Neuroscience: Neurotransmitters (small molecule and neuroactive), storage release removal and disease. 1.
The brain is made up of neurons that process and transmit information by electrochemical signaling. Neurotransmitters are endogenous chemicals which relay, amplify, and modulate signals between a neuron and another cell. Chemical messengers must fulfill four criteria to be considered a transmitter. These four steps include the synthesis of a transmitter substance, the storage and release of the substance, its interaction with a receptor in the membrane, and the removal of the transmitter form the synaptic cleft. The nervous system makes use of two types of neurotransmitters: small-molecule transmitters (acetylcholine, amines and A.A) and neuroactive transmitters(peptides)
Neurons have developed a sophisticated ability to regulate the synthesis, storage, release, and degradation (or removal) of neurotransmitters to achieve the desired levels of transmitter molecules. In general, each of these processes is specific to the transmitter involved, requiring enzymes found only in neurons that use the transmitter at their synapses. The synthesis of small-molecule neurotransmitters occurs within presynaptic terminals. The enzymes needed for transmitter synthesis are synthesized in the neuronal cell body and transported to the nerve terminal cytoplasm by a mechanism called slow axonal transport. The enzymes generate a cytoplasmic pool of neurotransmitter that must then be loaded into synaptic vesicles by transport proteins in the vesicular membrane. The mechanisms responsible for the synthesis and storage of peptide transmitters are fundamentally different from those used for the smallmolecule neurotransmitters. Peptide-secreting neurons generally synthesize polypeptides in their cell bodies that are quite large. Processing these polypeptides, which are called pre-propeptides takes place by a sequence of reactions in several intracellular organelles. Pre-propeptides are synthesized in the rough endoplasmic reticulum, where the signal sequence of amino acids—that is, the sequence indicating that the peptide is to be secreted—is removed. The remaining polypeptide, called a propeptide then traverses the Golgi apparatus and is stored into vesicles in the trans-Golgi network. The final stages of peptide neurotransmitter processing occur after packaging into vesicles. The peptide-filled vesicles must therefore be transported along the axon to the synaptic terminal. The mechanism responsible for such movement, known as fast axonal transport, carries vesicles along cytoskeletal elements called microtubules. The release of a neurotransmitter is triggered by the arrival of a nerve impulse and occurs through an unusually rapid process of cellular secretion, also known as exocytosis: Within the presynaptic nerve terminal, vesicles containing neurotransmitter sit "docked" and ready at the synaptic membrane. The arriving action potential produces an influx of calcium ions through voltage-dependent, calcium-selective ion channels at the down stroke of the action potential. Calcium ions then trigger a biochemical cascade which results in vesicles fusing with the presynaptic membrane and releasing their contents to the synaptic cleft. Vesicle fusion is driven by the action of a set of proteins in the presynaptic terminal known as SNAREs. As calcium ions enter into the presynaptic neuron, they bind with the proteins found within the membranes of the synaptic vesicles that allow the vesicles to "dock." Triggered by the binding of the calcium ions, the synaptic vesicle proteins begin to move apart, resulting in the creation of a fusion pore. The presence of the pore allows for the release of neurotransmitter into the synapse. The membrane added by this fusion is later retrieved by endocytosis and recycled for the formation of fresh neurotransmitter-filled vesicles. After a neurotransmitter molecule binds to a receptor molecule, it does not...
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