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Lactase () is an enzyme produced by many organisms and is essential to the complete digestion of whole milk. It breaks down the sugar lactose into its component parts, galactose and glucose, simple sugars that can be absorbed into the bloodstream through an animal's intestines. A lactase is a type of β-galactosidase because it breaks down the β-glycosidic bond in D-lactose. The chemical reaction it catalyzes is:
The only human gene encoding a lactase is LCT or lactase-phlorizin hydrolase (alternative symbol LPH). LCT has a lactase protein domain and a phlorizin hydrolase domain. It is encoded on chromosome 2. Lactase is found in the brush border of the small intestine of humans and other mammals. People without the mutation allowing production of functional LCT to continue past infancy may experience the symptoms of lactose intolerance after consuming .
Microbial β-galactosidases that can hydrolyze lactose (i.e. a lactase in the broader sense) can be purchased as a food supplement and is added to milk to produce "lactose-free" milk products. This enzyme can directly break down lactose when added to dairy. Some versions can survive passage through the human stomach and break down lactose in any ingested food before it reaches the colon.
Mature human lactase consists of a single 160-kDa polypeptide chain that localizes to the brush border membrane of intestinal epithelial cells. It is oriented with the N-terminus outside the cell and the C-terminus in the cytosol. LPH contains two catalytic glutamic acid sites. In the human enzyme, the lactase activity has been connected to Glu-1749, while Glu-1273 is the site of phlorizin hydrolase function.
Some population segments exhibit lactase persistence resulting from a mutation that is postulated to have occurred 5,000–10,000 years ago, coinciding with the rise of cattle domestication. This mutation has allowed almost half of the world's population to metabolize lactose without symptoms. Studies have linked the occurrence of lactase persistence to two different single-nucleotide polymorphisms about 14 and 22 kilobases upstream of the 5'-end of the LPH gene. Both mutations, C→T at position -13910 and G→ A at position -22018, have been independently linked to lactase persistence.
The lactase promoter is 150 base pairs long and is located upstream of the site of transcription initiation. The sequence is highly conserved in mammals, suggesting that critical cis-transcriptional regulators are located nearby. Cdx-2, HNF-1α, and GATA have been identified as transcription factors. Studies of hypolactasia onset have demonstrated that despite polymorphisms, little difference exists in lactase expression in infants, showing that the mutations become increasingly relevant during development. Developmentally regulated DNA-binding proteins may down-regulate transcription or destabilize mRNA transcripts, causing decreased LPH expression after weaning.
Substrate modification studies have demonstrated that the 3′-OH and 2′-OH moieties on the galactopyranose ring are essential for recognition and hydrolysis by the mammalian lactase. The 3′-hydroxy group is involved in initial binding to the substrate while the 2′- group is not necessary for recognition but needed in subsequent steps. This is demonstrated by the fact that a 2-deoxy analog is an effective competitive inhibitor (Ki = 10mM). Elimination of specific hydroxyl groups on the glucopyranose moiety does not eliminate catalysis.
The temperature optimum for human lactase is about 37 °C and the pH optimum is 6.
As mentioned earlier, lactase is an enzyme that some people are unable to produce in their small intestine. Without lactase, lactose-intolerant people pass the lactose undigested to the colon where bacteria break it down, creating carbon dioxide which leads to bloating and flatulence. The commercial forms of lactase can break down lactose when they are either added to food or put in the human digestive tract.
Technology to produce lactose-free milk, ice cream, and yogurt was developed by the USDA Agricultural Research Service in 1985. Lactase from select species of mold are considered GRAS by the US FDA; as a result, they are allowed to be added to food in limited quantities as a processing aid. This is one of the primary commercial uses of lactase.
Commercial lactase is used as a medication for lactose intolerance. Since it is an enzyme, its function can be inhibited by the acidity of the stomach. However, it is packaged in an acid-proof tablet, allowing the enzyme to pass through the stomach intact and remain in the small intestine. In the small intestine it can act on ingested lactose molecules, allowing the body to absorb the digested sugar which would otherwise cause cramping and diarrhea. Since the enzyme is not absorbed, it is excreted.
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