Hemicholinium-3 (HC3), also known as hemicholine, is a

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...

which blocks the reuptake of choline by the high-affinity

choline transporter The high-affinity choline transporter (ChT) also known as solute carrier family 5 member 7 is a protein in humans that is encoded by the ''SLC5A7'' gene. It is a cell membrane transporter and carries choline into acetylcholine-synthesizing neuro ...

(ChT; encoded in humans by the gene ''SLC5A7'') at the presynapse. The reuptake of choline is the rate-limiting step in the synthesis of

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...

; hence, hemicholinium-3 decreases the synthesis of acetylcholine. It is therefore classified as an indirect

acetylcholine antagonist Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous sy ...

. Acetylcholine is synthesized from choline and a donated

acetyl In organic chemistry, acetyl is a functional group with the chemical formula and the structure . It is sometimes represented by the symbol Ac (not to be confused with the element actinium). In IUPAC nomenclature, acetyl is called ethanoyl, ...

group from

acetyl-CoA Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for ...

, by the action of

choline acetyltransferase Choline acetyltransferase (commonly abbreviated as ChAT, but sometimes CAT) is a transferase enzyme responsible for the synthesis of the neurotransmitter acetylcholine. ChAT catalyzes the transfer of an acetyl group from the coenzyme acetyl-Co ...

(ChAT). Thus, decreasing the amount of choline available to a neuron will decrease the amount of acetylcholine produced. Neurons affected by hemicholinium-3 must rely on the transport of choline from the soma (cell body), rather than relying on reuptake of choline from the synaptic cleft.

Toxicity

Hemicholinium-3 is highly toxic because it interferes with cholinergic neurotransmission. The LD50 of hemicholinium-3 for mice is about 35 μg.

References

{{Acetylcholine metabolism and transport modulators Lactols Phenylmorpholines Quaternary ammonium compounds Acetylcholine synthesis inhibitors Biphenyls

Toxicity

See also

References