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Exogenous ketone
JMwangi98: Posted new article onto Wikipedia.
Exogenous ketones are a class of [[ketone bodies]] that are ingested through nutritional supplements. This class of ketone bodies refers to the three water-soluble [[Ketone|ketones]] ([[Acetoacetic acid|acetoacetate]], [[Beta-Hydroxybutyric acid|ß-hydroxybutyrate [ß-HB]]], and [[acetone]])<ref name=":0">Ketosource. Exogenous ketones: What they are, benefits of use and how they work. Ketosource, ketogenic diets, ketosis & ketones Web site. <nowiki>https://ift.tt/2Jri8yz>. Accessed 3/28/, 2018.</ref>. These ketone bodies are produced by interactions between macronutrient availability such as low glucose and high free fatty acids or hormone signaling such as low [[insulin]] and high [[glucagon]]/[[cortisol]]<ref name=":1">Stubbs BJ, Cox PJ, Stirling M, et al. On the metabolism of exogenous ketones in humans. ''Frontiers in Physiology''. 2017;8. <nowiki>https://ift.tt/2GH1hWW>. Accessed Mar 28, 2018. doi: 10.3389/fphys.2017.00848.</ref>. Under physiological conditions, ketone concentrations can increase due to starvation, ketogenic diets, or prolonged exercise, leading to ketosis<ref name=":1" />. However, with the introduction of exogenous ketone supplements, it is possible to provide a user with an instant supply of ketones even if the body is not within a state of [[ketosis]] before ingestion<ref name=":0" />.
Most supplements rely on ß-hydroxybutyrate as the source of exogenous ketone bodies. ß-HB is the most common exogenous ketone body because of its efficient energy conversion and ease of synthesis<ref name=":0" />. In the body, ß-HB can be converted to acetoacetic acid. It is this acetoacetic acid that will enter the energy pathway using beta-ketothialase, becoming two [[Acetyl-CoA]] molecules<ref name=":0" />. The Acetyl CoA is then able to enter the [[Citric acid cycle|Krebs cycle]] in order to generate ATP. The remaining ß-HB molecules that aren't synthesized into acetoacetic acid are then converted to acetone through the acetoacetate decarboxylase waste mechanism<ref name=":0" />.
== Structure ==
[[File:Acetoacetic_acid.png|link=https://en.wikipedia.org/wiki/File:Acetoacetic_acid.png|none|thumb|178x178px|Acetoacetic acid]]
Acetoacetate is produced in the [[Mitochondrion|mitochondria]] of liver cells by the addition of an acetyl group from acetyl CoA. This creates 3-hydroxy-3-methylgluteryl CoA which loses an acetyl group, becoming acetoacetate <ref name=":2">Lubert Stryer (1981). ''Biochemistry'' (2nd ed.). p. 393</ref>.
[[File:Beta-Hydroxybutyric_acid-2D-skeletal.svg|link=https://en.wikipedia.org/wiki/File:Beta-Hydroxybutyric_acid-2D-skeletal.svg|none|thumb|180x180px|Beta-Hydroxybutyrate]]
ß-hydroxybutyrate is also synthesized within liver cells; this is accomplished through the metabolism of fatty acids. Through a series of reactions, acetoacetate is first produced; and it is this acetoacetate that is reduced into ß-hydroxybutyrate, catalyzed by the ß-hydroxybutyrate dehydrogenase enzyme <ref name=":3">Kesl SL, Poff AM, Ward NP, et al. Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in sprague-dawley rats. ''Nutrition & metabolism''. 2016;13(9):9. <nowiki>https://ift.tt/2JqyvM7>. doi: 10.1186/s12986-016-0069-y.</ref><ref name=":2" />. Although, ß-hydroxybutyrate is technically not a ketone due to the structure of the molecule (OH- attached to carbonyl group makes this an acid), ß-HB acts like a ketone, providing the body with energy in the absence of [[glucose]] <ref name=":0" />.
[[File:Acetone-2D-skeletal.svg|link=https://en.wikipedia.org/wiki/File:Acetone-2D-skeletal.svg|none|thumb|131x131px|Acetone]]
Acetone is an [[organic compound]] with the formula (CH3)2CO and is one of the simplest and smallest ketones. It is synthesized from the breakdown of acetoacetate in ketotic individuals within the liver <ref name=":2" />.
== Types ==
==== Ketone Salts ====
Ketone salts are natural compounds, such as ß-HB, that are mixed with sodium, potassium, or calcium to improve absorption <ref name=":0" />.
[[File:ß-Hydroxybutyrate_salt.png|link=https://en.wikipedia.org/wiki/File:%C3%9F-Hydroxybutyrate_salt.png|none|thumb|ß-Hydroxybutyrate salt]]
==== Ketone Esters ====
Ketone esters are synthetic compounds that link an alcohol group to a ketone body. This ketone body is then metabolized to a ketone within the liver <ref name=":0" />.
[[File:BHB_Ester.png|link=https://en.wikipedia.org/wiki/File:BHB_Ester.png|none|thumb|269x269px|ß-Hydroxybutryate ester]]
== Effects ==
The consumption of ketone bodies results in several effects, ranging from reduced glucose utilization in peripheral tissues, anti-lipolytic effects on adipose tissue, and reduced [[proteolysis]] in skeletal muscle <ref name=":3" /><ref name=":4">Evans M, Cogan KE, Egan B. Metabolism of ketone bodies during exercise and training: Physiological basis for exogenous supplementation. ''The Journal of Physiology''. 2017;595(9):2857-2871. <nowiki>https://ift.tt/2GDC5k5>. doi: 10.1113/JP273185.</ref>. In addition to this, ketone bodies serve as signaling molecules that regulate gene expression and adaptive responses <ref name=":4" />. When exogenous ketone bodies are ingested, acute and nutritional ketosis is produced <ref name=":3" /><ref name=":4" />. This nutritional ketosis alters the metabolic response to exercise and enhances exercise performance <ref name=":4" />.
==== Blood ====
In human blood, ketone ester and ketone salt consumption delivers a >50% higher plasma concentration of D-ß-Hydroxybutyrate, an [[Protein isoform|isoform]] of regular ß-HB <ref name=":1" />. In terms of efficacy, the blood D-ßHB concentrations are higher when using ketone esters instead of ketone salts (KE = 2.8±0.2 mM; KS = 1.0±mM) <ref name=":1" />. This is due to the fact that the KE supplement contains >99% of the D-ßHB-isoform while the KS supplement contains ~50% of the L-ßHB-isoform, which is metabolized much slower than the D-ßHB-isoform <ref name=":1" />. Also, ketone salt supplements slightly raise the blood pH level. This is mainly due to the [[Conjugate acid|conjugate base]] action of ßHB (ßHB-) which fully dissociates within the blood; this mildly raises the blood and urine pH which is further increased as the kidneys excrete the excess [[Ion|cations]] (Na+, Ca+, K+)<ref name=":1" />. Ketone esters reduce the blood pH because KE [[hydrolysis]] proves ß-HB with butanediol. These two undergoe a hepatic metabolism, forming a keto-acid <ref name=":1" />.
==== Hormones ====
Exogenous ketones lower blood glucose concentrations <ref name=":1" /><ref name=":3" /><ref name=":5">Stubbs BJ, Cox PJ, Evans RD, Cyranka M, Clarke K, de Wet H. A ketone ester drink lowers human ghrelin and appetite. ''Obesity''. 2018;26(2):269-273. <nowiki>https://ift.tt/2JnReYJ>. doi: 10.1002/oby.22051.</ref>. Although [[carbohydrate]] stores are plentiful, ketones lower the blood glucose because they limit [[Gluconeogenesis|hepatic gluconeogenesis]] and increase peripheral glucose intake <ref name=":1" />. They have also been known to reduce hunger and the desire to eat. This is shown by the decreased levels of the hunger hormone, [[ghrelin]] <ref name=":5" />. In addition, it has been surmised that exogenous ketones may stimulate [[insulin]] secretion. Following exposure to exogenous ketones, small amounts of secreted insulin have been reported in animals. However, because insulin has also been shown to increase in subjects who took an exogenous ketone supplement and dextrose drink, in addition to those who only took the exogenous supplement, more research remains to be seen on the effects of ketone supplements on insulin <ref name=":1" />.
== See Also ==
[[Ketone]]
[[Ketone bodies]]
[[Acetoacetic acid|Acetoacetate]]
[[Beta-Hydroxybutyric acid|ß-hydroxybutyrate [ß-HB]]]
[[Acetone]]
== References ==
<references />
Most supplements rely on ß-hydroxybutyrate as the source of exogenous ketone bodies. ß-HB is the most common exogenous ketone body because of its efficient energy conversion and ease of synthesis<ref name=":0" />. In the body, ß-HB can be converted to acetoacetic acid. It is this acetoacetic acid that will enter the energy pathway using beta-ketothialase, becoming two [[Acetyl-CoA]] molecules<ref name=":0" />. The Acetyl CoA is then able to enter the [[Citric acid cycle|Krebs cycle]] in order to generate ATP. The remaining ß-HB molecules that aren't synthesized into acetoacetic acid are then converted to acetone through the acetoacetate decarboxylase waste mechanism<ref name=":0" />.
== Structure ==
[[File:Acetoacetic_acid.png|link=https://en.wikipedia.org/wiki/File:Acetoacetic_acid.png|none|thumb|178x178px|Acetoacetic acid]]
Acetoacetate is produced in the [[Mitochondrion|mitochondria]] of liver cells by the addition of an acetyl group from acetyl CoA. This creates 3-hydroxy-3-methylgluteryl CoA which loses an acetyl group, becoming acetoacetate <ref name=":2">Lubert Stryer (1981). ''Biochemistry'' (2nd ed.). p. 393</ref>.
[[File:Beta-Hydroxybutyric_acid-2D-skeletal.svg|link=https://en.wikipedia.org/wiki/File:Beta-Hydroxybutyric_acid-2D-skeletal.svg|none|thumb|180x180px|Beta-Hydroxybutyrate]]
ß-hydroxybutyrate is also synthesized within liver cells; this is accomplished through the metabolism of fatty acids. Through a series of reactions, acetoacetate is first produced; and it is this acetoacetate that is reduced into ß-hydroxybutyrate, catalyzed by the ß-hydroxybutyrate dehydrogenase enzyme <ref name=":3">Kesl SL, Poff AM, Ward NP, et al. Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in sprague-dawley rats. ''Nutrition & metabolism''. 2016;13(9):9. <nowiki>https://ift.tt/2JqyvM7>. doi: 10.1186/s12986-016-0069-y.</ref><ref name=":2" />. Although, ß-hydroxybutyrate is technically not a ketone due to the structure of the molecule (OH- attached to carbonyl group makes this an acid), ß-HB acts like a ketone, providing the body with energy in the absence of [[glucose]] <ref name=":0" />.
[[File:Acetone-2D-skeletal.svg|link=https://en.wikipedia.org/wiki/File:Acetone-2D-skeletal.svg|none|thumb|131x131px|Acetone]]
Acetone is an [[organic compound]] with the formula (CH3)2CO and is one of the simplest and smallest ketones. It is synthesized from the breakdown of acetoacetate in ketotic individuals within the liver <ref name=":2" />.
== Types ==
==== Ketone Salts ====
Ketone salts are natural compounds, such as ß-HB, that are mixed with sodium, potassium, or calcium to improve absorption <ref name=":0" />.
[[File:ß-Hydroxybutyrate_salt.png|link=https://en.wikipedia.org/wiki/File:%C3%9F-Hydroxybutyrate_salt.png|none|thumb|ß-Hydroxybutyrate salt]]
==== Ketone Esters ====
Ketone esters are synthetic compounds that link an alcohol group to a ketone body. This ketone body is then metabolized to a ketone within the liver <ref name=":0" />.
[[File:BHB_Ester.png|link=https://en.wikipedia.org/wiki/File:BHB_Ester.png|none|thumb|269x269px|ß-Hydroxybutryate ester]]
== Effects ==
The consumption of ketone bodies results in several effects, ranging from reduced glucose utilization in peripheral tissues, anti-lipolytic effects on adipose tissue, and reduced [[proteolysis]] in skeletal muscle <ref name=":3" /><ref name=":4">Evans M, Cogan KE, Egan B. Metabolism of ketone bodies during exercise and training: Physiological basis for exogenous supplementation. ''The Journal of Physiology''. 2017;595(9):2857-2871. <nowiki>https://ift.tt/2GDC5k5>. doi: 10.1113/JP273185.</ref>. In addition to this, ketone bodies serve as signaling molecules that regulate gene expression and adaptive responses <ref name=":4" />. When exogenous ketone bodies are ingested, acute and nutritional ketosis is produced <ref name=":3" /><ref name=":4" />. This nutritional ketosis alters the metabolic response to exercise and enhances exercise performance <ref name=":4" />.
==== Blood ====
In human blood, ketone ester and ketone salt consumption delivers a >50% higher plasma concentration of D-ß-Hydroxybutyrate, an [[Protein isoform|isoform]] of regular ß-HB <ref name=":1" />. In terms of efficacy, the blood D-ßHB concentrations are higher when using ketone esters instead of ketone salts (KE = 2.8±0.2 mM; KS = 1.0±mM) <ref name=":1" />. This is due to the fact that the KE supplement contains >99% of the D-ßHB-isoform while the KS supplement contains ~50% of the L-ßHB-isoform, which is metabolized much slower than the D-ßHB-isoform <ref name=":1" />. Also, ketone salt supplements slightly raise the blood pH level. This is mainly due to the [[Conjugate acid|conjugate base]] action of ßHB (ßHB-) which fully dissociates within the blood; this mildly raises the blood and urine pH which is further increased as the kidneys excrete the excess [[Ion|cations]] (Na+, Ca+, K+)<ref name=":1" />. Ketone esters reduce the blood pH because KE [[hydrolysis]] proves ß-HB with butanediol. These two undergoe a hepatic metabolism, forming a keto-acid <ref name=":1" />.
==== Hormones ====
Exogenous ketones lower blood glucose concentrations <ref name=":1" /><ref name=":3" /><ref name=":5">Stubbs BJ, Cox PJ, Evans RD, Cyranka M, Clarke K, de Wet H. A ketone ester drink lowers human ghrelin and appetite. ''Obesity''. 2018;26(2):269-273. <nowiki>https://ift.tt/2JnReYJ>. doi: 10.1002/oby.22051.</ref>. Although [[carbohydrate]] stores are plentiful, ketones lower the blood glucose because they limit [[Gluconeogenesis|hepatic gluconeogenesis]] and increase peripheral glucose intake <ref name=":1" />. They have also been known to reduce hunger and the desire to eat. This is shown by the decreased levels of the hunger hormone, [[ghrelin]] <ref name=":5" />. In addition, it has been surmised that exogenous ketones may stimulate [[insulin]] secretion. Following exposure to exogenous ketones, small amounts of secreted insulin have been reported in animals. However, because insulin has also been shown to increase in subjects who took an exogenous ketone supplement and dextrose drink, in addition to those who only took the exogenous supplement, more research remains to be seen on the effects of ketone supplements on insulin <ref name=":1" />.
== See Also ==
[[Ketone]]
[[Ketone bodies]]
[[Acetoacetic acid|Acetoacetate]]
[[Beta-Hydroxybutyric acid|ß-hydroxybutyrate [ß-HB]]]
[[Acetone]]
== References ==
<references />
April 07, 2018 at 02:10AM
