion. This heterogeneity along the proximal tubule remained when pure D-hydroxybutyrate was used as substrate, but was not found when rat or rabbit nephron segments were analysed. Lowest activities of enzymes were recovered from glomeruli and thin descending limbs of Henle's loop. The results obtained allow for the conclusion that 3-hydroxybutyrate and acetoacetate can be metabolized in all structures of the mouse nephron with different capacities in various segments. With the exception of the relatively low activity of 3-hydroxybutyrate dehydrogenase in the proximal convoluted tubule, the distribution pattern mirrors the distribution of mitochondria along the rat nephron. The results point to the possible role of ketone bodies as energy fuels for nephron segments performing active transport processes.

Effect of thyroid hormones on the 3-oxo acid CoA-transferase activity in rat brain during development.

The changes in the developmental pattern of 3-oxo acid CoA-transferase activity in the brain of hypothyroid rats and the effect of triiodothyronine on this enzyme activity have been investigated. Hypothyroid rats showed lower activity than controls during the suckling period. However, higher enzyme levels were found in treated rats after weaning in contrast to control animals. The results suggest that thyroid hormones promote the development of enzymes of ketone-body metabolism in the brain.

Fatty Acid and Ketone Body Metabolism in the Rat: Response to Diet and Exercise

This study was designed to measure the response of key enzymes of ketone body metabolism in heart, skeletal muscle, and liver to diet and exercise, two conditions known to influence ketone body utilization. A 3 (diet: control, high fat, or high carbohydrate) X 2 (kill condition: rested or exhausted) X 2 (training: trained or untrained) factorial design was used to estimate main experimental effects as well as identify significant interactions of the variables. Physical training (treadmill running) was associated with a doubling of the activity of skeletal muscle 3-oxoacid CoA transferase, a key enzyme in extrahepatic ketone body utilization. The activity of the rate-limiting enzyme of liver ketone body production, hydroxymethylglutaryl CoA synthetase (HMG CoA synthetase), was not greatly influenced by training or exhuastive exercise indicating that the metabolic control of the ketosis of exercise may more likely be a function of the supply of fatty acids to the liver rather than the activity of HMG CoA synthetase. Feeding a high fat diet, on the other hand, significantly increased the activity of liver HMG CoA synthetase, indicating that the ketosis of fat feeding may be of a different nature than that of exercise. The results of this study indicate that physical training is associated with biochemical adaptations in ketone body metabolism as well as fatty acid oxidation, and that trained individuals are metabolically better endowed to benefit from the ketosis of exercise than untrained individuals.

THE INTERMEDIARY METABOLISM OF FATTY ACIDS

ArticlesTHE INTERMEDIARY METABOLISM OF FATTY ACIDSWilliam C. StadieWilliam C. StadiePublished Online:01 Jul 1945https://doi.org/10.1152/physrev.1945.25.3.395MoreSectionsPDF (7 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited BySynthesis of Lipides22 November 2006Activities of the enzymes of ketone body metabolism in the developing chickComparative Biochemistry and Physiology Part B: Comparative Biochemistry, Vol. 81, No. 3On the biochemical etiology of ketosisLife Sciences, Vol. 3, No. 6 More from this issue > Volume 25Issue 3July 1945Pages 395-441 https://doi.org/10.1152/physrev.1945.25.3.395History Published online 1 July 1945 Published in print 1 July 1945 Metrics