Lingual lipase is a member of a family of digestive

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

s called

triacylglycerol lipase The enzyme Triacylglycerol lipase (also Triglyceride lipase, EC 3.1.1.3;systematic name triacylglycerol acylhydrolase) catalyses the hydrolysis of ester linkages of triglycerides: : triacylglycerol + H2O diacylglycerol + a carboxylate These ...

s, EC 3.1.1.3, that use the

catalytic triad A catalytic triad is a set of three coordinated amino acids that can be found in the active site of some enzymes. Catalytic triads are most commonly found in hydrolase and transferase enzymes (e.g. proteases, amidases, esterases, acylases, lip ...

aspartate Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the de ...

, and

serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...

to hydrolyze medium and long-chain

triglycerides A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''tri-'' and ''glyceride''). Triglycerides are the main constituents of body fat in humans and other vertebrates, as we ...

into partial glycerides and free

fatty acids In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...

. The enzyme, released into the mouth along with the saliva,

catalyze Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

s the first reaction in the digestion of dietary lipid, with diglycerides being the primary reaction product. 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 Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Prima ...

s, the lipolytic activity continues through to the stomach. Enzyme release is signaled by

autonomic nervous system The autonomic nervous system (ANS), formerly referred to as the vegetative nervous system, is a division of the peripheral nervous system that supplies viscera, internal organs, smooth muscle and glands. The autonomic nervous system is a control ...

after ingestion, at which time the

serous glands Serous glands secrete serous fluid. They contain serous acini, a grouping of serous cells that secrete serous fluid, isotonic with blood plasma, that contains enzymes such as alpha-amylase. Serous glands are most common in the parotid gland and ...

under the circumvallate and foliate

lingual papilla Lingual papillae (singular papilla) are small structures on the upper surface of the tongue that give it its characteristic rough texture. The four types of papillae on the human tongue have different structures and are accordingly classified as c ...

e on the surface of the tongue secrete lingual lipase to the grooves of the circumvallate and foliate papillae, co-localized with fat taste receptors. The

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

of the dietary fats is essential for fat absorption by the small intestine, as long chain triacylglycerides cannot be absorbed, and as much as 30% of fat is hydrolyzed within 1 to 20 minutes of ingestion by lingual lipase alone. Lingual lipase, together with

gastric lipase The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach ...

, comprise the two acidic lipases.

Proposed mechanism

Lingual lipase uses a catalytic triad consisting of aspartic acid-203 (Asp), histidine-257 (His), and serine-144 (Ser), to initiate the

of a triglyceride into a diacylglyceride and a free fatty acid. First, there is a series of

deprotonation Deprotonation (or dehydronation) is the removal (transfer) of a proton (or hydron, or hydrogen cation), (H+) from a Brønsted–Lowry acid in an acid–base reaction.Henry Jakubowski, Biochemistry Online Chapter 2A3, https://employees.csbsju.ed ...

s that make the serine a better

nucleophile In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...

. The

lone pair In chemistry, a lone pair refers to a pair of valence electrons that are not shared with another atom in a covalent bondIUPAC ''Gold Book'' definition''lone (electron) pair''/ref> and is sometimes called an unshared pair or non-bonding pair. Lone ...

on the oxygen of the serine then undergoes a

nucleophilic addition In organic chemistry, a nucleophilic addition reaction is an addition reaction where a chemical compound with an electrophilic double or triple bond reacts with a nucleophile, such that the double or triple bond is broken. Nucleophilic additions di ...

to either the first or the third

carbonyl In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a ...

of the

triacylglycerol A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''tri-'' and ''glyceride''). Triglycerides are the main constituents of body fat in humans and other vertebrates, as we ...

. Next, the electrons that had moved to form the carbonyl transfer back down to reform the carbonyl. Then the diacylglycerol 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 Monoglycerides (also: acylglycerols or monoacylglycerols) are a class of glycerides which are composed of a molecule of glycerol linked to a fatty acid via an ester bond. As glycerol contains both primary and secondary alcohol groups two differen ...

is also present in a lower concentration and is produced following a second round of hydrolysis by the same mechanism. It acts on tryglicerides to help breakdown food as a part of saliva composition.

Cystic fibrosis

Patients with

cystic fibrosis Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. O ...

(CF) have an 85% chance of additionally experiencing the effects of

exocrine pancreatic insufficiency Exocrine pancreatic insufficiency (EPI) is the inability to properly digest food due to a lack of digestive enzymes made by the pancreas. EPI is found in humans afflicted with cystic fibrosis and Shwachman–Diamond syndrome, and is common in ...

. In the most extreme cases, these patients will produce no

pancreatic lipase Triglyceride lipases () are a family of lipolytic enzymes that hydrolyse ester linkages of triglycerides. Lipases are widely distributed in animals, plants and prokaryotes. At least three tissue-specific isozymes exist in higher vertebrates, p ...

, 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, and contributes to greater than 90% of total lipase activity in

duodenum The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear, and the terms anterior intestine or proximal intestine m ...

. 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 Enzyme replacement therapy (ERT) is a medical treatment which replaces an enzyme that is deficient or absent in the body. Usually, this is done by giving the patient an intravenous (IV) infusion of a solution containing the enzyme. ERT is availab ...

using lingual lipase, increasing the amount of dietary fat absorption and decreasing the risk of

malnutrition Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues a ...

. The proposed mechanism of lingual lipase preferentially cleaving short and medium chain triacylglycerols provides a means for absorption without the need for

micelle A micelle () or micella () (plural micelles or micellae, respectively) is an aggregate (or supramolecular assembly) of surfactant amphipathic lipid molecules dispersed in a liquid, forming a colloidal suspension (also known as associated collo ...

formation and

chylomicrons Chylomicrons (from the Greek χυλός, chylos, meaning ''juice'' (of plants or animals), and micron, meaning ''small particle''), also known as ultra low-density lipoproteins (ULDL), are lipoprotein particles that consist of triglycerides (85 ...

. Short and medium chain free fatty acids can be absorbed directly through the mucosal cells into the blood stream without further packaging and hence play a crucial role in nutrition for CF patients (and neonates).

Fat digestion in neonates

In the

uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uter ...

, the

fetus A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal deve ...

is dependent on a high-

carbohydrate In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or ma ...

diet, and lingual as well as gastric lipases are present in the fetus from 26 weeks of gestation on. After birth, fat in mother's milk or a

milk substitute A milk substitute is any substance that resembles milk and can be used in the same ways as milk. Such substances may be variously known as non-dairy beverage, nut milk, grain milk, legume milk, mock milk and alternative milk. For adults, milk ...

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 The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...

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 In obstetrics, gestational age is a measure of the age of a pregnancy which is taken from the beginning of the woman's last menstrual period (LMP), or the corresponding age of the gestation as estimated by a more accurate method if available. Suc ...

, with ability to hydrolyze dietary fats variable according to digestive tract maturity.

References

{{Portal bar, Biology, border=no EC 3.1.1