View source for Fatty acid metabolism

{{split|discuss=Talk:Fatty acid metabolism#Split proposal|date=July 2025}}
{{short description|Set of biological processes}}
'''Fatty acid metabolism''' consists of various [[metabolism|metabolic]] processes involving or closely related to [[fatty acid]]s, a family of molecules classified within the [[lipid]] [[macronutrient]] category. These processes can mainly be divided into (1) [[catabolic]] processes that generate energy and (2) [[anabolic]] processes where they serve as building blocks for other compounds.<ref name=stryer1>{{cite book |last1=Stryer |first1= Lubert |title=In: Biochemistry. |chapter=Fatty acid metabolism. |edition=Fourth |location=New York |publisher=W.H. Freeman and Company |date=1995 |pages=603–628 |isbn=0-7167-2009-4 }}</ref>

In catabolism, fatty acids are metabolized to produce energy, mainly in the form of [[adenosine triphosphate]] (ATP). When compared to other macronutrient classes (carbohydrates and protein), fatty acids yield the most ATP on an energy per gram basis, when they are completely oxidized to CO<sub>2</sub> and water by [[beta oxidation]] and the [[citric acid cycle]].<ref name="oxidation_of_fats">[https://pharmaxchange.info/press/2013/10/oxidation-of-fatty-acids/ Oxidation of fatty acids]</ref> Fatty acids (mainly in the form of [[triglyceride]]s) are therefore the foremost storage form of fuel in most animals, and to a lesser extent in plants.

In anabolism, intact fatty acids are important precursors to triglycerides, phospholipids, second messengers, hormones and [[ketone bodies]]. For example, [[phospholipid]]s form the [[phospholipid bilayers]] out of which all the membranes of the cell are constructed from fatty acids. Phospholipids comprise the plasma membrane and other membranes that enclose all the [[organelle]]s within the cells, such as the [[Cell nucleus|nucleus]], the [[mitochondria]], [[endoplasmic reticulum]], and the [[Golgi apparatus]]. In another type of anabolism, fatty acids are modified to form other compounds such as [[second messenger]]s and [[Paracrine signaling|local hormone]]s. The [[prostaglandin]]s made from [[arachidonic acid]] stored in the cell membrane are probably the best-known of these local hormones.

== Fatty acid catabolism ==
[[File:Metabolism1.jpg|thumb|250px|A diagrammatic illustration of the process of lipolysis (in a fat cell) induced by high [[epinephrine]] and low [[insulin]] levels in the blood. Epinephrine binds to a [[Adrenergic receptor#β receptors|beta-adrenergic receptor]] in the cell membrane of the adipocyte, which causes [[Cyclic adenosine monophosphate|cAMP]] to be generated inside the cell. The cAMP activates a [[protein kinase]], which phosphorylates and thus, in turn, activates a [[hormone-sensitive lipase]] in the fat cell. This lipase cleaves free fatty acids from their attachment to glycerol in the fat stored in the fat droplet of the adipocyte. The free fatty acids and glycerol are then released into the blood. However more recent studies have shown that [[adipose triglyceride lipase]] has to first convert triacylglycerides to diacylglycerides, and that [[hormone-sensitive lipase]] converts the diacylglycerides to monoglycerides and free fatty acids. Monoglycerides are hydrolyzed by monoglyceride lipase.<ref name="pmid15891395">{{cite journal |vauthors = Zechner R, Strauss JG, Haemmerle G, Lass A, Zimmermann R |title=Lipolysis: pathway under construction |journal=Curr. Opin. Lipidol. |volume=16 |issue=3 |pages=333–40 |year=2005 |pmid=15891395|doi=10.1097/01.mol.0000169354.20395.1c |s2cid=35349649 }}</ref>  The activity of hormone sensitive lipase is regulated by the circulation hormones [[insulin]], [[glucagon]], [[norepinephrine]], and [[epinephrine]], as shown in the diagram.]]

[[File:Metabolism2.jpg|thumb|250px|A diagrammatic illustration of the transport of [[free fatty acids]] in the blood attached to [[Serum albumin|plasma albumin]], its diffusion across the cell membrane using a protein transporter, and its activation, using [[Adenosine triphosphate|ATP]], to form [[acyl-CoA]] in the [[cytosol]]. The illustration is, for diagrammatic purposes, of a 12 carbon fatty acid. Most fatty acids in human plasma are 16 or 18 carbon atoms long.]]

[[File:Metabolism3.jpg|thumb|250px|A diagrammatic illustration of the transfer of an acyl-CoA molecule across the [[inner membrane of the mitochondrion]] by [[Carnitine O-palmitoyltransferase|carnitine-acyl-CoA transferase]] (CAT). The illustrated acyl chain is, for diagrammatic purposes, only 12 carbon atoms long. Most fatty acids in human plasma are 16 or 18 carbon atoms long. CAT is inhibited by high concentrations of [[malonyl-CoA]] (the first committed step in [[fatty acid synthesis]]) in the cytoplasm. This means that fatty acid synthesis and fatty acid catabolism cannot occur simultaneously in any given cell.]]

[[File:Metabolism4.jpg|thumb|250px|A diagrammatic illustration of the process of the [[beta-oxidation]] of an acyl-CoA molecule in the mitochondrial matrix. During this process an acyl-CoA molecule which is 2 carbons shorter than it was at the beginning of the process is formed. Acetyl-CoA, water and 5 [[Adenosine triphosphate|ATP]] molecules are the other products of each beta-oxidative event, until the entire acyl-CoA molecule has been reduced to a set of [[acetyl-CoA]] molecules.]]

Fatty acids are stored as [[triglyceride]]s in the fat depots of [[adipose tissue]]. Between meals they are released as follows:
* [[Lipolysis]], the removal of the fatty acid chains from the glycerol to which they are bound in their storage form as triglycerides (or fats), is carried out by [[lipase]]s. These lipases are activated by high [[epinephrine]] and [[glucagon]] levels in the blood (or [[norepinephrine]] secreted by [[Sympathetic nervous system|sympathetic nerves]] in adipose tissue), caused by declining blood [[glucose]] levels after meals, which simultaneously lowers the [[insulin]] level in the blood.<ref name=stryer1 />
* Once freed from [[glycerol]], the free fatty acids enter the blood, which transports them, attached to plasma [[albumin]], throughout the body.<ref name="mobilization_of_fats">[https://pharmaxchange.info/press/2013/10/mobilization-and-cellular-uptake-of-stored-fats-triacylglycerols-with-animation/ Mobilization and cellular uptake of stored fats (triacylglycerols) (with animation)]</ref>
* Long-chain free fatty acids enter metabolizing cells (i.e. most living cells in the body except [[red blood cell]]s and [[neuron]]s in the [[central nervous system]]) through specific [[transport protein]]s, such as the [[Solute carrier family|SLC27]] family fatty acid transport protein.<ref>{{cite journal|last1=Stahl|first1=Andreas|title=A current review of fatty acid transport proteins (SLC27)|journal=Pflügers Archiv: European Journal of Physiology|date=1 February 2004|volume=447|issue=5|pages=722–727|doi=10.1007/s00424-003-1106-z|pmid=12856180|s2cid=2769738}}</ref><ref>{{cite journal|last1=Anderson|first1=Courtney M.|last2=Stahl|first2=Andreas|title=SLC27 fatty acid transport proteins|journal=Molecular Aspects of Medicine|date=April 2013|volume=34|issue=2–3|pages=516–528|doi=10.1016/j.mam.2012.07.010|pmid=23506886|pmc=3602789}}</ref> Red blood cells do not contain [[Mitochondrion|mitochondria]] and are therefore incapable of metabolizing fatty acids; the tissues of the central nervous system cannot use fatty acids, despite containing mitochondria, because long-chain fatty acids (as opposed to medium-chain fatty acids<ref name="Ebert 2003">{{Cite journal | last1=Ebert| first1=D.| last2=Haller| first2=RG.| last3=Walton| first3=ME.| title=Energy contribution of octanoate to intact rat brain metabolism measured by <sup>13</sup>C nuclear magnetic resonance spectroscopy| journal=J Neurosci| volume=23| issue=13| pages=5928–35|date=Jul 2003|  pmid=12843297 | doi=10.1523/JNEUROSCI.23-13-05928.2003| doi-access=free| pmc=6741266}}</ref><ref name="Marin Valencia 2013">{{Cite journal| last1=Marin-Valencia| first1=I. | last2=Good| first2=LB.| last3=Ma| first3=Q.| last4=Malloy| first4=CR.| last5=Pascual| first5=JM.| title=Heptanoate as a neural fuel: energetic and neurotransmitter precursors in normal and glucose transporter I-deficient (G1D) brain| journal=J Cereb Blood Flow Metab| volume=33| issue=2| pages=175–82|date=Feb 2013 | doi=10.1038/jcbfm.2012.151| pmid=23072752| pmc=3564188 }}</ref>) cannot cross the [[Blood–brain barrier|blood-brain barrier]]<ref name=stryer10>{{cite book |last1= Stryer |first1= Lubert | title=In: Biochemistry. |chapter= Fatty acid metabolism. |edition= Fourth |location= New York |publisher= W.H. Freeman and Company|date= 1995 |pages= 770–771 |isbn= 0-7167-2009-4 }}</ref> into the [[interstitial fluid]]s that bathe these cells.
* Once inside the cell, [[long-chain-fatty-acid—CoA ligase]] catalyzes the reaction between a fatty acid molecule with [[Adenosine triphosphate|ATP]] (which is broken down to [[Adenosine monophosphate|AMP]] and inorganic pyrophosphate) to give a fatty acyl-adenylate, which then reacts with free [[coenzyme A]] to give a fatty [[acyl-CoA]] molecule.
* In order for the acyl-CoA to enter the mitochondrion the carnitine shuttle is used:<ref name=stryer2>{{cite book |last1= Stryer |first1= Lubert | title=Biochemistry. | edition= Fourth |location= New York |publisher= W.H. Freeman and Company|date= 1995 |pages= 510–515, 581–613, 775–778 |isbn= 0-7167-2009-4 }}</ref><ref>[https://pharmaxchange.info/press/2013/10/activation-and-transportation-of-fatty-acids-to-the-mitochondria-via-the-carnitine-shuttle-with-animation/ Activation and transportation of fatty acids to the mitochondria via the carnitine shuttle (with animation)]</ref><ref name="VivoBohan1998">{{cite journal|last1=Vivo|first1=Darryl C.|last2=Bohan|first2=Timothy P.|last3=Coulter|first3=David L.|last4=Dreifuss|first4=Fritz E.|last5=Greenwood|first5=Robert S.|last6=Nordli|first6=Douglas R.|last7=Shields|first7=W. Donald|last8=Stafstrom|first8=Carl E.|last9=Tein|first9=Ingrid|title=l-Carnitine Supplementation in Childhood Epilepsy: Current Perspectives|journal=Epilepsia|volume=39|issue=11|year=1998|pages=1216–1225|issn=0013-9580|doi=10.1111/j.1528-1157.1998.tb01315.x|pmid=9821988|s2cid=28692799|doi-access=free}}</ref>

# Acyl-CoA is transferred to the hydroxyl group of carnitine by [[carnitine palmitoyltransferase I]], located on the cytosolic faces of the [[outer mitochondrial membrane|outer]] and [[inner mitochondrial membrane]]s.
# Acyl-carnitine is shuttled inside by a [[carnitine-acylcarnitine translocase]], as a carnitine is shuttled outside.
# Acyl-carnitine is converted back to acyl-CoA by [[carnitine palmitoyltransferase II]], located on the interior face of the [[inner mitochondrial membrane]]. The liberated carnitine is shuttled back to the cytosol, as an acyl-CoA is shuttled into the mitochondrial matrix.
* [[Beta oxidation]], in the mitochondrial matrix, then cuts the long carbon chains of the fatty acids (in the form of acyl-CoA molecules) into a series of two-carbon ([[Acetic acid|acetate]]) units, which, combined with [[Coenzyme A|co-enzyme A]], form molecules of [[acetyl CoA]], which condense with [[Oxaloacetic acid|oxaloacetate]] to form [[Citric acid|citrate]] at the "beginning" of the [[citric acid cycle]].<ref name="oxidation_of_fats">[https://pharmaxchange.info/press/2013/10/oxidation-of-fatty-acids/ Oxidation of fatty acids]</ref> It is convenient to think of this reaction as marking the "starting point" of the cycle, as this is when fuel - acetyl-CoA - is added to the cycle, which will be dissipated as CO{{sub|2}} and H{{sub|2}}O with the release of a substantial quantity of energy captured in the form of [[Adenosine triphosphate|ATP]], during the course of each turn of the cycle and subsequent [[oxidative phosphorylation]].

: Briefly, the steps in beta oxidation are as follows:<ref name="oxidation_of_fats"/>

# Dehydrogenation by [[acyl-CoA dehydrogenase]], yielding 1 [[flavin adenine dinucleotide|FADH{{sub|2}}]]
# Hydration by [[enoyl-CoA hydratase]]
# Dehydrogenation by [[3-hydroxyacyl-CoA dehydrogenase]], yielding 1 [[Nicotinamide adenine dinucleotide|NADH + H<sup>+</sup>]]
# Cleavage by [[thiolase]], yielding 1 [[acetyl-CoA]] and a fatty acid that has now been shortened by 2 carbons (forming a new, shortened [[acyl-CoA]])

:This beta oxidation reaction is repeated until the fatty acid has been completely reduced to [[acetyl-CoA]] or, in the case of fatty acids with odd numbers of carbon atoms, [[acetyl-CoA]] and 1&nbsp;molecule of [[propionyl-CoA]] per molecule of fatty acid. Each beta oxidative cut of the acyl-CoA molecule eventually yields 5 [[Adenosine triphosphate|ATP]] molecules in oxidative phosphorylation.<ref>[https://pharmaxchange.info/press/2013/10/oxidation-of-odd-carbon-chain-length-fatty-acids/ Oxidation of odd carbon chain length fatty acids]</ref><ref>[https://pharmaxchange.info/press/2013/10/oxidation-of-unsaturated-fatty-acids/ Oxidation of unsaturated fatty acids]</ref>
* The acetyl-CoA produced by beta oxidation enters the [[citric acid cycle]] in the mitochondrion by combining with [[Oxaloacetic acid|oxaloacetate]] to form [[citric acid|citrate]]. Coupled to oxidative phosphorylation this results in the complete combustion of the acetyl-CoA to CO{{sub|2}} and water. The energy released in this process is captured in the form of 1 [[Guanosine triphosphate|GTP]] and 11 [[Adenosine triphosphate|ATP]] molecules per acetyl-CoA molecule oxidized.<ref name="oxidation_of_fats"/><ref name=stryer2 /> This is the fate of acetyl-CoA wherever beta oxidation of fatty acids occurs, except under certain circumstances in the [[liver]].

: The propionyl-CoA is later converted into [[succinyl-CoA]] through [[biotin]]-dependant [[propionyl-CoA carboxylase]] (PCC) and [[vitamin B12|Vitamin B<sub>12</sub>]]-dependant [[methylmalonyl-CoA mutase]] (MCM), sequentially.<ref>{{cite journal | vauthors = Wongkittichote P, Ah Mew N, Chapman KA | title = Propionyl-CoA carboxylase - A review | journal = Molecular Genetics and Metabolism | volume = 122 | issue = 4 | pages = 145–152 | date = December 2017 | pmid = 29033250 | pmc = 5725275 | doi = 10.1016/j.ymgme.2017.10.002 }}</ref><ref>{{cite journal |vauthors=Halarnkar PP, Blomquist GJ |title=Comparative aspects of propionate metabolism |journal=Comp. Biochem. Physiol. B |volume=92 |issue=2 |pages=227–31 |year=1989 |pmid=2647392 |doi=10.1016/0305-0491(89)90270-8}}</ref> Succinyl-CoA is first converted to malate, and then to pyruvate where it is then transported to the matrix to enter the citric acid cycle.

In the liver oxaloacetate can be wholly or partially diverted into the [[gluconeogenesis|gluconeogenic pathway]] during fasting, starvation, a low carbohydrate diet, prolonged strenuous exercise, and in uncontrolled [[Diabetes mellitus#Type 1|type 1 diabetes mellitus]]. Under these circumstances, oxaloacetate is hydrogenated to [[Malic acid|malate]], which is then removed from the mitochondria of the liver cells to be converted into [[glucose]] in the cytoplasm of the liver cells, from where it is released into the blood.<ref name=stryer2 /> In the liver, therefore, oxaloacetate is unavailable for condensation with acetyl-CoA when significant gluconeogenesis has been stimulated by low (or absent) [[insulin]] and high [[glucagon]] concentrations in the blood. Under these conditions, acetyl-CoA is diverted to the formation of [[Acetoacetic acid|acetoacetate]] and [[beta-Hydroxybutyric acid|beta-hydroxybutyrate]].<ref name=stryer2 /> Acetoacetate, beta-hydroxybutyrate, and their spontaneous breakdown product, [[acetone]], are frequently, but confusingly, known as [[ketone bodies]] (as they are not "bodies" at all, but water-soluble chemical substances). The ketones are released by the liver into the blood. All cells with mitochondria can take up ketones from the blood and reconvert them into acetyl-CoA, which can then be used as fuel in their citric acid cycles, as no other tissue can divert its oxaloacetate into the gluconeogenic pathway in the way that this can occur in the liver. Unlike free fatty acids, ketones can cross the [[blood–brain barrier]] and are therefore available as fuel for the cells of the [[central nervous system]], acting as a substitute for glucose, on which these cells normally survive.<ref name=stryer2 /> The occurrence of high levels of ketones in the blood during starvation, a low carbohydrate diet, prolonged heavy exercise, or uncontrolled type 1 diabetes mellitus is known as [[ketosis]], and, in its extreme form, in out-of-control type 1 diabetes mellitus, as [[ketoacidosis]].
:The glycerol released by lipase action is [[phosphorylate]]d by [[glycerol kinase]] in the liver (the only tissue in which this reaction can occur), and the resulting [[glycerol 3-phosphate]] is oxidized to [[dihydroxyacetone phosphate]]. The glycolytic enzyme [[triose phosphate isomerase]] converts this compound to [[glyceraldehyde 3-phosphate]], which is oxidized via [[glycolysis]], or converted to glucose via [[gluconeogenesis]].

===Carbohydrate synthesis from glycerol and fatty acids===
Fatty acids are broken down to acetyl-CoA by means of beta oxidation inside the mitochondria, whereas [[Fatty acid synthesis|fatty acids are synthesized]] from acetyl-CoA outside the mitochondria, in the cytosol. The two pathways are distinct, not only in where they occur, but also in the reactions that occur, and the substrates that are used. The two pathways are mutually inhibitory, preventing the acetyl-CoA produced by beta-oxidation from entering the synthetic pathway via the [[acetyl-CoA carboxylase]] reaction.<ref name=stryer1 /> It can also not be converted to [[pyruvic acid|pyruvate]] as the [[pyruvate dehydrogenase complex]] reaction is irreversible.<ref name=stryer2 /> Instead the acetyl-CoA produced by the beta-oxidation of fatty acids condenses with [[oxaloacetic acid|oxaloacetate]], to enter the [[citric acid cycle]]. During each turn of the cycle, two carbon atoms leave the cycle as CO{{sub|2}} in the decarboxylation reactions catalyzed by [[isocitrate dehydrogenase]] and [[alpha-ketoglutarate dehydrogenase]]. Thus each turn of the citric acid cycle oxidizes an acetyl-CoA unit while regenerating the oxaloacetate molecule with which the acetyl-CoA had originally combined to form citric acid. The decarboxylation reactions occur before [[malic acid|malate]] is formed in the cycle.<ref name=stryer1 /> Only plants possess the enzymes to convert acetyl-CoA into oxaloacetate from which malate can be formed to ultimately be converted to glucose.<ref name=stryer1 />

However, acetyl-CoA can be converted to acetoacetate, which can decarboxylate to [[acetone]] (either spontaneously, or catalyzed by [[acetoacetate decarboxylase]]). It can then be further metabolized to isopropanol which is excreted in breath/urine, or by [[CYP2E1]] into [[hydroxyacetone]] (acetol). Acetol can be converted to [[propylene glycol]]. This converts to [[pyruvate]] (by two alternative enzymes), or [[propionaldehyde]], or to [[lactaldehyde|<small>L</small>-lactaldehyde]] then [[lactic acid|<small>L</small>-lactate]] (the common lactate isomer).<ref>{{cite journal | author = Ruddick JA | year = 1972 | title = Toxicology, metabolism, and biochemistry of 1,2-propanediol | journal = Toxicol Appl Pharmacol | volume = 21 | issue = 1 | pages = 102–111 | doi = 10.1016/0041-008X(72)90032-4 | pmid = 4553872| bibcode = 1972ToxAP..21..102R }}</ref><ref name=Glew2010>{{cite journal|url=https://www.ajol.info/index.php/njps/issue/view/9725 |last1=Glew |first1=Robert H|title=You Can Get There From Here: Acetone, Anionic Ketones and Even-Carbon Fatty Acids can Provide Substrates for Gluconeogenesis|journal=Nigerian Journal of Physiological Science|volume=25 |issue=1 |access-date=7 August 2016|archive-url=https://web.archive.org/web/20130926031021/http://www.bioline.org.br/request?np10002|pages=2–4|others=Invited review|archive-date=26 September 2013}}</ref><ref name="ParkKlapa1999">{{cite journal|last1=Park|first1=Sung M.|last2=Klapa|first2=Maria I.|last3=Sinskey|first3=Anthony J.|last4=Stephanopoulos|first4=Gregory|title=Metabolite and isotopomer balancing in the analysis of metabolic cycles: II. Applications|journal=Biotechnology and Bioengineering|page=398|volume=62|issue=4|year=1999|issn=0006-3592|doi=10.1002/(sici)1097-0290(19990220)62:4<392::aid-bit2>3.0.co;2-s|pmid=9921151|url=https://web.mit.edu/biology/sinskey/www/SMPark99.pdf}}</ref> Another pathway turns acetol to [[methylglyoxal]], then to [[pyruvate]], or to [[lactaldehyde|<small>D</small>-lactaldehyde]] (via <small>S-D</small>-lactoyl-glutathione or otherwise) then [[lactic acid|<small>D</small>-lactate]].<ref name="Glew2010"/><ref>{{cite journal | author = Miller DN, Bazzano G | year = 1965 | title = Propanediol metabolism and its relation to lactic acid metabolism | journal = Ann NY Acad Sci | volume = 119 | pages = 957–973 | bibcode = 1965NYASA.119..957M | last2 = Bazzano | doi = 10.1111/j.1749-6632.1965.tb47455.x | pmid = 4285478 | issue = 3| s2cid = 37769342 }}</ref><ref>{{Cite journal |author1=D. L. Vander Jagt |author2=B. Robinson |author3=K. K. Taylor |author4=L. A. Hunsaker | title = Reduction of trioses by NADPH-dependent aldo-keto reductases. Aldose reductase, methylglyoxal, and diabetic complications | journal = [[The Journal of Biological Chemistry]] | volume = 267 | issue = 7 | pages = 4364–4369 | year = 1992 |doi=10.1016/S0021-9258(18)42844-X | pmid = 1537826|doi-access=free }}</ref> D-lactate metabolism (to glucose) is slow or impaired in humans, so most of the D-lactate is excreted in the urine; thus <small>D</small>-lactate derived from acetone can contribute significantly to the metabolic acidosis associated with ketosis or isopropanol intoxication.<ref name="Glew2010"/> <small>L</small>-Lactate can complete the net conversion of fatty acids into glucose. The first experiment to show conversion of acetone to glucose was carried out in 1951. This, and further experiments used carbon [[isotopic labelling]].<ref name="ParkKlapa1999" /> Up to 11% of the glucose can be derived from acetone during starvation in humans.<ref name="ParkKlapa1999" />

The glycerol released into the blood during the [[lipolysis]] of triglycerides in adipose tissue can only be taken up by the liver. Here it is converted into [[glycerol 3-phosphate]] by the action of [[glycerol kinase]] which hydrolyzes one molecule of [[Adenosine triphosphate|ATP]] per glycerol molecule which is phosphorylated. Glycerol 3-phosphate is then oxidized to [[dihydroxyacetone phosphate]], which is, in turn, converted into [[glyceraldehyde 3-phosphate]] by the enzyme [[triose phosphate isomerase]]. From here the three carbon atoms of the original glycerol can be oxidized via [[glycolysis]], or converted to glucose via [[gluconeogenesis]].<ref name=stryer2 />

==Other functions and uses of fatty acids==

===Intracellular signaling===
[[File:1-palmitoyl-2-oleoyl-glycerol.svg|class=skin-invert-image|Chemical structure of the diglyceride 1-palmitoyl-2-oleoyl-glycerol|thumb|upright=2.0|right]]
Fatty acids are an integral part of the phospholipids that make up the bulk of the [[plasma membrane]]s, or cell membranes, of cells. These phospholipids can be cleaved into [[diacylglycerol]] (DAG) and [[inositol trisphosphate]] (IP{{sub|3}}) through [[hydrolysis]] of the phospholipid, [[phosphatidylinositol 4,5-bisphosphate]] (PIP{{sub|2}}), by the cell membrane bound enzyme [[phospholipase C]] (PLC).<ref name=stryer4>{{cite book |last1= Stryer |first1= Lubert | title=In: Biochemistry. |chapter= Signal transduction cascades. |edition= Fourth |location= New York |publisher= W.H. Freeman and Company|date= 1995 |pages= 343–350 |isbn= 0-7167-2009-4 }}</ref>

===Eicosanoid paracrine hormones===
[[File:Arachidonic_acid_structure.svg|class=skin-invert-image|thumb|right|[[Arachidonic acid]]]]
[[File:Prostaglandin E1.svg|class=skin-invert-image|thumb|right|[[Alprostadil|Prostaglandin E<sub>1</sub> - Alprostadil]]]]

One product of fatty acid metabolism are the [[prostaglandin]]s, compounds having diverse [[hormone]]-like effects in animals. Prostaglandins have been found in almost every [[tissue (biology)|tissue]] in humans and other animals. They are [[enzymatically]] derived from arachidonic acid, a 20-carbon polyunsaturated fatty acid. Every prostaglandin therefore contains 20 [[carbon]] atoms, including a [[carbon ring|5-carbon ring]]. They are a subclass of [[eicosanoid]]s and form the [[prostanoid]] class of fatty acid derivatives.<ref name=stryer3>{{cite book |last1= Stryer |first1= Lubert | title=In: Biochemistry. |chapter= Eicosanoid hormones are derived from fatty acids.|edition= Fourth |location= New York |publisher= W.H. Freeman and Company|date= 1995 |pages= 624–627 |isbn= 0-7167-2009-4 }}</ref>

The prostaglandins are synthesized in the cell membrane by the cleavage of arachidonate from the phospholipids that make up the membrane. This is catalyzed either by [[Phospholipase A2|phospholipase A{{sub|2}}]] acting directly on a membrane phospholipid, or by a lipase acting on DAG (diacyl-glycerol). The arachidonate is then acted upon by the [[cyclooxygenase]] component of [[prostaglandin synthase]]. This forms a [[cyclopentane]] ring roughly in the middle of the fatty acid chain. The reaction also adds 4 oxygen atoms derived from two molecules of O{{sub|2}}. The resulting molecule is prostaglandin G{{sub|2}}, which is converted by the hydroperoxidase component of the enzyme complex into prostaglandin H{{sub|2}}. This highly unstable compound is rapidly transformed into other prostaglandins, prostacyclin and thromboxanes.<ref name=stryer3 /> These are then released into the interstitial fluids surrounding the cells that have manufactured the eicosanoid hormone.

If arachidonate is acted upon by a [[lipoxygenase]] instead of cyclooxygenase, [[hydroxyeicosatetraenoic acid]]s and [[leukotriene]]s are formed. They also act as local hormones.

Prostaglandins have two derivatives: [[prostacyclin]]s and [[thromboxane]]s. Prostacyclins are powerful locally acting [[vasodilator]]s and inhibit the aggregation of blood [[platelet]]s. Through their role in vasodilation, prostacyclins are also involved in [[inflammation]]. They are synthesized in the walls of blood vessels and serve the physiological function of preventing needless clot formation, as well as regulating the contraction of [[smooth muscle]] tissue.<ref name="isbn0-87893-617-3">{{cite book |author=Nelson, Randy F. |title=An introduction to behavioral endocrinology |edition=3rd |publisher=Sinauer Associates |location=Sunderland, Mass |year=2005 |pages=100 |isbn=978-0-87893-617-5 }}</ref> Conversely, thromboxanes (produced by platelet cells) are [[vasoconstrictor]]s and facilitate platelet aggregation. Their name comes from their role in clot formation ([[thrombosis]]).

==Dietary sources of fatty acids, their digestion, absorption, transport in the blood and storage<!--Linked from 'Monoglyceride'-->==
[[File:Emulsion formation.jpg|thumb|300 px|right|Dietary fats are emulsified in the duodenum by soaps in the form of bile salts and phospholipids, such as [[phosphatidylcholine]]. The fat droplets thus formed can be attacked by pancreatic lipase.]]
[[File:Cholic acid.jpg|thumb|right|300 px|Structure of a bile acid (cholic acid), represented in the standard form, a semi-realistic 3D form, and a diagrammatic 3D form]]
[[File:Cholic acid micelles.jpg|thumb|right|300 px|Diagrammatic illustration of mixed micelles formed in the duodenum in the presence of bile acids (e.g. cholic acid) and the digestion products of fats, the fat soluble vitamins and cholesterol.]]

A significant proportion of the fatty acids in the body are obtained from the diet, in the form of triglycerides of either animal or plant origin. The fatty acids in the fats obtained from land animals tend to be saturated, whereas the fatty acids in the triglycerides of fish and plants are often polyunsaturated and therefore present as oils.

These [[triglyceride]]s cannot be absorbed by the [[intestine]].<ref name="mehta_digestion">[https://pharmaxchange.info/press/2013/10/digestion-of-fats-triacylglycerols/ Digestion of fats (triacylglycerols)]</ref> They are broken down into [[Monoglyceride|mono-]] and [[Diglyceride|di-glycerides]] plus free fatty acids (but no free glycerol) by [[pancreatic lipase]], which forms a 1:1 complex with a protein called [[colipase]] (also a constituent of pancreatic juice), which is necessary for its activity. The [[activated complex]] can work only at a water-fat interface. Therefore, it is essential that fats are first [[Emulsion|emulsified]] by [[bile salt]]s for optimal activity of these enzymes.<ref name="pmid14097367">{{cite journal |author=Hofmann AF |title=The function of bile salts in fat absorption. The solvent properties of dilute micellar solutions of conjugated bile salts|journal=Biochem. J. |volume=89 |pages=57–68 |date= 1963  |issue=1 |pmid=14097367 |pmc=1202272 |doi=10.1042/bj0890057}}</ref> The digestion products consisting of a mixture of tri-, di- and monoglycerides and free fatty acids, which, together with the other fat soluble contents of the diet (e.g. the fat soluble vitamins and cholesterol) and bile salts form mixed [[micelle]]s, in the watery duodenal contents (see diagrams on the right).<ref name="mehta_digestion"/><ref name=stryer5>{{cite book |last1= Stryer |first1= Lubert | title=In: Biochemistry. |chapter= Membrane structures and dynamics. |edition= Fourth |location= New York |publisher= W.H. Freeman and Company|date= 1995 |pages= 268–270 |isbn= 0-7167-2009-4 }}</ref>

The contents of these micelles (but not the bile salts) enter the [[enterocyte]]s (epithelial cells lining the small intestine) where they are resynthesized into triglycerides, and packaged into [[chylomicron]]s which are released into the [[lacteal]]s (the capillaries of the [[lymph system]] of the intestines).<ref>{{cite book|first1=Sareen S.|last1=Gropper|first2=Jack L.|last2=Smith|title=Advanced nutrition and human metabolism|date=2013|publisher=Wadsworth/Cengage Learning|location=Belmont, CA|isbn=978-1133104056|edition=6th}}</ref> These lacteals drain into the [[thoracic duct]] which empties into the venous blood at the junction of the left jugular and left subclavian veins on the lower left hand side of the neck. This means that the fat-soluble products of digestion are discharged directly into the general circulation, without first passing through the liver, unlike all other digestion products. The reason for this peculiarity is unknown.<ref name=Graysanatomy>{{cite book |last1=Williams |first1= Peter L.|last2=Warwick |first2= Roger|last3=Dyson |first3= Mary|last4=Bannister |first4= Lawrence H. |title=In: Gray's Anatomy |chapter= Angiology. |edition= Thirty-seventh |location= Edinburgh |publisher= Churchill Livingstone|date= 1989 |pages= 841–843 |isbn= 0443-041776 }}</ref>

[[File:2512 Chylomicrons Contain Triglycerides Cholesterol Molecules and Other Lipids.jpg|thumb|right| 200 px| A schematic diagram of a chylomicron]]

The chylomicrons circulate throughout the body, giving the [[blood plasma]] a milky or creamy appearance after a fatty meal.{{Citation needed|date=September 2017}} [[Lipoprotein lipase]] on the [[Endothelium|endothelial surfaces]] of the capillaries, especially in [[adipose tissue]], but to a lesser extent also in other tissues, partially digests the chylomicrons into free fatty acids, glycerol and chylomicron remnants. The fatty acids are absorbed by the adipocytes{{Citation needed|date=September 2017}}, but the glycerol and [[Chylomicron#Chylomicron remnants|chylomicron remnants]] remain in the blood plasma, ultimately to be removed from the circulation by the liver. The free fatty acids released by the digestion of the chylomicrons are absorbed by the adipocytes{{Citation needed|date=September 2017}}, where they are resynthesized into triglycerides using glycerol derived from glucose in the [[Glycolysis|glycolytic pathway]]{{Citation needed|date=September 2017}}. These triglycerides are stored, until needed for the fuel requirements of other tissues, in the fat droplet of the [[adipocyte]].

The [[liver]] absorbs a proportion of the glucose from the blood in the [[portal vein]] coming from the intestines. After the liver has replenished its [[glycogen]] stores (which amount to only about 100 g of glycogen when full) much of the rest of the glucose is converted into fatty acids as described below. These fatty acids are combined with glycerol to form triglycerides which are packaged into droplets very similar to chylomicrons, but known as [[very low-density lipoprotein]]s (VLDL). These VLDL droplets are processed in exactly the same manner as chylomicrons, except that the VLDL remnant is known as an [[intermediate-density lipoprotein]] (IDL), which is capable of scavenging cholesterol from the blood. This converts IDL into [[low-density lipoprotein]] (LDL), which is taken up by cells that require cholesterol for incorporation into their cell membranes or for synthetic purposes (e.g. the formation of the [[steroid hormone]]s). The remainder of the LDLs is removed by the liver.<ref name=stryer6>{{cite book |last1= Stryer |first1= Lubert | title=In: Biochemistry. |chapter=Biosynthesis of membrane lipids and steroids. |edition= Fourth |location= New York |publisher= W.H. Freeman and Company|date= 1995 |pages= 697–700 |isbn= 0-7167-2009-4 }}</ref>

[[Adipose tissue]] and lactating [[mammary gland]]s also take up glucose from the blood for conversion into triglycerides. This occurs in the same way as in the liver, except that these tissues do not release the triglycerides thus produced as VLDL into the blood. Adipose tissue cells store the triglycerides in their fat droplets, ultimately to release them again as free fatty acids and glycerol into the blood (as described [[Fatty acid metabolism#Fatty acid catabolism|above]]), when the plasma concentration of insulin is low, and that of glucagon and/or epinephrine is high.<ref>{{cite journal|last1=Stralfors|first1=Peter|last2=Honnor|first2=Rupert C.|title=Insulin-induced dephosphorylation of hormone-sensitive lipase|journal=European Journal of Biochemistry|year=1989|volume=182|issue=2|pages=379–385|doi=10.1111/j.1432-1033.1989.tb14842.x|pmid=2661229|doi-access=free}}</ref> Mammary glands discharge the fat (as cream fat droplets) into the milk that they produce under the influence of the [[anterior pituitary]] hormone [[prolactin]].

All cells in the body need to manufacture and maintain their membranes and the membranes of their organelles. Whether they rely entirely on free fatty acids absorbed from the blood, or are able to synthesize their own fatty acids from blood glucose, is not known. The cells of the [[central nervous system]] will almost certainly have the capability of manufacturing their own fatty acids, as these molecules cannot reach them through the [[blood–brain barrier]].<ref name="stryer" /> However, it is unknown how they are reached by the [[essential fatty acid]]s, which mammals cannot synthesize themselves but are nevertheless important components of cell membranes (and [[Fatty acid metabolism#Eicosanoid paracrine hormones|other functions]] described above).

==Fatty acid synthesis==
{{Main|Fatty acid synthesis}}

[[File:Saturated Fatty Acid Synthesis.svg|class=skin-invert-image|thumb|left|400px| Synthesis of saturated fatty acids via Fatty Acid Synthase II in ''Escherichia coli'']]
Much like [[beta-oxidation]], straight-chain fatty acid synthesis occurs via the six recurring reactions shown below, until the 16-carbon [[palmitic acid]] is produced.<ref name=transFA>Dijkstra, Albert J., R. J. Hamilton, and Wolf Hamm. "Fatty Acid Biosynthesis." Trans Fatty Acids. Oxford: Blackwell Pub., 2008. 12. Print.</ref><ref>{{cite web|title=MetaCyc pathway: superpathway of fatty acids biosynthesis |publisher=BioCyc|website=MetaCyc Metabolic Pathway Database|url=http://www.biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-6285&detail-level=3|id=(''E. coli'') }}</ref>

The diagrams presented show how fatty acids are synthesized in microorganisms and list the enzymes found in ''[[Escherichia coli]]''.<ref name=transFA /> These reactions are performed by [[fatty acid synthase]] II (FASII), which in general contains multiple enzymes that act as one complex. FASII is present in [[prokaryote]]s, plants, fungi, and parasites, as well as in [[mitochondria]].<ref name=lipidlib>{{cite book|url=https://lipidlibrary.aocs.org/ |last1=Christie|first1=William W. |editor1=((American Oil Chemists' Society))|editor1-link=American Oil Chemists' Society |title=AOCS Lipid Library|chapter=Fatty Acids: Straight-chain Saturated, Structure, Occurrence and Biosynthesis |access-date=2011-05-02 |archive-url=https://web.archive.org/web/20110721024641/http://lipidlibrary.aocs.org/lipids/fa_sat/index.htm |archive-date=2011-07-21|date=20 April 2011}}</ref>

In animals as well as some fungi such as yeast, these same reactions occur on fatty acid synthase I (FASI), a large dimeric protein that has all of the enzymatic activities required to create a fatty acid. FASI is less efficient than FASII; however, it allows for the formation of more molecules, including "medium-chain" fatty acids via early chain termination.<ref name=lipidlib /> Enzymes, acyltransferases and transacylases, incorporate fatty acids in phospholipids, triacylglycerols, etc. by transferring fatty acids between an acyl acceptor and donor. They also have the task of synthesizing bioactive lipids as well as their precursor molecules.<ref>{{Cite journal|date=2014-01-01|title=Acyltransferases and transacylases that determine the fatty acid composition of glycerolipids and the metabolism of bioactive lipid mediators in mammalian cells and model organisms|journal=Progress in Lipid Research|language=en|volume=53|pages=18–81|doi=10.1016/j.plipres.2013.10.001|pmid=24125941|issn=0163-7827|last1=Yamashita|first1=Atsushi|last2=Hayashi|first2=Yasuhiro|last3=Nemoto-Sasaki|first3=Yoko|last4=Ito|first4=Makoto|last5=Oka|first5=Saori|last6=Tanikawa|first6=Takashi|last7=Waku|first7=Keizo|last8=Sugiura|first8=Takayuki}}</ref>

Once a 16:0 carbon fatty acid has been formed, it can undergo a number of modifications, resulting in desaturation and/or elongation. Elongation, starting with stearate (18:0), is performed mainly in the [[endoplasmic reticulum]] by several membrane-bound enzymes. The enzymatic steps involved in the elongation process are principally the same as those carried out by [[fatty acid synthesis]], but the four principal successive steps of the elongation are performed by individual proteins, which may be physically associated.<ref>{{cite web|title=MetaCyc pathway: stearate biosynthesis I (animals)|website=MetaCyc Metabolic Pathway Database|publisher=BioCyc|url=http://www.biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-5972&detail-level=3}}</ref><ref>{{cite web|title=MetaCyc pathway: very long chain fatty acid biosynthesis II|website=MetaCyc Metabolic Pathway Database|publisher=BioCyc|url=http://www.biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-7036&detail-level=3}}</ref>

{| class="wikitable" |-
! Step
! Enzyme
! Reaction
! Description
|-
| (a)
| [[(acyl-carrier-protein) S-acetyltransferase|Acetyl-CoA:ACP transacylase]]
| [[File:Acety-CoA ACP transacylase reaction.svg|class=skin-invert-image|center|180px]]
| Activates acetyl-CoA for reaction with malonyl-ACP
|-
| (b)
| [[(acyl-carrier-protein) S-malonyltransferase|Malonyl-CoA:ACP transacylase]]
| [[File:Malonyl-CoA ACP transacylase reaction.svg|class=skin-invert-image|Center|180px]]
| Activates malonyl-CoA for reaction with acetyl-ACP
|-
| (c)
| [[Beta-ketoacyl-ACP synthase I|3-ketoacyl-ACP synthase]]
| [[File:3-ketoacyl-ACP synthetase reaction.svg|class=skin-invert-image|center|180px]]
| Reacts ACP-bound acyl chain with chain-extending malonyl-ACP
|-
| (d)
| [[3-oxoacyl-(acyl-carrier-protein) reductase|3-ketoacyl-ACP reductase]]
| [[File:3-ketoacyl-ACP reductase reaction.svg|class=skin-invert-image|center|180px]]
| Reduces the carbon 3 ketone to a hydroxyl group
|-
| (e)
| [[3-Hydroxyacyl ACP dehydrase]]
| [[File:3-hydroxyacyl-ACP dehydrase reaction.svg|class=skin-invert-image|center|180px]]
| Eliminates water
|-
| (f)
| [[Enoyl-acyl carrier protein reductase|Enoyl-ACP reductase]]
| [[File:Enoyl-ACP reductase reaction.svg|class=skin-invert-image|center|180px]]
| Reduces the C2-C3 double bond.
|}

Abbreviations: ACP – [[Acyl carrier protein]], CoA – [[Coenzyme A]], NADP – [[Nicotinamide adenine dinucleotide phosphate]].

Note that during fatty synthesis the reducing agent is [[Nicotinamide adenine dinucleotide phosphate|NADPH]], whereas [[Nicotinamide adenine dinucleotide|NAD]] is the oxidizing agent in [[beta-oxidation]] (the breakdown of fatty acids to acetyl-CoA). This difference exemplifies a general principle that NADPH is consumed during biosynthetic reactions, whereas NADH is generated in energy-yielding reactions.<ref name=stryer>{{cite book |last1= Stryer |first1= Lubert | title=Biochemistry. |edition= Fourth |location= New York |publisher= W.H. Freeman and Company|date= 1995 |pages= 559–565, 614–623|isbn= 0-7167-2009-4 }}</ref> (Thus NADPH is also required for the synthesis of [[cholesterol]] from acetyl-CoA; while NADH is generated during [[glycolysis]].) The source of the NADPH is two-fold. When [[Malic acid|malate]] is oxidatively decarboxylated by “NADP<sup>+</sup>-linked malic enzyme" [[Pyruvic acid|pyruvate]], CO{{sub|2}} and NADPH are formed. NADPH is also formed by the [[pentose phosphate pathway]] which converts glucose into ribose, which can be used in synthesis of [[nucleotide]]s and [[nucleic acid]]s, or it can be catabolized to pyruvate.<ref name=stryer />

===Glycolytic end products are used in the conversion of carbohydrates into fatty acids===
{{See also|Citric acid cycle#Citric acid cycle intermediates serve as substrates for biosynthetic processes}}

In humans, fatty acids are formed from carbohydrates predominantly in the liver and [[adipose tissue]], as well as in the [[mammary gland]]s during lactation. The [[Pyruvic acid|pyruvate]] produced by [[glycolysis]] is an important intermediary in the conversion of carbohydrates into fatty acids and cholesterol.<ref name="stryer" /> This occurs via the conversion of pyruvate into acetyl-CoA in the mitochondrion. However, this acetyl-CoA needs to be transported into cytosol where the synthesis of fatty acids and cholesterol occurs. This cannot occur directly. To obtain cytosolic acetyl-CoA, [[Citric acid|citrate]] (produced by the condensation of acetyl-CoA with oxaloacetate) is removed from the [[citric acid cycle]] and carried across the inner mitochondrial membrane into the cytosol.<ref name="stryer" /> There it is cleaved by [[ATP citrate lyase]] into acetyl-CoA and oxaloacetate. The oxaloacetate is returned to mitochondrion as malate (and then converted back into oxaloacetate to transfer more acetyl-CoA out of the mitochondrion).<ref name="ferre">{{cite journal | doi = 10.1159/000100426 | title = SREBP-1c Transcription Factor and Lipid Homeostasis: Clinical Perspective | journal = Hormone Research | year = 2007 | first = P. | last = Ferre |author2=F. Foufelle | volume = 68 | issue = 2 | pages = 72–82| pmid = 17344645 | url = http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowFulltext&ArtikelNr=100426&Ausgabe=232805&ProduktNr=224036 | access-date = 2010-08-30 | quote = this process is outlined graphically in page 73| doi-access = free }}</ref> The cytosolic acetyl-CoA is carboxylated by [[acetyl-CoA carboxylase]] into [[malonyl-CoA]], the first committed step  in the  synthesis of fatty acids.<ref name="ferre" /><ref name="Voet">{{cite book |last=Voet |first=Donald |author2=Judith G. Voet |author3=Charlotte W. Pratt |title=Fundamentals of Biochemistry, 2nd Edition |publisher=John Wiley and Sons, Inc. |year=2006 |pages=[https://archive.org/details/fundamentalsofbi00voet_0/page/547 547, 556] |isbn=978-0-471-21495-3 |url-access=registration |url=https://archive.org/details/fundamentalsofbi00voet_0/page/547 }}</ref>

===Regulation of fatty acid synthesis===

Acetyl-CoA is formed into [[malonyl-CoA]] by [[acetyl-CoA carboxylase]], at which point malonyl-CoA is destined to feed into the fatty acid synthesis pathway. Acetyl-CoA carboxylase is the point of regulation in saturated straight-chain fatty acid synthesis, and is subject to both [[phosphorylation]] and [[allosteric regulation]]. Regulation by phosphorylation occurs mostly in mammals, while allosteric regulation occurs in most organisms. Allosteric control occurs as feedback inhibition by palmitoyl-CoA and activation by citrate. When there are high levels of palmitoyl-CoA, the final product of saturated fatty acid synthesis, it allosterically inactivates acetyl-CoA carboxylase to prevent a build-up of fatty acids in cells. Citrate acts to activate acetyl-CoA carboxylase under high levels, because high levels indicate that there is enough acetyl-CoA to feed into the [[Krebs cycle]] and produce energy.<ref>Diwan, Joyce J. "Fatty Acid Synthesis." Rensselaer Polytechnic Institute (RPI) :: Architecture, Business, Engineering, IT, Humanities, Science. Web. 30 Apr. 2011. <{{cite web |url=http://rpi.edu/dept/bcbp/molbiochem/MBWeb/mb2/part1/fasynthesis.htm |title=Fatty Acid Synthesis |access-date=2011-05-02 |url-status=dead |archive-url=https://web.archive.org/web/20110607051537/http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb2/part1/fasynthesis.htm |archive-date=2011-06-07 }}>.</ref>

High plasma levels of [[insulin]] in the blood plasma (e.g. after meals) cause the dephosphorylation and activation of acetyl-CoA carboxylase, thus promoting the formation of malonyl-CoA from acetyl-CoA, and consequently the conversion of carbohydrates into fatty acids, while [[epinephrine]] and [[glucagon]] (released into the blood during starvation and exercise) cause the phosphorylation of this enzyme, inhibiting [[lipogenesis]] in favor of fatty acid oxidation via [[beta-oxidation]].<ref name=stryer /><ref name=Voet />

==Disorders==
Disorders of fatty acid metabolism can be described in terms of, for example, [[hypertriglyceridemia]] (too high level of [[triglyceride]]s), or other types of [[hyperlipidemia]]. These may be familial or acquired.

Familial types of disorders of fatty acid metabolism are generally classified as [[inborn errors of lipid metabolism]]. These disorders may be described as [[fatty acid oxidation disorder]]s or as a ''[[lipid storage disorder]]s'', and are any one of several [[inborn errors of metabolism]] that result from enzyme or transport protein defects affecting the ability of the body to [[oxidize]] [[fatty acid]]s in order to produce energy within muscles, liver, and other [[cell (biology)|cell]] types. When a fatty acid oxidation disorder affects the muscles, it is a [[metabolic myopathy]].

Moreover, cancer cells can display irregular fatty acid metabolism with regard to both [[fatty acid synthesis]]<ref>{{cite journal | vauthors = Ezzeddini R, Taghikhani M, Somi MH, Samadi N, Rasaee, MJ | title = Clinical importance of FASN in relation to HIF-1α and SREBP-1c in gastric adenocarcinoma | journal = Life Sciences | volume = 224 | issue = | pages = 169–176 | date = May 2019 | pmid = 30914315 | doi = 10.1016/j.lfs.2019.03.056 | s2cid = 85532042 | url = https://www.sciencedirect.com/science/article/abs/pii/S0024320519302206 | issn = | url-access = subscription }}</ref> and mitochondrial [[fatty acid oxidation]] (FAO)<ref>{{cite journal | vauthors = Ezzeddini R, Taghikhani M, Salek Farrokhi A, Somi MH, Samadi N, Esfahani A, Rasaee, MJ | title = Downregulation of fatty acid oxidation by involvement of HIF-1α and PPARγ in human gastric adenocarcinoma and its related clinical significance | journal = Journal of Physiology and Biochemistry | volume = 77 | issue = 2 | pages = 249–260 | date = May 2021 | pmid =  33730333 | doi = 10.1007/s13105-021-00791-3| s2cid = 232300877 | issn=1138-7548  }}</ref> that are involved in diverse aspects of tumorigenesis and cell growth.

==References==
{{reflist}}{{Fatty-acid metabolism disorders}}{{Lipid metabolism}}
{{MetabolismMap}}
{{Lipid metabolism enzymes}}

{{DEFAULTSORT:Fatty Acid Metabolism}}
[[Category:Metabolism]]
[[Category:Fatty acids]]
[[Category:Hepatology]]