Lingual lipase

protein
Name = Lingual Lipase
caption = Proposed crystal structure of Lingual Lipase


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HGNCid =
Synonyms = Triacylglycerol,
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EntrezGene =
OMIM =
RefSeq =
UniProt =
PDB = 4tgL
ECnumber = 3.1.1.3
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Band =

Lingual lipase is a member of a family of digestive enzymes called lipases, 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 catalyzes the first reaction in the digestion of dietary lipid with diglycerides being the primary reaction product.cite journal |author=Hamosh M, Scow RO |title=Lingual lipase and its role in the digestion of dietary lipid |journal=J. Clin. Invest. |volume=52 |issue=1 |pages=88–95 |year=1973 |month=Jan |pmid=4682389 |pmc=302230 |doi=10.1172/JCI107177 |url=] 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 salts, the lipolytic activity continues through to the stomach.cite book |author=Cleghorn, Geoffrey J.; Shepherd, Ross W. |title=Cystic fibrosis: nutritional and intestinal disorders |publisher=CRC Press |location=Boca Raton |year=1989 |pages= |isbn=0-8493-6954-1 |oclc= |doi= |accessdate=] 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) cite journal |author=Chandrashekar J, Hoon MA, Ryba NJ, Zuker CS |title=The receptors and cells for mammalian taste |journal=Nature |volume=444 |issue=7117 |pages=288–94 |year=2006 |month=Nov |pmid=17108952 |doi=10.1038/nature05401 |url=http://www.nature.com/nature/journal/v444/n7117/full/nature05401.html ] 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.

Proposed Mechanism

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 deprotonations 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.

Lingual Lipase and Cystic Fibrosis

Patients with cystic fibrosis (CF) have an 85% chance of additionally experiencing the effects of exocrine pancreatic insufficiency.cite journal |author=Abrams CK, Hamosh M, Hubbard VS, Dutta SK, Hamosh P |title=Lingual lipase in cystic fibrosis. Quantitation of enzyme activity in the upper small intestine of patients with exocrine pancreatic insufficiency |journal=J. Clin. Invest. |volume=73 |issue=2 |pages=374–82 |year=1984 |month=Feb |pmid=6699170 |pmc=425027 |doi=10.1172/JCI111222 |url=] 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. Studies have shown that even in these cases, lingual lipase is present in normal amounts,cite journal |author=Field RB, Spielman AI, Hand AR |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=139–45 |year=1989 |month=Feb |pmid=2465330 |doi= |url=http://jdr.iadrjournals.org/cgi/reprint/68/2/139 ] and contributes to greater than 90% of total lipase activity in duodenum. 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. 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.

References