Mannose is a simple sugar, a close relative of glucose, with specific functions in human health. Though less widely known, it is a non-essential nutrient because the body can produce it from glucose. The metabolism of mannose is important for a process that modifies certain proteins after they are created.
Sources of Mannose
The body acquires mannose through two primary routes: absorption from food and internal creation. Many polysaccharides and glycoproteins in our diet yield mannose when broken down. Foods containing this sugar include fruits like cranberries, peaches, and apples, as well as plant products such as aloe vera.
When dietary intake is insufficient, the body has its own mechanism for producing mannose. This internal synthesis pathway converts glucose into mannose as needed. Specifically, mannose is generated from fructose-6-phosphate, an intermediate molecule in the metabolism of glucose.
How the Body Uses Mannose
Once mannose enters a cell, it is directed into a specific metabolic pathway. The first step involves an enzyme called hexokinase, which attaches a phosphate group to the mannose molecule, transforming it into mannose-6-phosphate (M-6-P). This phosphorylation acts like a trap, preventing the sugar from leaving the cell and preparing it for subsequent reactions. From this point, the M-6-P molecule faces two potential fates.
The majority of intracellular mannose, over 95% in mammals, is channeled toward energy production. The enzyme phosphomannose isomerase (MPI) converts M-6-P into fructose-6-phosphate. This molecule is an intermediate in glycolysis, the pathway for breaking down sugars to generate cellular energy, allowing mannose to serve as a fuel source.
The second path for M-6-P leads to the creation of complex molecules. The enzyme phosphomannomutase 2 (PMM2) converts M-6-P into mannose-1-phosphate (M-1-P). This M-1-P then reacts with guanosine triphosphate (GTP) to form guanosine diphosphate-mannose (GDP-mannose), the activated form of the sugar used for structural functions.
The Importance of Glycosylation
The main purpose for creating GDP-mannose is a process called glycosylation. This is a post-translational modification, meaning it occurs after a protein has been built. During N-linked glycosylation, chains of sugar molecules, known as glycans, are attached to proteins, and mannose is a frequent component of these chains.
These attached sugar structures are not merely decorative; they alter the protein’s function and properties. This process helps ensure proteins fold into their correct three-dimensional shapes for proper operation. The glycans also act as quality control markers, helping to distinguish correctly folded proteins from misfolded ones that need to be removed.
These sugar modifications also play a part in how cells interact with their environment. Glycoproteins, proteins decorated with these sugar chains, are often found on the cell surface. They function as identification markers recognized by the immune system, helping it distinguish the body’s own cells from foreign invaders.
Disorders of Mannose Metabolism
Failures in the mannose metabolic pathway can lead to serious health consequences known as Congenital Disorders of Glycosylation (CDGs). These are genetic diseases caused by mutations in genes for glycosylation enzymes. The most common is PMM2-CDG, which results from a deficiency in the enzyme phosphomannomutase 2.
A defect in this enzyme disrupts the production of GDP-mannose, leading to a systemic shortage of properly formed glycoproteins, a state known as hypoglycosylation. This lack of correctly glycosylated proteins can affect numerous organ systems, with the nervous system often being vulnerable. The clinical presentation of these disorders can be diverse, reflecting the importance of glycosylation for normal cellular function.
Mannose Supplementation and Health
Mannose has gained attention as a dietary supplement, most notably as D-mannose for managing urinary tract infections (UTIs). Its proposed mechanism in this context is distinct from its internal metabolic role in glycosylation.
The primary cause of most UTIs is the bacterium Escherichia coli (E. coli), which initiates an infection by adhering to the inner walls of the urinary tract. When a person consumes D-mannose supplements, a portion is absorbed, passes through the bloodstream, and is then excreted into the urine.
Once in the urinary tract, D-mannose is believed to interfere with the bacteria’s ability to stick to the bladder walls. E. coli have surface structures that bind to mannose-containing molecules on human cells. By flooding the urine with free D-mannose, the supplement provides an alternative target for the bacteria, preventing them from latching onto the urinary tract lining so they can be flushed out.