View source for Carbohydrate metabolism

{{Short description|Biochemical process in living organisms}}

'''Carbohydrate metabolism''' is the whole of the [[biochemistry|biochemical]] processes responsible for the metabolic [[anabolism|formation]], [[catabolism|breakdown]], and interconversion of [[carbohydrate]]s in [[life|living]] [[organism]]s.

Carbohydrates are central to many essential [[metabolic pathway]]s.<ref name=":3">{{Cite journal |last=Maughan |first=Ron |title=Carbohydrate metabolism |journal=Surgery (Oxford) |volume=27 |issue=1 |pages=6–10 |doi=10.1016/j.mpsur.2008.12.002 |year=2009}}</ref> [[Plant]]s synthesize carbohydrates from [[carbon dioxide]] and [[water]] through [[photosynthesis]], allowing them to store energy absorbed from sunlight internally.<ref name=":0">{{Cite book |title=Lehninger principles of biochemistry |last=Nelson |first=David Lee |date=2013 |publisher=W.H. Freeman and Company |others=Cox, Michael M., Lehninger, Albert L. |isbn=978-1-4292-3414-6 |edition=6th |location=New York |oclc=824794893}}</ref> When [[animal]]s and [[fungi]] consume plants, they use [[cellular respiration]] to break down these stored carbohydrates to make energy available to cells.<ref name=":0" /> Both animals and plants temporarily store the released energy in the form of high-energy molecules, such as [[adenosine triphosphate]] (ATP), for use in various cellular processes.<ref name=":1">{{Cite book |last=Sanders |first=L. M. |pages=643–650 |doi=10.1016/b978-0-12-384947-2.00114-8 |title=Encyclopedia of Food and Health |year=2016 |isbn=978-0-12-384953-3 |chapter=Carbohydrate: Digestion, Absorption and Metabolism}}</ref>

While carbohydrates are essential to human biological processes, ''consuming'' them is not essential for humans. There are healthy human populations that do not consume carbohydrates.<ref>{{cite web|url=https://www.discovermagazine.com/health/the-inuit-paradox?|title=The Inuit Paradox}}</ref>
In humans, carbohydrates are available directly from consumption, from carbohydrate storage, or by conversion from fat components including fatty acids<ref name="pmid21814506">{{cite journal | vauthors = Kaleta C, de Figueiredo LF, Werner S, Guthke R, Ristow M, Schuster S | title = In silico evidence for gluconeogenesis from fatty acids in humans | journal = PLOS Computational Biology | volume = 7 | issue = 7 | article-number = e1002116 | date = July 2011 | pmid = 21814506 | pmc = 3140964 | doi = 10.1371/journal.pcbi.1002116 | bibcode = 2011PLSCB...7E2116K | doi-access = free }}</ref> that are either stored or consumed directly.

==Metabolic pathways==
[[File:Carbohydrate Metabolism.png|thumb|660x660px|Overview of connections between metabolic processes.]]

=== Glycolysis ===
[[Glycolysis]] is the process of breaking down a glucose molecule into two [[pyruvate]] molecules, while storing energy released during this process as [[adenosine triphosphate]] (ATP) and [[nicotinamide adenine dinucleotide]] (NADH).<ref name=":0" /> Nearly all organisms that break down glucose utilize glycolysis.<ref name=":0" /> Glucose regulation and product use are the primary categories in which these pathways differ between organisms.<ref name=":0" /> In some tissues and organisms, glycolysis is the sole method of energy production.<ref name=":0" /> This pathway is common to both anaerobic and aerobic respiration.<ref name=":3" />

Glycolysis consists of ten steps, split into two phases.<ref name=":0" /> During the first phase, it requires the breakdown of two ATP molecules.<ref name=":3" /> During the second phase, chemical energy from the intermediates is transferred into ATP and NADH.<ref name=":0" /> The breakdown of one molecule of glucose results in two molecules of pyruvate, which can be further oxidized to access more energy in later processes.<ref name=":3" />

Glycolysis can be regulated at different steps of the process through feedback regulation. The step that is regulated the most is the third step. This regulation is to ensure that the body is not over-producing pyruvate molecules. The regulation also allows for the storage of glucose molecules into fatty acids.<ref name="khanacademy.org">"Regulation of Cellular Respiration (Article)." Khan Academy. www.khanacademy.org, https://www.khanacademy.org/science/biology/cellular-respiration-and-fermentation/variations-on-cellular-respiration/a/regulation-of-cellular-respiration.</ref> There are various enzymes that are used throughout glycolysis. The enzymes [[upregulate]], [[downregulate]], and [[feedback regulate]] the process.

[[File:Glycolysis skeletal diagram.png|thumb|660x660px|The Glycolysis pathway diagram illustrates the metabolic reactions that allow for the breakdown of glucose into pyruvate, often as preparation for further catabolic reactions.]]

=== Gluconeogenesis ===
[[Gluconeogenesis]] (GNG) is a [[metabolic pathway]] that results in the generation of [[glucose]] from certain non-[[carbohydrate]] carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms.<ref>{{cite book| first1 = David L | last1 = Nelson | first2 = Michael M | last2 = Cox | name-list-style = vanc |url=https://archive.org/details/lehningerprincip01lehn/page/724|title=Lehninger Principles of Biochemistry|publisher=Worth Publishers|year=2000|isbn=978-1-57259-153-0|location=USA|page=[https://archive.org/details/lehningerprincip01lehn/page/724 724]}}</ref> In vertebrates, gluconeogenesis occurs mainly in the [[liver]] and, to a lesser extent, in the [[renal cortex|cortex]] of the [[kidney]]s. It is one of two primary mechanisms – the other being degradation of [[glycogen]] ([[glycogenolysis]]) – used by humans and many other animals to maintain [[blood sugar level]]s, avoiding low levels ([[hypoglycemia]]).<ref>{{cite web|last=Silva|first=Pedro | name-list-style = vanc |title=The Chemical Logic Behind Gluconeogenesis|url=http://www2.ufp.pt/~pedros/bq/gng.htm|archive-url=https://web.archive.org/web/20090826043311/http://www2.ufp.pt/~pedros/bq/gng.htm|archive-date=August 26, 2009|access-date=September 8, 2009}}</ref> In [[ruminant]]s, because dietary carbohydrates tend to be metabolized by [[rumen]] organisms, gluconeogenesis occurs regardless of fasting, low-carbohydrate diets, exercise, etc.<ref name=Beitz2004>{{cite book | vauthors = Beitz DC | date = 2004 | chapter = Carbohydrate metabolism. | veditors = Reese WO | title = Dukes' Physiology of Domestic Animals | edition = 12th | publisher = Cornell Univ. Press | pages = 501–15 |isbn=978-0-8014-4238-4}}</ref>  In many other animals, the process occurs during periods of [[fasting]], [[starvation]], [[low-carbohydrate diet]]s, or intense [[exercise]].

In humans, substrates for gluconeogenesis may come from any non-carbohydrate sources that can be converted to pyruvate or intermediates of [[glycolysis]] (see figure). For the breakdown of [[protein]]s, these substrates include [[glucogenic amino acid]]s (although not [[ketogenic amino acid]]s); from breakdown of [[lipid]]s (such as [[triglyceride]]s), they include [[glycerol]], odd-chain fatty acids (although not even-chain fatty acids, see below); and from other parts of [[metabolism]] they include [[lactic acid|lactate]] from the [[Cori cycle]]. Under conditions of prolonged fasting, [[acetone]] derived from [[ketone bodies]] can also serve as a substrate, providing a pathway from fatty acids to glucose.<ref name="pmid21814506">{{cite journal | vauthors = Kaleta C, de Figueiredo LF, Werner S, Guthke R, Ristow M, Schuster S | title = In silico evidence for gluconeogenesis from fatty acids in humans | journal = PLOS Computational Biology | volume = 7 | issue = 7 | article-number = e1002116 | date = July 2011 | pmid = 21814506 | pmc = 3140964 | doi = 10.1371/journal.pcbi.1002116 | bibcode = 2011PLSCB...7E2116K | doi-access = free }}</ref> Although most gluconeogenesis occurs in the liver, the relative contribution of gluconeogenesis by the kidney is increased in diabetes and prolonged fasting.<ref name="pmid30370538">{{cite journal | vauthors = Swe MT, Pongchaidecha A, Chatsudthipong V, Chattipakorn N, Lungkaphin A | title = Molecular signaling mechanisms of renal gluconeogenesis in nondiabetic and diabetic conditions | journal = Journal of Cellular Physiology | volume = 234 | issue = 6 | pages = 8134–8151 | date = June 2019 | pmid = 30370538 | doi = 10.1002/jcp.27598 | s2cid = 53097552 }}</ref>

The gluconeogenesis pathway is highly [[endergonic]] until it is coupled to the hydrolysis of ATP or [[guanosine triphosphate]] (GTP), effectively making the process [[exergonic]]. For example, the pathway leading from [[pyruvate]] to [[glucose-6-phosphate]] requires 4 molecules of ATP and 2 molecules of GTP to proceed spontaneously. These ATPs are supplied from [[Fatty acid metabolism|fatty acid catabolism]] via [[beta oxidation]].<ref>{{Cite book|last=Rodwell|first=Victor | name-list-style = vanc |title=Harper's illustrated Biochemistry, 30th edition|publisher=McGraw Hill|year=2015|isbn=978-0-07-182537-5|location=USA|page=193}}</ref>

=== Glycogenolysis ===
[[Glycogenolysis]] refers to the breakdown of glycogen.<ref name=":5">{{Cite journal|last=Dashty|first=Monireh|title=A quick look at biochemistry: Carbohydrate metabolism|journal=Clinical Biochemistry|volume=46|issue=15|pages=1339–52|doi=10.1016/j.clinbiochem.2013.04.027|pmid=23680095|year=2013}}</ref> In the liver, muscles, and the kidney, this process occurs to provide glucose when necessary.<ref name=":5" /> A single glucose molecule is cleaved from a branch of glycogen, and is transformed into [[Glucose 1-phosphate|glucose-1-phosphate]] during this process.<ref name=":3" /> This molecule can then be converted to [[Glucose 6-phosphate|glucose-6-phosphate]], an [[Reaction intermediate|intermediate]] in the glycolysis pathway.<ref name=":3" />

Glucose-6-phosphate can then progress through glycolysis.<ref name=":3" /> Glycolysis only requires the input of one molecule of ATP when the glucose originates in glycogen.<ref name=":3" /> Alternatively, glucose-6-phosphate can be converted back into glucose in the liver and the kidneys, allowing it to raise blood glucose levels if necessary.<ref name=":0" />

[[Glucagon]] in the liver stimulates glycogenolysis when the blood glucose is lowered, known as hypoglycemia.<ref name=":5" /> The glycogen in the liver can function as a backup source of glucose between meals.<ref name=":0" /> Liver [[glycogen]] mainly serves the central nervous system. Adrenaline stimulates the breakdown of glycogen in the skeletal muscle during exercise.<ref name=":5" /> In the muscles, glycogen ensures a rapidly accessible energy source for movement.<ref name=":0" />

=== Glycogenesis ===
Glycogenesis refers to the process of synthesizing glycogen.<ref name=":5" /> In humans, glucose can be converted to glycogen via this process.<ref name=":0" /> Glycogen is a highly branched structure, consisting of the core protein [[Glycogenin]], surrounded by branches of glucose units, linked together.<ref name=":0" /><ref name=":5" />  The branching of glycogen increases its solubility, and allows for a higher number of glucose molecules to be accessible for breakdown at the same time.<ref name=":0" /> Glycogenesis occurs primarily in the liver, skeletal muscles, and kidney.<ref name=":0" /> The Glycogenesis pathway consumes energy, like most synthetic pathways, because an ATP and a UTP are consumed for each molecule of glucose introduced.<ref>{{Cite book|last1=Gropper|first1=Sareen S.|url=https://books.google.com/books?id=9-C5DQAAQBAJ&q=advanced+nutrition+and+human+metabolism+by+gropper|title=Advanced Nutrition and Human Metabolism|last2=Smith|first2=Jack L.|last3=Carr|first3=Timothy P.|date=2016-10-05|publisher=Cengage Learning|isbn=978-1-337-51421-7|language=en}}</ref>

=== Pentose phosphate pathway ===
The [[pentose phosphate pathway]] is an alternative method of oxidizing glucose.<ref name=":5" /> It occurs in the liver, [[adipose tissue]], [[adrenal cortex]], [[testis]], [[mammary glands]], [[phagocytes]], and [[red blood cells]].<ref name=":5" /> It produces products that are used in other cell processes, while reducing NADP to NADPH.<ref name=":5" /><ref name=":7">{{Cite journal|date=2017-01-15|title=The regulation of the pentose phosphate pathway: Remember Krebs|journal=Archives of Biochemistry and Biophysics|volume=614|pages=50–52|doi=10.1016/j.abb.2016.12.012|pmid=28041936|issn=0003-9861 | last1 = Ramos-Martinez | first1 = Juan Ignacio }}</ref> This pathway is regulated through changes in the activity of glucose-6-phosphate dehydrogenase.<ref name=":7" />

=== Fructose metabolism ===
Fructose must undergo certain extra steps in order to enter the glycolysis pathway.<ref name=":0" /> Enzymes located in certain tissues can add a phosphate group to fructose.<ref name=":5" /> This phosphorylation creates fructose-6-phosphate, an intermediate in the glycolysis pathway that can be broken down directly in those tissues.<ref name=":5" /> This pathway occurs in the muscles, adipose tissue, and kidney.<ref name=":5" /> In the liver, enzymes produce fructose-1-phosphate, which enters the glycolysis pathway and is later cleaved into glyceraldehyde and dihydroxyacetone phosphate.<ref name=":0" />

=== Galactose metabolism ===
Lactose, or milk sugar, consists of one molecule of glucose and one molecule of galactose.<ref name=":5" /> After separation from glucose, galactose travels to the liver for conversion to glucose.<ref name=":5" /> Galactokinase uses one molecule of ATP to phosphorylate galactose.<ref name=":0" /> The phosphorylated galactose is then converted to glucose-1-phosphate, and then eventually glucose-6-phosphate, which can be broken down in glycolysis.<ref name=":0" />

==Energy production==
Many steps of carbohydrate metabolism allow the cells to access energy and store it more transiently in ATP.<ref name=":6">{{Cite book |title=Biochemistry Free for All |last1=Ahern |first1=Kevin |last2=Rajagopal |first2=Indira |last3=Tan |first3=Taralyn |publisher=Oregon State University |year=2017 }}</ref> The cofactors NAD<sup>+</sup> and FAD are sometimes reduced during this process to form NADH and FADH<sub>2</sub>, which drive the creation of ATP in other processes.<ref name=":6" /> A molecule of NADH can produce 1.5–2.5 molecules of ATP, whereas a molecule of FADH<sub>2</sub> yields 1.5 molecules of ATP.<ref name="energetics">[http://pharmaxchange.info/press/2013/10/energetics-of-cellular-respiration-glucose-metabolism/ Energetics of Cellular Respiration (Glucose Metabolism)].</ref>
{| class="wikitable"
|+Energy produced during metabolism of one glucose molecule
!Pathway
!ATP input
!ATP output
!Net ATP
!NADH output
!FADH<sub>2</sub> output
!ATP final yield
|-
|Glycolysis (aerobic)
|2
|4
|2
|2
|0
|5-7
|-
|Citric-acid cycle
|0
|2
|2
|6
|2
|17-25
|}
Typically, the complete breakdown of one molecule of glucose by aerobic respiration (i.e. involving glycolysis, the [[citric-acid cycle]] and [[oxidative phosphorylation]], the last providing the most energy) is usually about 30–32 molecules of ATP.<ref name="energetics" /> Oxidation of one gram of carbohydrate yields approximately 4 kcal of [[Chemical energy|energy]].<ref name=":1" />

==Carbohydrate Consumption==

Humans can consume a variety of carbohydrates, [[digestion]] breaks down complex carbohydrates into simple [[monomer]]s ([[monosaccharide]]s): [[glucose]], [[fructose]], [[mannose]] and [[galactose]]. After [[resorption (digestion)|resorption]] in the [[human digestive system|gut]], the monosaccharides are transported, through the [[portal vein]], to the liver, where all non-glucose monosacharids (fructose, galactose) are transformed into glucose as well.<ref name=":2">{{Cite book |title=Guyton and Hall Textbook of Medical Physiology E-Book |last=Hall |first=John E. |publisher=Elsevier Health Sciences |year=2015 |isbn=978-0-323-38930-3 |edition=13 }}</ref> Glucose ([[blood sugar]]) is distributed to cells in the tissues, where it is broken down via [[cellular respiration]], or stored as [[glycogen]].<ref name=":1" /><ref name=":2" /> In cellular (aerobic) respiration, glucose and [[oxygen]] are metabolized to release energy, with carbon dioxide and [[water]] as endproducts.<ref name=":0" /><ref name=":2" />


==Hormonal regulation==
Glucoregulation is the maintenance of steady levels of glucose in the body.

[[Hormone]]s released from the [[pancreas]] regulate the overall metabolism of glucose.<ref name=":4">{{Cite book|last=Lebovitz|first=Harold E.|pages=737–51|doi=10.1016/b978-0-323-18907-1.00042-1|title=Endocrinology: Adult and Pediatric|year=2016|isbn=978-0-323-18907-1|chapter=Hyperglycemia Secondary to Nondiabetic Conditions and Therapies}}</ref> [[Insulin]] and [[glucagon]] are the primary hormones involved in maintaining a steady level of glucose in the blood, and the release of each is controlled by the amount of nutrients currently available.<ref name=":4" /> The amount of insulin released in the blood and sensitivity of the cells to the insulin both determine the amount of glucose that cells break down.<ref name=":2" /> Increased levels of glucagon activates the enzymes that catalyze glycogenolysis, and inhibits the enzymes that catalyze glycogenesis.<ref name=":6" /> Conversely, glycogenesis is enhanced and glycogenolysis inhibited when there are high levels of insulin in the blood.<ref name=":6" />

The level of circulatory glucose (known informally as "blood sugar"), as well as the detection of nutrients in the Duodenum is the most important factor determining the amount of glucagon or insulin produced. The release of glucagon is precipitated by low levels of blood glucose, whereas high levels of blood glucose stimulates cells to produce insulin. Because the level of circulatory glucose is largely determined by the intake of dietary carbohydrates, diet controls major aspects of metabolism via insulin.<ref>{{Cite journal|last=Brockman|first=R P|date=March 1978|title=Roles of glucagon and insulin in the regulation of metabolism in ruminants. A review.|journal=The Canadian Veterinary Journal|volume=19|issue=3|pages=55–62|issn=0008-5286|pmc=1789349|pmid=647618}}</ref> In humans, insulin is made by beta cells in the [[pancreas]], fat is stored in [[adipose tissue]] cells, and glycogen is both stored and released as needed by liver cells. Regardless of insulin levels, no glucose is released to the blood from internal glycogen stores from muscle cells.

== Carbohydrates as storage ==
Carbohydrates are typically stored as long polymers of glucose molecules with [[glycosidic bond]]s for structural support (e.g. [[chitin]], [[cellulose]]) or for energy storage (e.g. [[glycogen]], [[starch]]). However, the strong affinity of most carbohydrates for water makes storage of large quantities of carbohydrates inefficient due to the large molecular weight of the solvated water-carbohydrate complex. In most organisms, excess carbohydrates are regularly catabolised to form [[acetyl-CoA]], which is a feed stock for the [[fatty acid synthesis]] pathway; [[fatty acids]], [[triglycerides]], and other [[lipids]] are commonly used for long-term energy storage. The hydrophobic character of lipids makes them a much more compact form of energy storage than hydrophilic carbohydrates. [[Gluconeogenesis]] permits glucose to be synthesized from various sources, including lipids.<ref>G Cooper, ''The Cell'', American Society of Microbiology, p. 72</ref>

In some animals (such as [[termite]]s)<ref>{{cite journal |last=Watanabe |first=Hirofumi |author2=Hiroaki Noda |author3=Gaku Tokuda |author4=Nathan Lo |date=23 July 1998 |title=A cellulase gene of termite origin |journal=Nature |volume=394 |issue=6691 |pages=330–31 |bibcode=1998Natur.394..330W |doi=10.1038/28527 |pmid=9690469 |s2cid=4384555}}</ref> and some microorganisms (such as [[protist]]s and [[bacteria]]), cellulose can be disassembled during digestion and absorbed as glucose.<ref>{{Cite journal|last=Coleman|first=Geoffrey|date=8 February 1978|title=The Metabolism of Cellulose, Glucose, and Starch by the Rumen Ciliate Protozoon Eudiplodinium Magii|journal=Journal of General Microbiology|volume=107|issue=2|pages=359–66|doi=10.1099/00221287-107-2-359|doi-access=free}}</ref>

==Human diseases==
* [[Diabetes mellitus]]
* [[Lactose intolerance]]
* [[Fructose malabsorption]]
* [[Galactosemia]]
* [[Glycogen storage disease]]

== See also ==
{{Portal|Biology}}

* [[Inborn errors of carbohydrate metabolism]] 
* [[Hitting the wall]] (glycogen depletion) 
* [[Second wind]] (increased ATP from fatty acids after glycogen depletion)

==References==
{{reflist}}

==External links==
* {{MeshName|Carbohydrate+metabolism}}
* [https://web.archive.org/web/20070604033140/http://www.bbc.co.uk/schools/gcsebitesize/biology/humansasorganisms/6homeostasisrev4.shtml BBC - GCSE Bitesize - Biology | Humans | Glucoregulation]
* [https://web.archive.org/web/20110721110608/http://www.medbio.info/Horn/Sugars4Kids/ Sugar4Kids]

{{Carbohydrate metabolism}}
{{MetabolismMap}}
{{Gluconeogenesis}}
{{Glycogenolysis}}
{{Fructose and galactose metabolism}}
{{Pentose phosphate pathway enzymes}}
{{Glycosaminoglycan metabolism enzymes}}
{{Glycoprotein metabolism enzymes}}
{{Authority control}}

{{DEFAULTSORT:Carbohydrate Metabolism}}
[[Category:Carbohydrate metabolism]]

[[de:Glucose#Biochemie]]