Lactase, formally known as lactase-phlorizin hydrolase (LPH), is a complex protein that serves a singular function in mammalian digestion. This enzyme acts as a biological catalyst, initiating a chemical reaction that breaks down the disaccharide lactose, a sugar found predominantly in milk. The breakdown of this larger molecule produces two simpler sugar units: glucose and galactose. This enzymatic process is the fundamental step required for the body to absorb and utilize milk sugar as an energy source.
Molecular Structure and Location
The lactase enzyme is structurally classified as a transmembrane protein, meaning it is embedded directly within the cellular membrane. Specifically, it resides on the brush border membrane of the enterocytes, the absorptive cells lining the small intestine. This strategic positioning allows the enzyme to interact with dietary lactose as soon as it enters the intestinal lumen.
The mature human lactase protein is an ectoenzyme anchored to the membrane by a single hydrophobic segment near its C-terminus, leaving the bulk of the protein projecting outward into the intestinal space. It is derived from a larger precursor protein that undergoes processing before reaching its final destination. The active form of the enzyme is a homodimer, composed of two identical protein subunits, each weighing approximately 160 kilodaltons.
Each subunit of the mature lactase enzyme contains two distinct catalytic sites, reflecting its dual name, lactase-phlorizin hydrolase. One site is specialized for the hydrolysis of lactose, while the other handles the breakdown of compounds like phlorizin. The lactase activity has been traced to a specific glutamic acid residue (Glu-1749) within the protein structure.
The Hydrolysis Mechanism
The function of lactase is to perform a hydrolysis reaction, a chemical process that uses water to cleave a larger molecule apart. Lactose is a disaccharide, composed of galactose linked to glucose by a \(\beta\)-glycosidic bond. This bond is too stable for the body to break without enzymatic assistance, and the lactose molecule is too large to be directly absorbed by the intestinal lining.
The process begins when the lactose substrate enters the active site of the lactase enzyme, which acts like a molecular pocket shaped to bind the sugar. Once bound, the lactase enzyme facilitates a double displacement reaction to break the glycosidic bond. A specific amino acid residue, acting as a nucleophile, attacks the galactosyl carbon of the lactose molecule.
This initial attack cleaves the bond between the glucose and galactose units, releasing the glucose molecule. The galactose unit remains temporarily attached to the enzyme’s active site. The second step involves a molecule of water entering the active site and displacing the covalently bound galactose unit.
The water molecule acts as a second nucleophile, releasing the galactose and restoring the enzyme to its original, unbound state. This use of water is why the reaction is termed hydrolysis. The final products—glucose and galactose—are small enough to be taken up by specialized transport proteins and moved into the bloodstream.
The successful breakdown of lactose into these two monosaccharides is the fundamental goal of the enzyme’s function. If the enzyme is absent or inactive, the intact lactose molecule continues its journey through the digestive tract. This prevents nutrient absorption and causes the sugar to pass into the large intestine for fermentation by gut bacteria.
Genetic Regulation and Lactase Persistence
The production of the lactase enzyme is controlled by the \(LCT\) gene, located on chromosome 2 in humans. Regulation of this gene is a classic example of a developmental switch, where expression levels change dramatically after infancy. In most mammals and a majority of the human population, the \(LCT\) gene is highly active during nursing and then undergoes a significant reduction in activity after weaning.
This reduction in enzyme production is termed lactase non-persistence, considered the ancestral trait. The decline, often up to 90%, is not due to a change in the \(LCT\) gene itself but is governed by a regulatory element acting as a genetic switch. This regulatory region is located far upstream of the \(LCT\) gene, nestled within the sequence of a neighboring gene called \(MCM6\).
Lactase persistence, the ability to maintain high levels of lactase activity into adulthood, results from specific single-nucleotide polymorphisms (SNPs) in this \(MCM6\) regulatory region. The most widely studied variant is a C-to-T change at position -13910, approximately 14 kilobases upstream of the \(LCT\) gene. The presence of the T allele prevents the typical age-dependent downregulation.
The persistence trait is a relatively recent evolutionary adaptation, strongly correlated with populations that have a long history of cattle domestication and milk consumption. These genetic variations in the \(MCM6\) enhancer region ensure that transcription factors necessary for \(LCT\) gene expression continue to bind effectively, allowing for the continuous synthesis of the lactase enzyme.