Galactosamine is a hexosamine derived from galactose with the molecular formula C₆H₁₃NO₅. This

amino sugar In organic chemistry, an amino sugar (or more technically a 2-amino-2-deoxysugar) is a sugar molecule in which a hydroxyl group has been replaced with an amine group. More than 60 amino sugars are known, with one of the most abundant being ''N''- ...

is a constituent of some

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glyco ...

hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...

s such as

follicle-stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, ...

(FSH) and

luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) ...

(LH). Precursors such as

uridine diphosphate Uridine diphosphate, abbreviated UDP, is a nucleotide diphosphate. It is an ester of pyrophosphoric acid with the nucleoside uridine. UDP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase uracil. UDP is an im ...

(UDP), UDP-''N''-acetyl-D-glucosamine, or

glucosamine Glucosamine (C6H13NO5) is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Glucosamine is part of the structure of two polysaccharides, chitosan and chitin. Glucosamine is one of the most ...

are used to synthesize galactosamine in the human body. A derivative of this compound is ''N''-acetyl-D-galactosamine. Galactosamine is a

hepatotoxic Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn fr ...

, or liver-damaging, agent that is sometimes used in animal models of liver failure.

Hepatotoxicity

Galactosamine is used to induce hepatitis in rodent liver for research purposes. The result of using galactosamine to induce hepatitis is a disease model in which there is

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated diges ...

and inflammation of the liver. This type of tissue damage triggered by galactosamine resembles drug-induced liver disease in humans.

Mechanism of hepatotoxicity

The proposed mechanism behind galactosamine-induced hepatitis is depletion of the energy source of

hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, ...

s. In the Leloir pathway galactosamine is metabolized into galactosamine-1-phosphate (by

galactokinase Galactokinase is an enzyme (phosphotransferase) that facilitates the phosphorylation of α-D-galactose to galactose 1-phosphate at the expense of one molecule of ATP. Galactokinase catalyzes the second step of the Leloir pathway, a metabolic p ...

) and UDP-galactosamine (by UDP-galactose uridyltransferase). It is hypothesized that this leads to UDP-galactosamine accumulation within cells, and

uridine triphosphate Uridine-5′-triphosphate (UTP) is a pyrimidine nucleoside triphosphate, consisting of the organic base uracil linked to the 1′ carbon of the ribose sugar, and esterified with tri- phosphoric acid at the 5′ position. Its main role is as sub ...

(UTP), UDP, and

uridine monophosphate Uridine monophosphate (UMP), also known as 5′-uridylic acid (conjugate base uridylate), is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid with the nucleoside uridine. UMP consists of the phosphate group, th ...

(UMP) decrease. The depletion of high-energy molecules such as UTP leads to a disruption in hepatocyte metabolism. Additionally, other derivatives of uridine such as UDP-glucose are depleted and this interferes with glycogen synthesis in the cell. Another recent hypothesis states that overexpression of pro-inflammatory cytokines (such as NFκB-dependent_ NFκB-dependent_inducible_nitric_oxide_synthase">NF-κB.html"_;"title="tumor_necrosis_factor_(TNFα)_and_NF-κB">NFκB-dependent_inducible_nitric_oxide_synthase_(iNOS)_over_expression_play_a_role_in_galactosamine-induced_damage_to_liver_cells.

_See_also

*_N-Acetylgalactosamine.html" ;"title="inducible_nitric_oxide_synthase.html" ;"title="NF-κB.html" ;"title="tumor necrosis factor (TNFα) and NF-κB">NFκB-dependent inducible nitric oxide synthase">NF-κB.html" ;"title="tumor necrosis factor (TNFα) and NF-κB">NFκB-dependent inducible nitric oxide synthase (iNOS) over expression play a role in galactosamine-induced damage to liver cells.

References

External links

* {{MeshName, Galactosamine Hexosamines

Hepatotoxicity

Mechanism of hepatotoxicity

_See_also

See also

References

External links