View source for Biology:Lipid metabolism

{{Short description|Biological synthesis and degradation of lipids}}
'''Lipid metabolism''' is the synthesis and degradation of [[Chemistry:Lipid|lipid]]s in cells, involving the breakdown and storage of fats for energy and the synthesis of structural and functional lipids, such as those involved in the construction of [[Biology:Cell membrane|cell membrane]]s. In animals, these fats are obtained from food and are synthesized by the [[Biology:Liver|liver]].<ref name="MM_Lipid_metabolism">{{cite news | url = http://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/lipid-disorders/overview-of-lipid-metabolism|title=Overview of Lipid Metabolism|newspaper=Merck Manuals Professional Edition|access-date=2016-11-01}}</ref> Lipogenesis is the process of synthesizing these fats.<ref name="chemistryexplained.com">{{cite web | url = http://www.chemistryexplained.com/Hy-Kr/Hydrolysis.html | title = Hydrolysis – Chemistry Encyclopedia – structure, reaction, water, proteins, examples, salt, molecule | work = chemistryexplained.com | access-date = 2016-11-01 }}</ref><ref name = "Freifelder_1987">{{cite book | last1 = Freifelder | first1 = David | name-list-style = vanc | title = Molecular biology | date = 1987 | publisher = Jones and Bartlett | location = Boston | isbn = 978-0-86720-069-0 | edition = 2nd | url-access = registration | url = https://archive.org/details/molecularbiology00davi }}</ref> The majority of lipids found in the human body from ingesting food are triglycerides and [[Chemistry:Cholesterol|cholesterol]].<ref>{{cite book | last1 = Baynes | first1 = Dominiczak | name-list-style = vanc | title = Medical Biochemistry | date = 2014|publisher=Saunders, Elsevier Limited|isbn=978-1-4557-4580-7|pages=121–122}}</ref> Other types of lipids found in the body are [[Chemistry:Fatty acid|fatty acid]]s and membrane lipids. Lipid metabolism is often considered as the [[Biology:Digestion|digestion]] and absorption process of dietary fat; however, there are two sources of fats that organisms can use to obtain energy: from consumed dietary fats and from stored fat.<ref>{{cite journal | vauthors = Arrese EL, Soulages JL | title = Insect fat body: energy, metabolism, and regulation | journal = Annual Review of Entomology | volume = 55 | pages = 207–25 | date = 2010 | pmid = 19725772 | pmc = 3075550 | doi = 10.1146/annurev-ento-112408-085356 }}</ref> Vertebrates (including humans) use both sources of fat to produce [[Physics:Energy|energy]] for organs such as the [[Biology:Heart|heart]] to function.<ref name="Lehninger_2000">{{cite book | last1 = Lehninger | first1 = Albert L | first2 = David L. | last2 = Nelson | first3 = Michael M. | last3 = Cox | name-list-style = vanc | title = Lehninger Principles of Biochemistry | location = New York | publisher = Worth Publishers | year = 2000 | edition = 3rd | isbn = 978-1-57259-931-4 | url-access = registration | url = https://archive.org/details/lehningerprincip01lehn }}</ref> Since lipids are [[Chemistry:Hydrophobic effect|hydrophobic]] molecules, they need to be solubilized before their metabolism can begin. Lipid metabolism often begins with [[Chemistry:Hydrolysis|hydrolysis]],<ref>{{cite web | last = Ophardt | first = Charles E. | name-list-style = vanc  | url = http://chemistry.elmhurst.edu/vchembook/622overview.html | title = Lipid Metabolism Summary | date = 2013 | work = Virtual Chembook | publisher = Elmhurst College }}</ref> which occurs with the help of various enzymes in the digestive system.<ref name="chemistryexplained.com" /> Lipid metabolism also occurs in plants, though the processes differ in some ways when compared to animals.<ref>{{cite journal | vauthors = Wedding RT | date = May 1972 | title = Reviewed Work: Plant Lipid Biochemistry | jstor = 2430826? | journal = The New Phytologist | volume = 71 | issue = 3 | pages = 547–548 }}</ref> The second step after the hydrolysis is the absorption of the fatty acids into the [[Biology:Epithelium|epithelial cells]] of the [[Biology:Gastrointestinal wall|intestinal wall]].<ref name="Lehninger_2000" /> In the epithelial cells, fatty acids are packaged and transported to the rest of the body.<ref name="Jo_2016">{{cite journal | vauthors = Jo Y, Okazaki H, Moon YA, Zhao T | title = Regulation of Lipid Metabolism and Beyond | journal = International Journal of Endocrinology | volume = 2016 | pages = 5415767 | date = 2016 | pmid = 27293434 | pmc = 4880713 | doi = 10.1155/2016/5415767 | doi-access = free }}</ref>

Metabolic processes include lipid digestion, lipid absorption, lipid transportation, lipid storage, lipid catabolism, and lipid biosynthesis. 
Lipid catabolism is accomplished by a process known as [[Biology:Beta oxidation|beta oxidation]] which takes place in the [[Biology:Mitochondria|mitochondria]] and [[Biology:Peroxisome|peroxisome]] cell [[Biology:Organelle|organelle]]s. 

== Lipid digestion ==
[[Biology:Digestion|Digestion]] is the first step to lipid metabolism, and it is the process of breaking the triglycerides down into smaller [[Chemistry:Monoglyceride|monoglyceride]] units with the help of [[Biology:Lipase|lipase]] enzymes. Digestion of fats begin in the mouth through chemical digestion by [[Biology:Lingual lipase|lingual lipase]]. Ingested cholesterol is not broken down by the lipases and stays intact until it enters the epithelium cells of the small intestine. Lipids then continue to the stomach where chemical digestion continues by gastric lipase and mechanical digestion begins ([[Biology:Peristalsis|peristalsis]]). The majority of lipid digestion and absorption, however, occurs once the fats reach the small intestines. Chemicals from the pancreas ([[Biology:Pancreatic lipase family|pancreatic lipase family]] and [[Biology:Bile salt-dependent lipase|bile salt-dependent lipase]]) are secreted into the small intestines to help breakdown the triglycerides,<ref>{{cite book | last1 = Pelley | first1  =John W. | name-list-style = vanc | title = Elsevier's Integrated Review Biochemistry | date = 2012 | publisher = Elsevier/Mosby | location = Philadelphia | isbn = 978-0-323-07446-9 | edition = 2nd }}</ref> along with further mechanical digestion, until they are individual [[Chemistry:Fatty acid|fatty acid]] units able to be absorbed into the small intestine's [[Biology:Epithelium|epithelial cells]].<ref>{{cite book | title = Fundamentals of Biochemistry: Life at the Molecular Level | first1 = Donald | last1 = Voet | last2 = Voet | first2 = Judith G. | last3 = Pratt | first3 =  Charlotte W. | name-list-style = vanc | date = 2013 | publisher = Wiley | isbn = 978-0-470-54784-7 | edition = Fourth | location = Hoboken, NJ | oclc = 738349533 }}</ref> It is the pancreatic lipase that is responsible for signalling for the [[Chemistry:Hydrolysis|hydrolysis]] of the triglycerides into separate free fatty acids and glycerol units.

== Lipid absorption == 
[[File:2431 Lipid Absorption.jpg|thumb|Flowchart showing the lipid absorption process]]
The second step in lipid metabolism is absorption of fats. Short chain fatty acids can be absorbed in the [[Biology:Stomach|stomach]], while most absorption of fats occurs only in the [[Biology:Small intestine|small intestine]]s. Once the triglycerides are broken down into individual fatty acids and [[Chemistry:Glycerol|glycerol]]s, along with cholesterol, they will aggregate into structures called [[Biology:Micelle|micelle]]s. Fatty acids and monoglycerides leave the micelles and diffuse across the membrane to enter the intestinal epithelial cells. In the [[Biology:Cytosol|cytosol]] of epithelial cells, fatty acids and monoglycerides are recombined back into triglycerides. In the cytosol of epithelial cells, triglycerides and cholesterol are packaged into bigger particles called chylomicrons which are amphipathic structures that transport digested lipids.<ref name="Jo_2016" />   Chylomicrons will travel through the bloodstream to enter adipose and other tissues in the body.<ref name="Lehninger_2000" /><ref name="chemistryexplained.com" /><ref name="Freifelder_1987" />

== Lipid transportation ==
Due to the hydrophobic nature of [[Biology:Membrane lipid|membrane lipid]]s, triglycerides and [[Chemistry:Cholesterol|cholesterol]]s, they require special transport proteins known as lipoproteins.<ref name="MM_Lipid_metabolism" /> The amphipathic structure of lipoproteins allows the triglycerides and cholesterol to be transported through the [[Biology:Blood|blood]]. Chylomicrons are one sub-group of lipoproteins which carry the digested lipids from small intestine to the rest of the body. The varying densities between the types of lipoproteins are characteristic to what type of fats they transport.<ref>{{cite book | last = Harris | first = J. Robin | name-list-style = vanc  | year = 2009 | title = Cholesterol binding and cholesterol transport proteins: structure and function in health and disease. | location = Dordrecht | publisher = Springer | isbn = 978-90-481-8621-1 }}</ref> For example, very-low-density lipoproteins (VLDL) carry the triglycerides synthesized by our body and [[Medicine:Low-density lipoprotein|low-density lipoprotein]]s (LDL) transport cholesterol to our peripheral tissues.<ref name="Lehninger_2000" /><ref name="MM_Lipid_metabolism" /> A number of these lipoproteins are synthesized in the liver, but not all of them originate from this organ.<ref name="MM_Lipid_metabolism" />

== Lipid storage ==

Lipids are stored in white adipose tissue as triglycerides. In a lean young adult human, the mass of triglycerides stored represents about 10–20 kilograms. Triglycerides are formed from a backbone of glycerol with three fatty acids. Free fatty acids are activated into acyl-CoA and esterified to finally reach the triglyceride droplet. Lipoprotein lipase has an important role.<ref>Mechanism of Storage and Synthesis of Fatty Acids and Triglycerides in White Adipocytes | Physiology and Physiopathology of Adipose Tissue pp 101–121 | DOI: 10.1007/978-2-8178-0343-2_8</ref>

== Lipid catabolism ==
Once the chylomicrons (or other lipoproteins) travel through the tissues, these particles will be broken down by [[Biology:Lipoprotein lipase|lipoprotein]] lipase in the luminal surface of [[Biology:Endothelium|endothelial cells]] in capillaries to release triglycerides.<ref>{{cite book | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK305896/ | title = Endotext | last1=Feingold | first1 = Kenneth R. | last2 = Grunfeld | first2 = Carl | name-list-style = vanc | date = 2000 | publisher = MDText.com, Inc.| location = South Dartmouth (MA) | pmid = 26247089 | editor-last = De Groot | editor-first = Leslie J. | editor-last2 = Chrousos | editor-first2 = George | editor-last3 = Dungan | editor-first3 = Kathleen | editor-last4 = Feingold | editor-first4 = Kenneth R. | editor-last5 = Grossman | editor-first5 = Ashley | editor-last6 = Hershman | editor-first6 = Jerome M. | editor-last7 = Koch | editor-first7 = Christian | editor-last8 = Korbonits | editor-first8 = Márta | editor-last9 = McLachlan | editor-first9 = Robert | chapter = Introduction to Lipids and Lipoproteins }}</ref> Triglycerides will get broken down into fatty acids and glycerol before entering cells and remaining cholesterol will again travel through the blood to the liver.<ref name="lipidlibrary.aocs.org" />
[[File:Beta oxidation of palmitic acid.jpg|left|frameless|705x705px|<ref name="lipidlibrary.aocs.org">{{cite web|url=http://lipidlibrary.aocs.org/Biochemistry/content.cfm?ItemNumber=39187|title=Fatty Acid beta-Oxidation – AOCS Lipid Library|website=lipidlibrary.aocs.org|access-date=2017-11-28|archive-url=https://web.archive.org/web/20190121232911/http://lipidlibrary.aocs.org/Biochemistry/content.cfm?ItemNumber=39187|archive-date=2019-01-21|url-status=dead}}</ref> Breakdown of fatty acids by beta oxidation]]
In the cytosol of the cell (for example a muscle cell), the [[Chemistry:Glycerol|glycerol]] will be converted to [[Chemistry:Glyceraldehyde 3-phosphate|glyceraldehyde 3-phosphate]], which is an intermediate in the [[Biology:Glycolysis|glycolysis]], to get further oxidized and produce energy. However, the main steps of fatty acids [[Biology:Catabolism|catabolism]] occur in the [[Biology:Mitochondrion|mitochondria]].<ref name = "Scheffler_2008">{{cite book | vauthors = Scheffler IE | title = Mitochondria | date = 2008 | publisher = Wiley-Liss | location = Hoboken, N.J. | isbn = 978-0-470-04073-7 | edition = 2nd }}</ref> Long chain fatty acids (more than 14 carbon) need to be converted to [[Chemistry:Fatty acyl-CoA esters|fatty acyl-CoA]] in order to pass across the mitochondria [[Chemistry:Membrane|membrane]].<ref name="Lehninger_2000" /> [[Biology:Fatty acid metabolism|Fatty acid catabolism]] begins in the cytoplasm of cells as acyl-CoA synthetase uses the energy from cleavage of an ATP to catalyze the addition of [[Chemistry:Coenzyme A|coenzyme A]] to the fatty acid.<ref name="Lehninger_2000" /> The resulting [[Biology:Acyl-CoA|acyl-CoA]] cross the mitochondria membrane and enter the process of [[Biology:Beta oxidation|beta oxidation]]. The main products of the beta oxidation pathway are [[Chemistry:Acetyl-CoA|acetyl-CoA]] (which is used in the [[Biology:Citric acid cycle|citric acid cycle]] to produce energy), NADH and FADH.<ref name="Scheffler_2008" /> The process of beta oxidation requires the following enzymes: [[Biology:Acyl-CoA dehydrogenase|acyl-CoA dehydrogenase]], [[Biology:Enoyl-CoA hydratase|enoyl-CoA hydratase]], [[Biology:3-hydroxyacyl-CoA dehydrogenase|3-hydroxyacyl-CoA dehydrogenase]], and 3-ketoacyl-CoA thiolase.<ref name="lipidlibrary.aocs.org" /> The diagram to the left shows how fatty acids are converted into acetyl-CoA. The overall net reaction, using [[Chemistry:Palmitoyl-CoA|palmitoyl-CoA]] (16:0) as a model substrate is:

: 7 FAD + 7 NAD<sup>+</sup> + 7 CoASH + 7 H<sub>2</sub>O + H(CH<sub>2</sub>CH<sub>2</sub>)<sub>7</sub>CH<sub>2</sub>CO-SCoA → 8 CH<sub>3</sub>CO-SCoA + 7 FADH<sub>2</sub> + 7 NADH + 7 H<sup>+</sup>

== Lipid biosynthesis ==
In addition to dietary fats, storage lipids stored in the adipose tissues are one of the main sources of energy for living organisms.<ref>{{cite journal | vauthors = Choe SS, Huh JY, Hwang IJ, Kim JI, Kim JB | title = Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders | journal = Frontiers in Endocrinology | volume = 7 | pages = 30 | date = 2016-04-13 | pmid = 27148161 | pmc = 4829583 | doi = 10.3389/fendo.2016.00030 | doi-access = free }}</ref> [[Chemistry:Triglyceride|Triacylglycerols]], lipid membrane and cholesterol can be synthesized by the organisms through various pathways.

=== Membrane lipid biosynthesis ===
There are two major classes of membrane lipids: [[Biology:Glycerophospholipid|glycerophospholipid]]s and [[Biology:Sphingolipid|sphingolipid]]s. Although many different membrane lipids are synthesized in our body, pathways share the same pattern. The first step is synthesizing the backbone ([[Chemistry:Sphingosine|sphingosine]] or [[Chemistry:Glycerol|glycerol]]), the second step is the addition of fatty acids to the backbone to make phosphatidic acid. [[Biology:Phosphatidic acid|Phosphatidic acid]] is further modified with the attachment of different hydrophilic head groups to the backbone. Membrane lipid biosynthesis occurs in the [[Biology:Endoplasmic reticulum membrane protein complex|endoplasmic reticulum membrane]].<ref name="Gault_2010">{{cite book | vauthors = Gault CR, Obeid LM, Hannun YA | title = Sphingolipids as Signaling and Regulatory Molecules | chapter = An Overview of Sphingolipid Metabolism: From Synthesis to Breakdown | series = Advances in Experimental Medicine and Biology | volume = 688 | pages = 1–23 | date = 2010 | pmid = 20919643 | pmc = 3069696 | doi = 10.1007/978-1-4419-6741-1_1 | isbn = 978-1-4419-6740-4 }}</ref>

=== Triglyceride biosynthesis ===
The phosphatidic acid is also a precursor for triglyceride biosynthesis. Phosphatidic acid phosphotase catalyzes the conversion of phosphatidic acid to diacylglyceride, which will be converted to triglycerides by [[Biology:Acyltransferase|acyltransferase]]. Triglyceride biosynthesis occurs in the cytosol.<ref name="Lok_1976">{{cite journal | vauthors = Lok CM, Ward JP, van Dorp DA | title = The synthesis of chiral glycerides starting from D- and L-serine | journal = Chemistry and Physics of Lipids | volume = 16 | issue = 2 | pages = 115–22 | date = March 1976 | pmid = 1269065 | doi = 10.1016/0009-3084(76)90003-7 }}</ref>

=== Fatty acid biosynthesis ===
The precursor for fatty acids is [[Chemistry:Acetyl-CoA|acetyl-CoA]] and it occurs in the [[Biology:Cytosol|cytosol]] of the cell.<ref name="Lok_1976" /> The overall net reaction, using palmitate (16:0) as a model substrate is:

8 Acetyl-coA + 7 ATP + 14 NADPH + 6H+ → palmitate + 14 NADP+ + 6H2O + 7ADP + 7P¡

=== Cholesterol biosynthesis ===
[[Chemistry:Cholesterol|Cholesterol]] can be made from [[Chemistry:Acetyl-CoA|acetyl-CoA]] through a multiple-step pathway known as isoprenoid pathway. Cholesterols are essential because they can be modified to form different [[Biology:Hormone|hormone]]s in the body such as [[Chemistry:Progesterone (medication)|progesterone]].<ref name="Lehninger_2000" /> 70% of cholesterol biosynthesis occurs in the cytosol of liver cells.{{Citation needed|date=January 2019}}

== Lipid metabolism disorders ==
Lipid metabolism disorders (including [[Medicine:Inborn error of lipid metabolism|inborn errors of lipid metabolism]]) are illnesses where trouble occurs in breaking down or synthesizing fats (or fat-like substances).<ref name="MedlinePlus">{{cite news|url=https://medlineplus.gov/lipidmetabolismdisorders.html|title=Lipid Metabolism Disorders|publisher= [[Social:MedlinePlus|MedlinePlus]]|access-date=2016-11-20}}</ref> Lipid metabolism disorders are associated with an increase in the concentrations of plasma lipids in the blood such as LDL cholesterol, VLDL, and [[Chemistry:Triglyceride|triglyceride]]s which most commonly lead to cardiovascular diseases.<ref>{{cite book | title = Clinical Pharmacology and Drug treatment in the elderly | last=O'Malley | first = Kevin | name-list-style = vanc | publisher = Churchil Livingstone|year=1984|isbn=978-0-443-02297-5|location=Edinburgh; New York }}</ref> A good deal of the time these disorders are hereditary, meaning it's a condition that is passed along from parent to child through their genes.<ref name="MedlinePlus" /> [[Medicine:Gaucher's disease|Gaucher's disease]] (types I, II, and III), [[Medicine:Niemann–Pick disease|Niemann–Pick disease]], [[Medicine:Tay–Sachs disease|Tay–Sachs disease]], and Fabry's disease are all diseases where those afflicted can have a disorder of their body's lipid metabolism.<ref name="MM_lipid_metabolism_disorders">{{cite news|url=https://www.merckmanuals.com/home/children-s-health-issues/hereditary-metabolic-disorders/disorders-of-lipid-metabolism|title=Disorders of Lipid Metabolism|newspaper=Merck Manuals Consumer Version|access-date=2016-11-20}}</ref> Rarer diseases concerning a disorder of the lipid metabolism are sitosterolemia, Wolman's disease, Refsum's disease, and cerebrotendinous xanthomatosis.<ref name="MM_lipid_metabolism_disorders" />

== Types of lipids ==
The types of lipids involved in lipid metabolism include:
* Membrane lipids:
** [[Chemistry:Phospholipid|Phospholipid]]s: Phospholipids are a major component of the lipid bilayer of the cell membrane and are found in many parts of the body.<ref name = "Alberts_2002">{{cite book | last1 = Alberts | first1 = Bruce | last2 = Johnson | first2 = Alexander | last3 = Lewis | first3 = Julian | last4 = Raff | first4 = Martin | last5 = Roberts | first5 = Keith | last6 = Walter | first6 = Peter | name-list-style = vanc | title = Molecular Biology of the Cell | edition = 4th | publisher = Garland Science | year = 2002 | isbn = 978-0-8153-3218-3 | chapter = The Lipid Bilayer | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK26871/ }}</ref>
** [[Biology:Sphingolipid|Sphingolipid]]s: Sphingolipids are mostly found in the cell membrane of neural tissue.<ref name="Gault_2010" />
** [[Biology:Glycolipid|Glycolipid]]s: The main role of glycolipids is to maintain lipid bilayer stability and facilitate cell recognition.<ref name = "Alberts_2002" />
** [[Biology:Glycerophospholipid|Glycerophospholipid]]s: Neural tissue (including the brain) contains high amounts of glycerophospholipids.<ref name = "Alberts_2002" />
* Other types of lipids:
** [[Chemistry:Cholesterol|Cholesterol]]s: Cholesterols are the main precursors for different hormones in our body such as progesterone and testosterone. The main function of cholesterol is controlling the cell membrane fluidity.<ref name="Incardona_2000">{{cite journal | vauthors = Incardona JP, Eaton S | title = Cholesterol in signal transduction | journal = Current Opinion in Cell Biology | volume = 12 | issue = 2 | pages = 193–203 | date = April 2000 | pmid = 10712926 | doi=10.1016/s0955-0674(99)00076-9}}</ref>
** [[Biology:Steroid|Steroid]] – see also steroidogenesis: Steroids are one of the important cell signaling molecules.<ref name="Incardona_2000" />
** Triacylglycerols (fats) – see also [[Biology:Lipolysis|lipolysis]] and [[Biology:Lipogenesis|lipogenesis]]: Triacylglycerols are the major form of energy storage in human body.<ref name="MM_Lipid_metabolism" />
** Fatty acids – see also [[Biology:Fatty acid metabolism|fatty acid metabolism]]: Fatty acids are one of the precursors used for lipid membrane and cholesterol biosynthesis. They are also used for energy.
** Bile salts: Bile salts are secreted from liver and they facilitate lipid digestion in the small intestine.<ref>{{cite journal | vauthors = Russell DW | title = The enzymes, regulation, and genetics of bile acid synthesis | journal = Annual Review of Biochemistry | volume = 72 | pages = 137–74 | date = 2003 | pmid = 12543708 | doi = 10.1146/annurev.biochem.72.121801.161712 }}</ref>
** Eicosanoids: Eicosanoids are made from fatty acids in the body and they are used for [[Biology:Cell signaling|cell signaling]].<ref>{{cite journal | vauthors = Williams KI, Higgs GA | title = Eicosanoids and Inflammation | journal = The Journal of Pathology | date = October 1988 | volume = 156 | issue = 2 | pages = 101–110 | doi = 10.1002/path.1711560204 | pmid = 3058912 | s2cid = 34803631 | doi-access = free }}</ref>
** [[Biology:Ketone bodies|Ketone bodies]]: Ketone bodies are made from fatty acids in the liver. Their function is to produce energy during periods of starvation or low food intake.<ref name="Lehninger_2000" />

== References ==
{{Reflist|32em}}

{{MeshName|Lipid+metabolism}}

{{Metabolism}}
{{MetabolismMap}}
{{Lipid metabolism enzymes}}
{{Eicosanoid metabolism enzymes}}
{{Glycolipid/sphingolipid metabolism enzymes}}
{{Ketone and cholesterol metabolism enzymes}}


[[Category:Lipids]]
[[Category:Metabolism]]

{{Sourceattribution|Lipid metabolism}}