Editing Fatty acid (section)

==Production==

===Industrial===
Fatty acids are usually produced industrially by the [[hydrolysis]] of [[triglyceride]]s, with the removal of [[glycerol]] (see [[oleochemical]]s). [[Phospholipid]]s represent another source. Some fatty acids are produced synthetically by [[carbonylation|hydrocarboxylation]] of alkenes.<ref name="Ullmann Fatty Acids">{{Ullmann|doi=10.1002/14356007.a10_245.pub2|title=Fatty Acids|date=2006|last1=Anneken|first1=David J.|last2=Both|first2=Sabine|last3=Christoph|first3=Ralf|last4=Fieg|first4=Georg|last5=Steinberner|first5=Udo|last6=Westfechtel|first6=Alfred}}</ref>

===By animals===
{{main|Fatty acid synthesis}}
In animals, fatty acids are formed from carbohydrates predominantly in the [[liver]], [[adipose tissue]], and the [[mammary gland]]s during lactation.<ref name=stryer>{{cite book |last1= Stryer |first1= Lubert | title=Biochemistry |chapter= Fatty acid metabolism. |edition= 4th |location= New York |publisher= W. H. Freeman and Company|date= 1995 |pages= 603–628 |isbn= 978-0-7167-2009-6 }}</ref>

Carbohydrates are converted into [[Pyruvic acid|pyruvate]] by [[glycolysis]] as the first important step in the conversion of carbohydrates into fatty acids.<ref name=stryer /> Pyruvate is then decarboxylated to form [[acetyl-CoA]] in the [[mitochondrion]]. However, this acetyl CoA needs to be transported into [[cytosol]] where the synthesis of fatty acids occurs. This cannot occur directly. To obtain cytosolic acetyl-CoA, [[Citric acid|citrate]] (produced by the condensation of acetyl-CoA with [[Oxaloacetic acid|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 the mitochondrion as [[malate]].<ref name= ferre>{{cite journal | doi = 10.1159/000100426 | title = SREBP-1c Transcription Factor and Lipid Homeostasis: Clinical Perspective | journal = Hormone Research | year = 2007 | first1 = P. | last1 = Ferre |first2=F. |last2=Foufelle | volume = 68 | issue = 2 | pages = 72–82| doi-broken-date = 1 November 2024 | pmid = 17344645 | 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 |last1=Voet |first1=Donald |first2=Judith G. |last2=Voet |first3=Charlotte W. |last3=Pratt |title=Fundamentals of Biochemistry |edition=2nd |publisher=John Wiley and Sons |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>

Malonyl-CoA is then involved in a repeating series of reactions that lengthens the growing fatty acid chain by two carbons at a time. Almost all natural fatty acids, therefore, have even numbers of carbon atoms. When synthesis is complete the free fatty acids are nearly always combined with glycerol (three fatty acids to one glycerol molecule) to form [[triglyceride]]s, the main storage form of fatty acids, and thus of energy in animals. However, fatty acids are also important components of the [[phospholipid]]s that form the [[phospholipid bilayers]] out of which all the membranes of the cell are constructed (the [[cell wall]], and the membranes that enclose all the [[organelle]]s within the cells, such as the [[Cell nucleus|nucleus]], the [[Mitochondrion|mitochondria]], [[endoplasmic reticulum]], and the [[Golgi apparatus]]).<ref name=stryer />

The "uncombined fatty acids" or "free fatty acids" found in the circulation of animals come from the breakdown (or [[lipolysis]]) of stored triglycerides.<ref name=stryer /><ref>{{cite journal | last1 = Zechner | first1 = R. | last2 = Strauss | first2 = J. G. | last3 = Haemmerle | first3 = G. | last4 = Lass | first4 = A. | last5 = Zimmermann | first5 = R. | year = 2005 | title = Lipolysis: pathway under construction | journal = Curr. Opin. Lipidol. | volume = 16 | issue = 3| pages = 333–340 | doi = 10.1097/01.mol.0000169354.20395.1c | pmid = 15891395 | s2cid = 35349649 }}</ref> Because they are insoluble in water, these fatty acids are transported bound to plasma [[albumin]]. The levels of "free fatty acids" in the blood are limited by the availability of albumin binding sites. They can be taken up from the blood by all cells that have mitochondria (with the exception of the cells of the [[central nervous system]]). Fatty acids can only be broken down in mitochondria, by means of [[beta-oxidation]] followed by further combustion in the [[citric acid cycle]] to CO{{sub|2}} and water. Cells in the central nervous system, although they possess mitochondria, cannot take free fatty acids up from the blood, as the [[blood–brain barrier]] is impervious to most free fatty acids,{{citation needed|date=June 2016}} excluding [[short-chain fatty acid]]s and [[medium-chain fatty acid]]s.<ref name="SCFA MCT-mediated BBB passage - 2005 review">{{cite journal | vauthors = Tsuji A | title = Small molecular drug transfer across the blood–brain barrier via carrier-mediated transport systems | journal = NeuroRx | volume = 2 | issue = 1 | pages = 54–62 | year = 2005 | pmid = 15717057 | pmc = 539320 | doi = 10.1602/neurorx.2.1.54 | quote = Uptake of valproic acid was reduced in the presence of medium-chain fatty acids such as hexanoate, octanoate, and decanoate, but not propionate or butyrate, indicating that valproic acid is taken up into the brain via a transport system for medium-chain fatty acids, not short-chain fatty acids.&nbsp;... Based on these reports, valproic acid is thought to be transported bidirectionally between blood and brain across the BBB via two distinct mechanisms, monocarboxylic acid-sensitive and medium-chain fatty acid-sensitive transporters, for efflux and uptake, respectively.}}</ref><ref name="SCFA MCT-mediated BBB passage - 2014 review">{{cite journal | vauthors = Vijay N, Morris ME | title = Role of monocarboxylate transporters in drug delivery to the brain | journal = Curr. Pharm. Des. | volume = 20 | issue = 10 | pages = 1487–98 | year = 2014 | pmid = 23789956 | pmc = 4084603 | doi = 10.2174/13816128113199990462| quote = Monocarboxylate transporters (MCTs) are known to mediate the transport of short chain monocarboxylates such as lactate, pyruvate and butyrate.&nbsp;... MCT1 and MCT4 have also been associated with the transport of short chain fatty acids such as acetate and formate which are then metabolized in the astrocytes [78].}}</ref> These cells have to manufacture their own fatty acids from carbohydrates, as described above, in order to produce and maintain the phospholipids of their cell membranes, and those of their organelles.<ref name=stryer />

====Variation between animal species====
Studies on the [[cell membrane]]s of [[mammal]]s and [[reptile]]s discovered that mammalian cell membranes are composed of a higher proportion of polyunsaturated fatty acids ([[docosahexaenoic acid|DHA]], [[omega-3 fatty acid|omega−3 fatty acid]]) than [[reptile]]s.<ref name=hulb1999/> Studies on bird fatty acid composition have noted similar proportions to mammals but with 1/3rd less omega−3 fatty acids as compared to [[omega-6 fatty acid|omega−6]] for a given body size.<ref name=hulb2002/> This fatty acid composition results in a more fluid cell membrane but also one that is permeable to various ions ({{chem2|H+}} & {{chem2|Na+}}), resulting in cell membranes that are more costly to maintain. This maintenance cost has been argued to be one of the key causes for the high metabolic rates and concomitant [[warm-blooded]]ness of mammals and birds.<ref name=hulb1999/> However polyunsaturation of cell membranes may also occur in response to chronic cold temperatures as well. In [[fish]] increasingly cold environments lead to increasingly high cell membrane content of both monounsaturated and polyunsaturated fatty acids, to maintain greater membrane fluidity (and functionality) at the lower [[temperature]]s.<ref name=hulb2003xa/><ref name=rayn1991/>