Mannose and glucose, although having the same molecular formula (C ? H ?? O ?), are both aldoses and are C-2 isomers (i.e. the direction of the hydroxyl group on the second carbon atom is different), but their metabolic pathways and physiological functions differ significantly. The following provides a detailed comparison of their metabolic differences from multiple perspectives:

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1. Intestinal absorption

Glucose:

Efficient absorption: It is mainly actively transported by SGLT1 (sodium glucose cotransporter 1) in small intestinal epithelial cells. The absorption rate is extremely high (>95%), which can quickly enter the bloodstream and raise blood sugar.

Dependent on sodium ion gradient. ?

Mannose:

Inefficient absorption: mainly through facilitated diffusion (possibly involving GLUT family transporters such as GLUT5 or similar channels). The absorption rate is very low (about 10-20%), and most of the unabsorbed mannose enters the colon and is fermented by intestinal bacteria or excreted with feces.

2. Enter the bloodstream

Glucose:

After absorption, it directly enters the portal vein circulation, causing a rapid increase in blood sugar levels.

Mannose:

The absorption amount is low, and the concentration of mannose in the blood is extremely low (normal fasting plasma concentration is about 50 μ mol/L, much lower than 4-6 mmol/L of glucose). Oral administration of mannose does not cause significant fluctuations in blood sugar levels.

3. Initial steps of tissue uptake and metabolism

Glucose:

Insulin dependent: Muscle and adipose tissue uptake of glucose is highly dependent on insulin signaling (via GLUT4 transporter).

Hexokinase/Glucokinase: After entering cells, it is phosphorylated by hexokinase (HK) (systemic tissue) or glucokinase (GK) (liver) to glucose-6-phosphate (G6P). This is the core hub molecule of sugar metabolism.

Mannose:

Not dependent on insulin: Tissue uptake is not dependent on insulin.

Mannokinase (MK): It is mainly phosphorylated by mannokinase in the liver (with a small amount in other tissues such as the kidneys) to mannose-6-phosphate (Man-6-P). This is a key rate limiting step in mannose metabolism.

Phosphomannose isomerase (PMI): Man-6-P is converted to fructose-6-phosphate (F6P) by phosphomannose isomerase. F6P is an intermediate product of the glycolysis pathway.

4. Main metabolic pathways

Glucose:

Glycolysis energy supply: G6P can enter the glycolysis pathway to produce energy (ATP).

Glycogen synthesis: The synthesis and storage of glycogen in the liver and muscles.

The pentose phosphate pathway: generates NADPH and ribose-5-phosphate (used for reducing biosynthesis and nucleotide synthesis).

Fat synthesis: When excess is present, it is converted into fat.

Mannose:

Conversion into glycolytic intermediates: After PMI conversion to F6P, it can enter the glycolytic pathway (the final portion can be converted into glucose or completely oxidized for energy supply).

Glycosylation precursor: Its main function is to serve as the starting sugar group for synthesizing N-linked sugar chains! Man-6-P can be further converted into GDP mannose in vivo, serving as a direct donor of mannose residues in glycoproteins and glycolipids.

Glycosylation: Mannose is a key component of the core oligosaccharide chain in protein N-linked glycosylation modification (such as Man ? GlcNAc ?). This process occurs in the endoplasmic reticulum and Golgi apparatus, and is crucial for protein folding, stability, localization, and function (such as antibodies, hormone receptors, and cell adhesion molecules).

Conversion to glucose/glycogen: The efficiency is low, and some F6P reversible glycolysis pathways generate G6P, which is then converted to glucose or glycogen, but the contribution is small.

5. Effects on blood glucose and insulin

Glucose:

Significantly elevated blood sugar: is the main source of blood sugar.

Intense stimulation of insulin secretion: Pancreatic beta cells directly sense an increase in blood sugar and secrete insulin.

Mannose:

Almost does not affect blood sugar: absorbs less, metabolizes without producing glucose, and does not rely on insulin.

Not stimulating insulin secretion: lacking effective blood glucose stimulation signals.

6. Core differences in physiological functions

Glucose:

Core function: The main source of rapid energy (especially the brain, muscles, and red blood cells), maintaining blood sugar homeostasis.

Mannose:

Core function: A key precursor substance for glycosylation biosynthesis, supporting the structure and function of glycoproteins and glycolipids (cell recognition, signal transduction, immunity, protein folding, etc.).

Secondary function: Prevent urinary tract infections (by blocking bacterial adhesion).

7. Clinical application differences

Glucose:

Energy supplementation (infusion), hypoglycemic treatment, glucose tolerance test.

Mannose:

Prevention of recurrent urinary tract infections (mainly targeting Escherichia coli) and treatment of specific rare genetic glycosylation disorders (such as CDG Ib MPI deficiency).