Lingual lipase 1880909 221170984 2008-06-23T10:13:55Z DOI bot 6652755 Citation maintenance. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. {{Cleanup|date=May 2008}} {{protein | Name = Lingual Lipase | caption = Proposed crystal structure of Lingual Lipase | image = | width = | HGNCid = | Synonyms = Triacylglycerol, | AltSymbols = | EntrezGene = | OMIM = | RefSeq = | UniProt = | PDB = 4tgL | ECnumber = 3.1.1.3 | Chromosome = | Arm = | Band = | }} '''Lingual lipase''' is a member of a family of digestive [[enzyme]]s called [[lipase]]s, EC 3.1.1.3, that use the catalytic triad of [[Aspartate]] (Asp), [[Histidine]] (His), and [[Serine]] (Ser) to hydrolyze long chain [[triglycerides]] into partial [[glycerides]] and free [[fatty acids]]. The enzyme [[catalyze]]s the first reaction in the digestion of dietary lipid with diglycerides being the primary reaction product.<ref name=Hamosh>{{cite journal |author=Margit Hamos and Robert O. Scow. |title=Lingual Lipase and Its Role in the Digestion of Dietary Lipid. |journal=J Clin Ivest |volume=52 |issue=1 |pages=88–95|year=1973 |pmid= |doi=10.1172/JCI107177 |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=302230}}</ref> However, due to the unique characteristics of lingual lipase, including a pH optimum 4.5 -5.4 and its ability to catalyze reactions without [[bile salt]]s, the lipolytic activity continues through to the stomach.<ref name=Ross>{{cite journal |author=Ross W. Shepherd and Geoffrey J. Cleghorn. |title=Cystic Fibrosis: Nutritional and Intestinal Disorders. |journal= |volume= |issue= |pages=|year=1989 |pmid= |doi= |url=}}</ref> Enzyme release is signaled by [[autonomic nervous system]] after ingestion, at which time the [[serous glands]] under the circumvallate and [[foliate papillae]] on the surface of the tongue (see Figure 1) <ref name=Chandrashekar>{{cite journal |author=Javaram Chandrashekar et al. |title=The Receptors and Cells for mammalian taste. |journal=Nature |volume=444 |issue= |pages=288–294 |year=2006 |pmid= |doi=10.1038/nature05401 |url=http://www.nature.com/nature/journal/v444/n7117/full/nature05401.html }}</ref> secrete lingual lipase to the grooves of the circumvallate and foliate papillae. The [[hydrolysis]] of the dietary fats is essential for fat absorption by the small intestine, as long chain triacyglycerides cannot be absorbed, and as much as 30% of fat is hydrolyzed within 1 to 20 minutes of ingestion by lingual lipase alone.<ref name=Ross>{{cite journal |author=Ross W. Shepherd and Geoffrey J. Cleghorn. |title=Cystic Fibrosis: Nutritional and Intestinal Disorders. |journal= |volume= |issue= |pages=|year=1989 |pmid= |doi= |url=}}</ref> == Proposed Mechanism == [[Image:chimeralarge.png|thumb|Lingual Lipase|300px|right|Figure 2: Lingual Lipase with catalytic triad highlighted in center]]<!-- Deleted image removed: [[Image:chimerazoom1.png|thumb|Lingual Lipase|300px|right|Figure 3: Zoomed in view of Lingual Lipase Catalytic Triad (neon) with involved Hydrogen bonds (pink)]] --> Lingual lipase uses a catalytic triad consisting of Aspartatic Acid-203 (Asp), Histidine-257 (His), and Serine-144 (Ser), to initiate the [[hydrolysis]] of a triglyceride into a diacyglyceride and a free fatty acid. First, there are a series of [[deprotonation]]s that make the serine a better [[nucleophile]]. The [[lone pair]] on the oxygen of the serine then undergoes a [[nucleophilic addition]] to either the first or the third [[carbonyl]] of the [[triacylglycerol]]. Next, the electrons that had moved to form the carbonyl transfer back down to reform the carbonyl. Then the diacyclglycerol leaving group is protonated by His-257. Following another round of deprotonations, the lone pair on the oxygen of water undergoes a nucleophilic addition to the carbonyl that reformed in the previous step. The electrons that had moved up from the carbonyl come back down to reform it and kick off the Ser, which again induces the chain of deprotonation. The final products of the reaction are the conserved catalytic triad, a diacylglycerol and a free fatty acid. Monoacylglyceride is also present in a lower concentration and is produced following a second round of hydrolysis by the same mechanism. <!-- Deleted image removed: [[Image:finalmechanism.png|400px|Mechanism of Triglyceride Hydrolysis|{{deletable image-caption|1=Friday, 16 May 2008}}]] --> [[Image:mech2.png|400px|Mechanism of Triglyceride Hydrolysis|{{deletable image-caption|1=Friday, 16 May 2008}}]] == Lingual Lipase and Cystic Fibrosis == Patients with [[cystic fibrosis]] (CF) have an 85% chance of additionally experiencing the effects of [[exocrine pancreatic insufficiency]].<ref name=Abrams>{{cite journal |author=Cynthia K. Abrams et al. |title=Lingual Lipase in Cystic Fibrosis: Quantification of Enzyme Activity in the Upper Small Intestine of Patients with Pancreatic Insufficiency. |journal=Journal of Clinical Investigation |volume=73 |issue= |pages=374–382 |year=1984 |pmid= |doi=10.1172/JCI111222 |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=425027 }}</ref> In the most extreme cases, these patients will produce no [[pancreatic lipase]], yet even when the enzyme is completely absent, dietary fat is still absorbed.<ref name=Abrams>{{cite journal |author=Cynthia K. Abrams et al. |title=Lingual Lipase in Cystic Fibrosis: Quantification of Enzyme Activity in the Upper Small Intestine of Patients with Pancreatic Insufficiency. |journal=Journal of Clinical Investigation |volume=73 |issue= |pages=374–382 |year=1984 |pmid= |doi=10.1172/JCI111222 |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=425027 }}</ref> Studies have shown that even in these cases, lingual lipase is present in normal amounts,<ref name=Field>{{cite journal |author=R. B. Field et al. |title=Purification of Lingual Amylase from Serous Glands of Rat Tongue and Characterization of Rat Lingual Amylase and Lingual Lipase. |journal=J Dent Res |volume=68 |issue=2 |pages=239–145 |year=1989 |pmid= |doi= |url=http://jdr.iadrjournals.org/cgi/reprint/68/2/139 }}</ref> and contributes to greater than 90% of total lipase activity in [[duodenum]].<ref name=Ross>{{cite journal |author=Ross W. Shepherd and Geoffrey J. Cleghorn. |title=Cystic Fibrosis: Nutritional and Intestinal Disorders. |journal= |volume= |issue= |pages=|year=1989 |pmid= |doi= |url=}}</ref> This can be attributed to the fact that lingual lipase has a low pH optimum and can thus remain active through the stomach into the duodenum, where there is a low [[pH]] in patients with CF. It has thus been proposed that a possible treatment option for exocrine pancreatic insufficiency would be [[enzyme replacement therapy]] using lingual lipase, increasing the amount of dietary fat absorption and decreasing the risk of [[malnutrition]]. == Fat Digestion in Neonates == In the [[uterus]], the [[fetus]] is dependent on a high [[carbohydrate]] diet. After birth, fat in milk or a milk substitute becomes the major source of nutrition. Absorptive rates of dietary fat are much lower in neonates than in adults, 65-80% as compared to >95% respectively, which can be attributed to low pancreatic lipase activity.<ref name=Hamosh>{{cite journal |author=Margit Hamos and Robert O. Scow. |title=Lingual Lipase and Its Role in the Digestion of Dietary Lipid. |journal=J Clin Ivest |volume=52 |issue=1 |pages=88–95|year=1973 |pmid= |doi=10.1172/JCI107177 |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=302230}}</ref> Furthermore, milk fat is not a good substrate for pancreatic lipase. This fact, in combination with the bile salt deficiency and low pH throughout the [[gastrointestinal tract]] of the neonate, demands that lingual lipase be the main enzyme catalyzing the hydrolysis of dietary fat. This enzyme activity has been seen as early as 26 weeks [[gestational age]], with ability to hydrolyze dietary fats variable according to digestive tract maturity.<ref name=Hamosh>{{cite journal |author=Margit Hamos and Robert O. Scow. |title=Lingual Lipase and Its Role in the Digestion of Dietary Lipid. |journal=J Clin Ivest |volume=52 |issue=1 |pages=88–95|year=1973 |pmid= |doi=10.1172/JCI107177 |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=302230}}</ref> ==References== {{reflist}} [[Category:EC 3.1.1]] {{Esterases}}