MANNOSE, PACKAGED AS THE NUTRITIONAL SUPPLEMENT "D-MANNOSE", IS A SUGAR MONOMER OF THE ALDOHEXOSE SERIES OF CARBOHYDRATES . IT IS A C-2 EPIMER OF GLUCOSE . MANNOSE IS IMPORTANT IN HUMAN METABOLISM, ESPECIALLY IN THE GLYCOSYLATION OF CERTAIN PROTEINS. SEVERAL CONGENITAL DISORDERS OF GLYCOSYLATION ARE ASSOCIATED WITH MUTATIONS IN ENZYMES INVOLVED IN MANNOSE METABOLISM.[1]
MANNOSE IS NOT AN ESSENTIAL NUTRIENT; IT CAN BE PRODUCED IN THE HUMAN BODY FROM GLUCOSE, OR CONVERTED INTO GLUCOSE. MANNOSE PROVIDES 2-5 KCAL/G. IT IS PARTIALLY EXCRETED IN THE URINE.
METABOLISM OF COMMON MONOSACCHARIDES AND RELATED REACTIONS
WHILE MUCH OF THE MANNOSE USED IN GLYCOSYLATION IS BELIEVED TO BE DERIVED FROM GLUCOSE, IN CULTURED HEPATOMA CELLS (CANCEROUS CELLS FROM THE LIVER), MOST OF THE MANNOSE FOR GLYCOPROTEIN BIOSYNTHESIS COMES FROM EXTRACELLULAR MANNOSE, NOT GLUCOSE.[2] MANY OF THE GLYCOPROTEINS PRODUCED IN THE LIVER ARE SECRETED INTO THE BLOODSTREAM, SO DIETARY MANNOSE IS DISTRIBUTED THROUGHOUT THE BODY. [3]
MANNOSE IS PRESENT IN NUMEROUS GLYCOCONJUGATES INCLUDING N-LINKED GLYCOSYLATION OF PROTEINS. C-MANNOSYLATION IS ALSO ABUNDANT AND CAN BE FOUND IN COLLAGEN-LIKE REGIONS.
THE DIGESTION OF MANY POLYSACCHARIDES AND GLYCOPROTEINS YIELDS MANNOSE, WHICH IS PHOSPHORYLATED BY HEXOKINASE TO GENERATE MANNOSE-6-PHOSPHATE. MANNOSE-6-PHOSPHATE IS CONVERTED TO FRUCTOSE-6-PHOSPHATE , BY THE ENZYME PHOSPHOMANNOSE ISOMERASE , AND THEN ENTERS THE GLYCOLYTIC PATHWAY OR IS CONVERTED TO GLUCOSE-6-PHOSPHATE BY THE GLUCONEOGENIC PATHWAY OF HEPATOCYTES .
MANNOSE IS A DOMINANT MONOSACCHARIDE IN N-LINKED GLYCOSYLATION, WHICH IS A POST-TRANSLATIONAL MODIFICATION OF PROTEINS. IT IS INITIATED BY THE EN BLOC TRANSFER ON GLC3MAN9GLCNAC2 TO NASCENT GLYCOPROTEINS IN THE ENDOPLASMIC RETICULUM IN A CO-TRANSLATIONAL MANNER AS THE PROTEIN ENTERED THROUGH THE TRANSPORT SYSTEM. GLUCOSE IS HYDROLYZED ON FULLY FOLDED PROTEIN AND THE MANNOSE MOIETIES ARE HYDROLYZED BY ER AND GOLGI-RESIDENT MANNOSIDASES. TYPICALLY, MATURE HUMAN GLYCOPROTEINS ONLY CONTAIN THREE MANNOSE RESIDUES BURIED UNDER SEQUENTIAL MODIFICATION BY GLCNAC, GALACTOSE, AND SIALIC ACID. THIS IS IMPORTANT, AS THE INNATE IMMUNE SYSTEM IN MAMMALS IS GEARED TO RECOGNISE EXPOSED MANNOSE RESIDUES. THIS ACTIVITY IS DUE TO THE PREVALENCE OF MANNOSE RESIDUES, IN THE FORM OF MANNANS, ON THE SURFACES OF YEASTS. THE HUMAN IMMUNODEFICIENCY VIRUS DISPLAYS CONSIDERABLE AMOUNT OF MANNOSE RESIDUES DUE TO THE TIGHT CLUSTERING OF GLYCANS IN ITS VIRAL SPIKE.[4] [5] THESE MANNOSE RESIDUES ARE THE TARGET FOR BROADLY NEUTRALIZING ANTIBODIES.[6]
USES
MANNOSE (D-MANNOSE) IS USED AS A NUTRITIONAL SUPPLEMENT TO PREVENT RECURRENT URINARY TRACT INFECTIONS. [8]
MANNOSE PTS PERMEASE
MANNOSE XYZ PERMEASE COMPLEX: ENTRY OF PEP WHICH DONATES A HIGH ENERGY PHOSPHATE THAT GETS PASSED THROUGH THE TRANSPORTER SYSTEM AND EVENTUALLY ASSIST IN THE ENTRY OF MANNOSE (IN THIS EXAMPLE OTHERWISE IT WOULD ANY HEXOSE SUGAR) AND RESULTS IN THE FORMATION OF MANNOSE-6-PHOSPHATE.
THE PEP-DEPENDENT SUGAR TRANSPORTING PHOSPHOTRANSFERASE SYSTEM TRANSPORTS AND SIMULTANEOUSLY PHOSPHORYLATES ITS SUGAR SUBSTRATES. MANNOSE XYZ PERMEASE IS A MEMBER OF THE FAMILY, WITH THIS DISTINCT METHOD BEING USED BY BACTERIA FOR SUGAR UPTAKE PARTICULARLY EXOGENOUS HEXOSES IN THE CASE OF MANNOSE XYZ TO RELEASE THE PHOSPHATE ESTERS INTO THE CELL CYTOPLASM IN PREPARATION FOR METABOLISM PRIMARILY THROUGH THE ROUTE OF GLYCOLYSIS.[9] THE MANXYZ TRANSPORTER COMPLEX IS ALSO INVOLVED IN INFECTION OF E. COLI BY BACTERIOPHAGE LAMBDA, WITH SUBUNIT MANY AND MANZ BEING SUFFICIENT FOR PROPER LAMBDA PHAGE INFECTION.[10] MANXYZ POSSESSES FOUR DOMAINS IN THREE POLYPEPTIDE CHAINS; MANX, MANY, AND MANZ. THE MANX SUBUNIT FORMS A HOMODIMER THAT IS LOCALIZED TO THE CYTOPLASMIC SIDE OF THE MEMBRANE. MANX CONTAINS TWO DOMAINS IIA AND IIB LINKED BY A HINGE PEPTIDE WITH EACH DOMAIN CONTAINING A PHOSPHORYLATION SITE AND PHOSPHORYL TRANSFER OCCURS BETWEEN BOTH SUBUNITS.[11] MANX CAN BE MEMBRANE BOUND OR NOT.[10] THE MANY AND MANNZ SUBUNITS ARE HYDROPHOBIC INTEGRAL MEMBRANE PROTEINS WITH SIX AND ONE TRANSMEMBRANE ALPHA HELICAL SPANNER(S).[12] [13] THE PHOSPHORYL GROUP OF PEP IS TRANSFERRED TO THE IMPORTED SUGAR VIA ENZYME 1, HISTIDINE PROTEIN PHOSPHATE CARRIER, AND THEN TO THE MANX, MANY, AND MANZ SUBUNITS OF THE MANXYZ TRANSPORTATION COMPLEX, WHICH PHOSPHORYLATES THE ENTERING HEXOSE SUGAR, CREATING A HEXOSE-6-PHOSPHATE.
D-MANNOSE IS A KIND OF SUGAR THAT IS RELATED TO GLUCOSE .
D-MANNOSE IS USED FOR PREVENTING URINARY TRACT INFECTIONS (UTIS ) AND TREATING CARBOHYDRATE -DEFICIENT GLYCOPROTEIN SYNDROME, AN INHERITED METABOLIC DISORDER .
HOW DOES IT WORK?
D-MANNOSE MIGHT TREAT THE DEFICIENCY CAUSED BY A GENETIC DEFECT THAT CAUSES ABNORMAL BREAKDOWN AND PRODUCTION OF MANNOSE. D-MANNOSE MIGHT PREVENT CERTAIN KINDS OF BACTERIA FROM STICKING TO THE WALLS OF THE URINARY TRACT AND CAUSING INFECTION.
USES & EFFECTIVENESS
POSSIBLY EFFECTIVE FOR
Β· TREATING A RARE INHERITED DISORDER CALLED CARBOHYDRATE-DEFICIENT GLYCOPROTEIN SYNDROME TYPE 1B. TAKING D-MANNOSE SEEMS TO IMPROVE PROTEIN LOSS, LIVER FUNCTION, LOW BLOOD SUGAR, AND BLOOD CLOTTING DISORDERS IN PEOPLE WITH THIS CONDITION.
INSUFFICIENT EVIDENCE FOR
Β· PREVENTING AND TREATING URINARY TRACT INFECTIONS (UTIS). EARLY RESEARCH SHOWS THAT TAKING D-MANNOSE FOR 13 DAYS MIGHT REDUCE SYMPTOMS OF UTIS, SUCH AS BURNING AND INCREASED URINATION. ALSO, TAKING D-MANNOSE POWDER FOR 6 MONTHS AFTER A UTI MIGHT PREVENT UTIS FROM OCCURRING AGAIN.
Β· OTHER CONDITIONS.
MORE EVIDENCE IS NEEDED TO RATE THE EFFECTIVENESS OF D-MANNOSE FOR THESE USES.
SIDE EFFECTS & SAFETY
D-MANNOSE IS POSSIBLY SAFE FOR MOST ADULTS WHEN TAKEN BY MOUTH . IT CAN CAUSE DIARRHEA , LOOSE STOOLS, AND BLOATING . IN HIGH DOSES, IT MIGHT HARM THE KIDNEYS .
SPECIAL PRECAUTIONS & WARNINGS:
PREGNANCY AND BREAST -FEEDING: NOT ENOUGH IS KNOWN ABOUT THE USE OF D-MANNOSE DURING PREGNANCY AND BREAST-FEEDING. STAY ON THE SAFE SIDE AND AVOID USE.
DIABETES : SOME RESEARCH SUGGESTS THAT D-MANNOSE MIGHT MAKE BLOOD SUGAR CONTROL MORE DIFFICULT IN PEOPLE WITH DIABETES.
INTERACTIONS
WE CURRENTLY HAVE NO INFORMATION FOR D-MANNOSE INTERACTIONS.
DOSING
THE FOLLOWING DOSES HAVE BEEN STUDIED IN SCIENTIFIC RESEARCH:
CHILDREN
BY MOUTH :
Β· FOR TREATING A RARE INHERITED DISORDER CALLED CARBOHYDRATE-DEFICIENT GLYCOPROTEIN SYNDROME TYPE 1B: 0.3-1 GRAMS/KG OF D-MANNOSE DAILY HAS BEEN USED.