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The drug, a macrolide (polyhydroxylated lactone), is a member of a structural diverse class of compounds called polyketides with notable chemical mechanism of action. It stabilizes the microtubules of target cells, essentially arresting them at a specific stage in the cell cycle and halting cell division.
Microtubule and tubulin metrics [1]. Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm [2] and have an inner diameter between 11 and 15 nm. [3]
Colchicine has a narrow therapeutic index, so overdosing is a significant risk. Common side effects of colchicine include gastrointestinal upset, particularly at high doses. [14] Severe side effects may include pancytopenia (low blood cell counts) and rhabdomyolysis (damage to skeletal muscle), and the medication can be deadly in overdose. [11]
The cytoskeleton consists of (a) microtubules, (b) microfilaments, and (c) intermediate filaments. [1]The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. [2]
It binds colchicine much more slowly than other isotypes of β-tubulin. [29] β1-tubulin, sometimes called class VI β-tubulin, [30] is the most divergent at the amino acid sequence level. [31] It is expressed exclusively in megakaryocytes and platelets in humans and appears to play an important role in the formation of platelets. [31]
Microtubules function as tracks in the intracellular transport of membrane-bound vesicles and organelles. This process is propelled by motor proteins such as dynein . Motor proteins connect the transport vesicles to microtubules and actin filaments to facilitate intracellular movement. [ 1 ]
Animal cells (and some filamentous fungi are thought to rely upon the microtubule cytoskeleton and associated motor proteins. [citation needed] Although plants, algae and fungi transport depends on myosins, which move along the actin cytoskeleton, certain organelles can move along microtubules in plant cells. [3]
The microtubule-organizing center (MTOC) is a structure found in eukaryotic cells from which microtubules emerge. MTOCs have two main functions: the organization of eukaryotic flagella and cilia and the organization of the mitotic and meiotic spindle apparatus, which separate the chromosomes during cell division.