WordNet

invest with or as with a body; give body to (同)personify
the external structure of a vehicle; "the body of the car was badly rusted"
the main mass of a thing
a natural object consisting of a dead animal or person; "they found the body in the lake" (同)dead body
the entire structure of an organism (an animal, plant, or human being); "he felt as if his whole body were on fire" (同)organic structure, physical structure
a collection of particulars considered as a system; "a body of law"; "a body of doctrine"; "a body of precedents"
a group of persons associated by some common tie or occupation and regarded as an entity; "the whole body filed out of the auditorium"; "the student body"; "administrative body"
an individual 3-dimensional object that has mass and that is distinguishable from other objects; "heavenly body"
the central message of a communication; "the body of the message was short"
any of a class of organic compounds having a carbonyl group linked to a carbon atom in each of two hydrocarbon radicals

PrepTutorEJDIC

〈C〉『身体』,肉体 / 〈C〉(人・動物の)『胴体』 / 〈C〉)物の)『主要部』,本体《+『of』+『名』》 / 〈C〉(…の)『団体』,群れ:(…のたくさんの)集まり《+『of』+『名』》 / 〈C〉物体,…体 / 〈U〉実質;(酒・味などの)こく / 〈C〉《話》人
《英話》人;(特に)男

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/05/13 21:36:30」(JST)

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Chemical structures of the three ketone bodies: acetone (top), acetoacetic acid (middle), and beta-hydroxybutyric acid (bottom).

Ketone bodies are three water-soluble, biochemicals that are produced by the liver from fatty acids during periods of low food intake (fasting) or carbohydrate restriction for cells of the body to use as energy instead of glucose. Two of the three are used as a source of energy in the heart and brain while the third (acetone) is a degradation breakdown product of acetoacetic acid. Radioactive tracing of acetone determines that between 2% and 30% is excreted from the body. Ketone bodies are picked up by cells and converted back into acetyl-CoA which then enters the citric acid cycle and electron transport chain for energy. In the brain ketone bodies are also used to make Acetyl CoA into long chain fatty acids because long chain fatty acids cannot pass through the blood brain barrier. The liver breaks down protein to produce glucose during starvation for the very few glucose obligate cells that cannot use ketone bodies.^[1]^[2] In the brain, ketone bodies are a vital source of energy during fasting or strenuous exercise.^[3] Although termed "bodies", they are molecules, not particles.

The three endogenous ketone bodies are acetone, acetoacetic acid, and beta-hydroxybutyric acid.^[4] Other ketone bodies such as beta-ketopentanoate and beta-hydroxypentanoate may be created as a result of the metabolism of synthetic triglycerides such as triheptanoin.

Uses in the heart, brain and liver

Ketone bodies can be used for energy. Ketone bodies are transported from the liver to other tissues, where acetoacetate and beta-hydroxybutyrate can be reconverted to acetyl-CoA to produce energy, via the citric acid cycle. Ketone bodies cannot be used by the liver for energy. Acetone in low concentrations is taken up by the liver and undergoes detoxification through the methylglyoxal pathway which ends with lactate. Acetone in high concentrations due to prolonged fasting or a ketogenic diet is absorbed by cells other than those in the liver and enters a different pathway via 1,2-propanediol. Though the pathway follows a different series of steps requiring ATP, can be turned into pyruvate.^[5]

The heart preferentially utilizes fatty acids for energy under normal physiologic conditions. However, under ketotic conditions, the heart can effectively utilize ketone bodies for energy.^[6]

The brain gets a portion of its energy from ketone bodies when glucose is less available (e.g., during fasting, strenuous exercise, low carbohydrate, ketogenic diet and in neonates). In the event of low blood glucose, most other tissues have additional energy sources besides ketone bodies (such as fatty acids), but the brain has an obligatory requirement for some glucose. After the diet has been changed to lower blood glucose for 3 days, the brain gets 25% of its energy from ketone bodies.^[7] After about 4 days, this goes up to 70%^{[citation needed]} (during the initial stages the brain does not burn ketones, since they are an important substrate for lipid synthesis in the brain). Furthermore, ketones produced from omega-3 fatty acids may reduce cognitive deterioration in old age.^[8]

Production

Acetyl-CoA

Ketone bodies are produced from acetyl-CoA (see ketogenesis) mainly in the mitochondrial matrix of hepatocytes when carbohydrates are so scarce that energy must be obtained from breaking down fatty acids. Because of the high level of acetyl CoA present in the cell, the pyruvate dehydrogenase complex is inhibited, whereas pyruvate carboxylase becomes activated. High levels of ATP and NADH inhibit the enzyme isocitrate dehydrogenase in the TCA cycle (tricarboxylic acid cycle or the Krebs cycle) and as a result cause an increase in the concentration of malate (due to the equilibrium between itself and oxaloacetate). The malate then leaves the mitochondrion and undergoes gluconeogenesis. The elevated level of NADH and ATP result from β-oxidation of fatty acids.^[9] Unable to be used in the citric acid cycle, the excess acetyl-CoA is therefore rerouted to ketogenesis. Such a state in humans is referred to as the fasted state.

Acetone is produced by spontaneous decarboxylation of acetoacetate, meaning this ketone body will break down in five hours^{[citation needed]} if it is not used for energy and be removed as waste, or converted to Pyruvate.^[5] This "use it or lose it" factor may contribute to the weight loss found in ketogenic diets. Acetone cannot be converted back to acetyl-CoA, so it is excreted in the urine, or (as a consequence of its high vapor pressure) exhaled unless first converted to Pyruvate. Acetone is responsible for the characteristic "Sweet & fruity" odor of the breath of persons in ketoacidosis.^[10]

Ketosis and ketoacidosis

In normal individuals, there is a constant production of ketone bodies by the liver and their utilization by extrahepatic tissues. The concentration of ketone bodies in blood is maintained around 1 mg/dl. Their excretion in urine is very low and undetectable by routine urine tests (Rothera's test).

When the rate of synthesis of ketone bodies exceeds the rate of utilization, their concentration in blood increases; this is known as ketonemia. This is followed by ketonuria – excretion of ketone bodies in urine. The overall picture of ketonemia and ketonuria is commonly referred as ketosis. Smell of acetone in breath is a common feature in ketosis.

When a type 1 diabetic suffers a biological stress event (sepsis, heart attack, infection) or fails to administer enough insulin they may suffer the pathological condition ketoacidosis. Liver cells increase metabolism of fatty acids into ketones in an attempt to supply energy to peripheral cells which are unable to transport glucose in the absence of insulin. The resulting very high levels of blood glucose and ketone bodies lower the pH of the blood and trigger the kidneys to attempt to excrete the glucose and ketones. Osmotic diuresis of glucose will cause further removal of water and electrolytes from the blood resulting in potentially fatal dehydration, tachycardia and hypotension.

Individuals who follow a low-carbohydrate diet will also develop ketosis, sometimes called nutritional ketosis, but the level of ketone body concentrations are on the order of 0.5-5 mM whereas the pathological ketoacidosis is 15-25 mM.

As the mainstream diet of diabetic patients is so high in carbohydrate, ketosis is rarely seen without ketoacidosis resulting from low serum insulin levels. Many medical practitioners mistake well regulated nutritional ketosis for pathological ketoacidosis.^[11]

Impact upon pH

Both acetoacetic acid and beta-hydroxybutyric acid are acidic, and, if levels of these ketone bodies are too high, the pH of the blood drops, resulting in ketoacidosis, a complication of untreated Type I diabetes, and sometimes in end stage Type II (see diabetic ketoacidosis).

References

^ Martha H. Stipanuk, Marie A. Caudill (2013). Biochemical, Physiological, and Molecular Aspects of Human Nutrition. pp. 378–381, 449–456. ISBN 978-1-4377-0959-9.
^ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC371996/pdf/jcinvest00676-0075.pdf
^ Mary K. Campbell, Shawn O. Farrell (2006). Biochemistry (5th ed.). Cengage Learning. p. 579. ISBN 0-534-40521-5.
^ Lori Laffel (1999). "Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes". Diabetes/Metabolism Research and Reviews 15 (6): 412–426. doi:10.1002/(SICI)1520-7560(199911/12)15:6<412::AID-DMRR72>3.0.CO;2-8. PMID 10634967.
^ ^a ^b http://www.epa.gov/iris/toxreviews/0128tr.pdf
^ Kodde IF, van der Stok J, Smolenski RT, de Jong JW (January 2007). "Metabolic and genetic regulation of cardiac energy substrate preference". Comp. Biochem. Physiol., Part a Mol. Integr. Physiol. 146 (1): 26–39. doi:10.1016/j.cbpa.2006.09.014. PMID 17081788.
^ Hasselbalch, SG; Knudsen, GM; Jakobsen, J; Hageman, LP; Holm, S; Paulson, OB (1994). "Brain metabolism during short-term starvation in humans.". Journal of cerebral blood flow and metabolism 14 (1): 125–31. doi:10.1038/jcbfm.1994.17. PMID 8263048.
^ Freemantle, E.; Vandal, M. N.; Tremblay-Mercier, J.; Tremblay, S. B.; Blachère, J. C.; Bégin, M. E.; Thomas Brenna, J.; Windust, A.; Cunnane, S. C. (2006). "Omega-3 fatty acids, energy substrates, and brain function during aging". Prostaglandins, Leukotrienes and Essential Fatty Acids 75 (3): 213. doi:10.1016/j.plefa.2006.05.011. edit
^ Baynes medical biochemistry
^ American Diabetes Association-Ketoacidosis
^ Thomas M. Devlin. (2010). Textbook of Biochemistry with Clinical Correlations. (7th Ed.) John Wiley & Sons. p. 699. ISBN 978-0-47-028173-4

External links

emerg/135 at eMedicine - Diabetic Ketoacidosis
Fat metabolism at unisanet.unisa.edu.au
NHS Direct Online Health Encyclopaedia, Ketosis
BioCarta Pathways Formation of Ketone Bodies
Ketone Bodies at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 空腹時ケトアシドーシスおよびアルコール性ケトアシドーシス fasting ketosis and alcoholic ketoacidosis
2. 成人における糖尿病性ケトアシドーシスおよび高浸透圧性高血糖状態の臨床的特徴および診断 clinical features and diagnosis of diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults
3. 幼児および小児における低血糖症の病因 etiology of hypoglycemia in infants and children
4. インスリン作用 insulin action
5. 乳児および小児における低血糖に対するアプローチ approach to hypoglycemia in infants and children

English Journal

Induced hyperketonemia affects the mammary immune response during lipopolysaccharide challenge in dairy cows.

Zarrin M1, Wellnitz O2, van Dorland HA2, Bruckmaier RM3.Author information 1Veterinary Physiology, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, 3001 Bern, Switzerland; Department of Animal Science, Agriculture Faculty, Yasouj University, Student Street, 75918-74831, Yasouj, Iran; Graduate School for Cellular and Biomedical Sciences, University of Bern, Freiestrasse 1, 3012 Bern, Switzerland.2Veterinary Physiology, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, 3001 Bern, Switzerland.3Veterinary Physiology, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, 3001 Bern, Switzerland. Electronic address: rupert.bruckmaier@vetsuisse.unibe.ch.AbstractMetabolic adaptations during negative energy and nutrient balance in dairy cows are thought to cause impaired immune function and hence increased risk of infectious diseases, including mastitis. Characteristic adaptations mostly occurring in early lactation are an elevation of plasma ketone bodies and free fatty acids (nonesterified fatty acids, NEFA) and diminished glucose concentration. The aim of this study was to investigate effects of elevated plasma β-hydroxybutyrate (BHBA) at simultaneously even or positive energy balance and thus normal plasma NEFA and glucose on factors related to the immune system in liver and mammary gland of dairy cows. In addition, we investigated the effect of elevated plasma BHBA and intramammary lipopolysaccharide (LPS) challenge on the mammary immune response. Thirteen dairy cows were infused either with BHBA (HyperB, n=5) to induce hyperketonemia (1.7mmol/L) or with a 0.9% saline solution (NaCl, n=8) for 56h. Two udder quarters were injected with 200μg of LPS after 48h of infusion. Rectal temperature (RT) and somatic cell counts (SCC) were measured before, at 48h after the start of infusions, and hourly during the LPS challenge. The mRNA abundance of factors related to the immune system was measured in hepatic and mammary tissue biopsies 1 wk before and 48h after the start of the infusion, and additionally in mammary tissue at 56h of infusion (8h after LPS administration). At 48h of infusion in HyperB, the mRNA abundance of serum amyloid A (SAA) in the mammary gland was increased and that of haptoglobin (Hp) tended to be increased. Rectal temperature, SCC, and mRNA abundance of candidate genes in the liver were not affected by the BHBA infusion until 48h. During the following LPS challenge, RT and SCC increased in both groups. However, SCC increased less in HyperB than in NaCl. Quarters infused with LPS showed a more pronounced increase of mRNA abundance of IL-8 and IL-10 in HyperB than in NaCl. The results demonstrate that an increase of plasma BHBA upregulates acute phase proteins in the mammary gland. In response to intramammary LPS challenge, elevated BHBA diminishes the influx of leukocytes from blood into milk, perhaps by via modified cytokine synthesis. Results indicate that increased ketone body plasma concentrations may play a crucial role in the higher mastitis susceptibility in early lactation.
Journal of dairy science.J Dairy Sci.2014 Jan;97(1):330-9. doi: 10.3168/jds.2013-7222. Epub 2013 Nov 13.
Metabolic adaptations during negative energy and nutrient balance in dairy cows are thought to cause impaired immune function and hence increased risk of infectious diseases, including mastitis. Characteristic adaptations mostly occurring in early lactation are an elevation of plasma ketone bodies a
PMID 24239080

METABOLOMICS REVEALS METABOLITE CHANGES IN ACUTE PULMONARY EMBOLISM.

Bujak R, García-Álvarez A, Rupérez FJ, Nuño-Ayala M, García A, Ruiz-Cabello J, Fuster V, Ibáñez B, Barbas C.AbstractPulmonary embolism (PE) is a common cardiovascular emergency which can lead to pulmonary hypertension (PH) and right ventricular failure as a consequence of pulmonary arterial bed occlusion. The diagnosis of PE is challenging due to non-specific clinical presentation what results in relatively high mortality. Moreover, the pathological factors associated with PE are poorly understood. Metabolomics can provide with new highlights which can help in the understanding of the processes and even propose biomarkers for its diagnosis. In order to obtain more information about PE and PH, acute PE was induced in large white pigs and plasma was obtained before and after induction of PE. Metabolic fingerprints from plasma were obtained with LC-QTOF-MS (positive and negative ionization) and GC-Q-MS. Data pretreatment and statistical analysis (uni- and multivariate) was performed in order to compare metabolic fingerprints and to select the metabolites that showed higher loading for the classification (28 from LC and 19 from GC). The metabolites found differentially distributed among groups are mainly related to energy imbalance in hypoxic conditions, such as glycolysis-derived metabolites, ketone bodies, and TCA cycle intermediates, as well as a group of lipidic mediators that could be involved in the transduction of the signals to the cells such as sphingolipids and lysophospholipids, among others. Results presented in this report reveal that combination of LC-MS- and GC-MS-based metabolomics could be a powerful tool for diagnosis and understanding pathophysiological processes due to acute PE.
Journal of proteome research.J Proteome Res.2013 Dec 24. [Epub ahead of print]
Pulmonary embolism (PE) is a common cardiovascular emergency which can lead to pulmonary hypertension (PH) and right ventricular failure as a consequence of pulmonary arterial bed occlusion. The diagnosis of PE is challenging due to non-specific clinical presentation what results in relatively high
PMID 24367941

Japanese Journal

β-Hydroxybutyrate increases the pilocarpine-induced seizure threshold in young mice

YUM Mi-Sun,KO Tae-Sung,KIM Dong Wook
Brain & development 34(3), 181-184, 2012-03-01
NAID 10031050013

Age-related effects of fasting on ketone body production during lipolysis in rats

HIGASHINO MATSUI Yuriko,SHIRATO Ken,SUZUKI Yuko,KAWASHIMA Yu,SOMEYA Yui,SATO Shogo,SHIRAISHI Akira,JINDE Manabu,MATSUMOTO Akiko,IDENO Hisashi,TACHIYASHIKI Kaoru,IMAIZUMI Kazuhiko
Environmental health and preventive medicine 17(2), 157-163, 2012-03-01
NAID 10030543036