GM1
Encyclopedia
GM1 the "prototype" ganglioside
, is a member of the ganglio series of gangliosides which contain one sialic acid
residue. GM1 has important physiological properties and impacts neuronal plasticity
and repair mechanisms, and the release of neurotrophins in the brain
. Besides its function in the physiology of the brain, GM1 acts as the site of binding for both Cholera toxin
and E. coli
heat-labile enterotoxin
(Traveller's diarrhea).
Antibodies to GM1
are increased in Guillain-Barré syndrome
, dementia
and lupus
but their function is not clear. There is some evidence to suggest these antibodies are associated with diarrhea
in Guillain-Barré syndrome
.
produces a multimeric toxin called the cholera toxin
. The A1 subunit of this toxin will gain entry to intestinal epithelial cells with the assistance of the B subunit via the GM1 ganglioside receptor. Once inside, the A1 subunit will ADP ribosylate the Gs
Alpha subunit which will prevent its GTPase
activity. This will lock it in the active state and it will continuously stimulate adenylate cyclase. The sustained adenylate cyclase activity will lead to a sustained increase of cAMP
which will cause electrolyte and water loss, causing diarrhea
.
Fortunately, the SGLT1 receptor is present in the small intestine. When the cholera patient is given a solution containing water, sodium
and glucose
, the SGLT1 receptor will reabsorb sodium and glucose, while water will be passively absorbed with the sodium. This will replace the water and electrolyte
loss in the cholera induced diarrhea.
Ganglioside
Ganglioside is a molecule composed of a glycosphingolipid with one or more sialic acids linked on the sugar chain. The 60+ known gangliosides differ mainly in the position and number of NANA residues.It is a component of the cell plasma membrane that modulates cell signal transduction events...
, is a member of the ganglio series of gangliosides which contain one sialic acid
Sialic acid
Sialic acid is a generic term for the N- or O-substituted derivatives of neuraminic acid, a monosaccharide with a nine-carbon backbone. It is also the name for the most common member of this group, N-acetylneuraminic acid...
residue. GM1 has important physiological properties and impacts neuronal plasticity
Neuroplasticity
Neuroplasticity is a non-specific neuroscience term referring to the ability of the brain and nervous system in all species to change structurally and functionally as a result of input from the environment. Plasticity occurs on a variety of levels, ranging from cellular changes involved in...
and repair mechanisms, and the release of neurotrophins in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
. Besides its function in the physiology of the brain, GM1 acts as the site of binding for both Cholera toxin
Cholera toxin
Cholera toxin is a protein complex secreted by the bacterium Vibrio cholerae. CTX is responsible for the massive, watery diarrhea characteristic of cholera infection.- Structure :...
and E. coli
Enterotoxigenic Escherichia coli
Enterotoxigenic Escherichia coli is a type of Escherichia coli and the leading bacterial cause of diarrhea in the developing world, as well as the most common cause of traveler's diarrhea. Each year, approximately 210 million cases and 380,000 deaths occur, mostly in children, from ETEC...
heat-labile enterotoxin
Heat-labile enterotoxin
Heat-labile enterotoxin is a type of labile toxin found in Escherichia coli that is inactivated at high temperatures.It acts similarly to the cholera toxin by raising cAMP levels through ADP-ribosylation of the alpha-subunit of a Gs protein leading to the constitutive activation of adenylate cyclase...
(Traveller's diarrhea).
Antibodies to GM1
Anti-ganglioside antibodies
Anti-ganglioside antibodies that react to self-gangliosides are found in autoimmune neuropathies. These antibodies were first found to react with cerebellar cells...
are increased in Guillain-Barré syndrome
Guillain-Barré syndrome
Guillain–Barré syndrome , sometimes called Landry's paralysis, is an acute inflammatory demyelinating polyneuropathy , a disorder affecting the peripheral nervous system. Ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk, is the most typical symptom...
, dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
and lupus
Lupus erythematosus
Lupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...
but their function is not clear. There is some evidence to suggest these antibodies are associated with diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
in Guillain-Barré syndrome
Guillain-Barré syndrome
Guillain–Barré syndrome , sometimes called Landry's paralysis, is an acute inflammatory demyelinating polyneuropathy , a disorder affecting the peripheral nervous system. Ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk, is the most typical symptom...
.
GM1 and the cholera toxin
The bacteria Vibrio choleraeVibrio cholerae
Vibrio cholerae is a Gram-negative, comma-shaped bacterium. Some strains of V. cholerae cause the disease cholera. V. cholerae is facultatively anaerobic and has a flagella at one cell pole. V...
produces a multimeric toxin called the cholera toxin
Cholera toxin
Cholera toxin is a protein complex secreted by the bacterium Vibrio cholerae. CTX is responsible for the massive, watery diarrhea characteristic of cholera infection.- Structure :...
. The A1 subunit of this toxin will gain entry to intestinal epithelial cells with the assistance of the B subunit via the GM1 ganglioside receptor. Once inside, the A1 subunit will ADP ribosylate the Gs
GS
-Places:* South Georgia and the South Sandwich Islands ** .gs, an Internet country code top-level domain-Science:* g-force , multiples of the acceleration due to gravity* Guanosine synthetase-Technologies:* Glideslope* Ground Speed...
Alpha subunit which will prevent its GTPase
GTPase
GTPases are a large family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate . The GTP binding and hydrolysis takes place in the highly conserved G domain common to all GTPases.-Functions:...
activity. This will lock it in the active state and it will continuously stimulate adenylate cyclase. The sustained adenylate cyclase activity will lead to a sustained increase of cAMP
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
which will cause electrolyte and water loss, causing diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
.
Fortunately, the SGLT1 receptor is present in the small intestine. When the cholera patient is given a solution containing water, sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
and glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
, the SGLT1 receptor will reabsorb sodium and glucose, while water will be passively absorbed with the sodium. This will replace the water and electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....
loss in the cholera induced diarrhea.