Pathways

Neomycin is a member of the aminoglycoside family of antibiotics. As an aminoglycoside, neomycin can effectively against a wide variety of pathogenic bacteria such as E.coli, Citrobacter sp., etc. Neomycin can also effectively against Hemophilus influenzae, Salmonella sp. and others in vitro. However, netilmicin are ineffective against anaerobic bacteria, fungi and viruses. Neomycin binds irreversibly to the bacterial 30S ribosomal subunit protein and 16S rRNA and prevents the formation of the initiation complex with messenger RNA. More specifically, neomycin binds four nucleotides of the 16S rRNA and a single amino acid of protein S12. This interferes with the decoding site in the vicinity of nucleotide 1400 in 16S rRNA of the 30S subunit. This region interacts with the wobble base of the anticodon of tRNA. Binding of netilmicin can cause misreading of mRNA which result in insertion of incorrect amino acids to polypeptide. This lead to nonfunctional or toxic peptides of protein complex.

Neomycin is an antibiotic agent from the aminoglycoside family. It is administered as an oral tablet and as a topical ointment to treat bacterial infections. Neomycin is derived from Streptomyces fradiae by-products. There are three components A, B, and C, component B is the most active. This aminoglycoside is effective against gram-positive and gram-negative bacteria. It acts by binding to the 30S ribosomal subunit disrupting protein synthesis and inhibiting further translation. Specifically, this drug binds the 30S ribosomal protein S12. Due to its low absorption, overdosing is unlikely to occur, although a prolonged administration can cause the risk of neurotoxicity, ototoxicity, and nephrotoxicity in humans.

Neomycins are aminocyclitol antibiotics belonging to a broad spectrum of highly toxic antimicrobials and in this case, are shown to be produced by Streptomyces rubrolavendulae. Neomycin exists in two active forms of stereoisomers: neomycin B and neomycin C and a relatively inactive degenerate form in small quantities: neomycin A. Among many of its uses, neomycin was used to treat the illness tuberculosis but was deemed too toxic in its display of side effect.; it is now generally used to control infection during intestinal surgery. This pathway shows the biosynthesis of the active forms of neomycin: neomycin C and neomycin B from D-glucose. While the initial section of this pathway resembles the use of enzymes in similar pathways like the paromamine biosynthesis I and ribostamycin biosynthesis, the enzymes that are specific to the biosynthesis of neomycin are those involved in the five final steps of the pathway starting from ribostamycin. As shown in the pathway, these include UDP-GlcNAc: ribostamycin N-acetylglucosaminyltransferase, 2'-N-acetylparomamine deacetylase, paromamine 6'-oxidase, neamine transaminase NeoN, and radical SAM superfamily protein. It should be noted that the stereoisomer neomycin C is made first from which neomycin B is synthesized and this is an example of an epimerization reaction at C-5'' of neomycin C to B.

Neophaseic acid biosynthesis is a pathway that begins in the chloroplast and ends in the cytosol by which violaxanthin becomes neophaseate, synthesizing abscisic acid in the process. Neophaseate is an abscisic acid derivative whose synthesis provides a mechanism for controlling abscisic acid concentration. First, neoxanthin synthase catalyzes the opening of the violaxanthin epoxide ring to form neoxanthin. Second, a yet unidentified neoxanthin isomerase is theorized to isomerize neoxanthin to 9'-cis-neoxanthin. Third, 9-cis-epoxycarotenoid dioxygenase (NCED) uses oxygen to cleave 9'-cis-neoxanthin to form xanthoxin and C25-allenic-apo-aldehyde. This enzyme requires Fe2+ as a cofactor. Next, a xanthoxin transporter is theorized to export xanthoxin from the chloroplast into the cytosol to continue abscisic acid biosynthesis, but it has yet to be discovered. Fourth, xanthoxin dehydrogenase, located in the cytosol, catalyzes the conversion of xanthoxin and NAD to abscisic aldehyde, NADH, and a proton with the help of a molybdenum cofactor (MoCo). Fifth, abscisic-aldehyde oxidase converts abscisic aldehyde, water, and oxygen into hydrogen peroxide, hydrogen ion, and abscisic acid. Sixth, abscisic acid 8'-hydroxylase / abscisic acid 9'-hydroxylase uses NADPH, oxygen, and a proton to convert abscisic acid into 9'-hydroxyabscisate and water. Seventh, 9'-hydroxyabscisate spontaneously becomes neophaseate.

Neostigmine is a cholinesterase inhibitor used to treat myasthenia gravis and to try to combat muscle atrophy. By inhibiting the acetylcholinesterase enzyme, it can no longer breakdown acetylcholine allowing it to further interact with the nicotinic and muscarinic receptors.

Neostigmine is a cholinesterase inhibitor used in the symptomatic treatment of myasthenia gravis by improving muscle tone. Cholinergic neurons in the brain are primarily responsible for movement in skeletal muscles. In the neuron, acetylcholine is synthesized from acetyl-coa and choline, and stored into synaptic vesicles. When an action potential arrives at the nerve terminal, voltage-gated calcium channels open leading to an influx of calcium ions into the neuron. This triggers the docking of the synaptic vesicle and the release of acetylcholine into the synapse. Acetylcholine acts on nicotinic receptors on the motor end plate. Nicotinic receptors are cation channels, when activated they transport sodium ions into the motor end plate. The sodium causes depolarization of the cell, opening voltage-gated calcium channels on the sarcoplasmic reticulum. Calcium enters the cytosol from the sarcoplasmic reticulum and binds to calmodulin. Calmodulin activates myosin light chain kinase. Myosin light chain kinase converts myosin light chain to phosphorylated myosin light chain. The phosphorylated myosin light chain causes actin to become bound to myosin leading to muscle contraction. The acetylcholine in the synapse is cleared rapidly by acetylcholinesterase which breaks acetylcholine down into choline and acetate. Choline is taken back up into the presynaptic neuron and recycled to produce more acetylcholine. Neostigmine reversibly inhibits the acetylcholinesterase enzyme, which normally breaks down acetylcholine. The main pharmacological actions of this drug are believed to occur as the result of this enzyme inhibition, enhancing cholinergic transmission, which improves muscle tone. Common side effects include bradyarrhythmias, bronchospasm, miosis, nausea, and increased peristalsis.

Neostigmine is a cholinesterase inhibitor used in the symptomatic treatment of myasthenia gravis by improving muscle tone. Cholinergic neurons in the brain are primarily responsible for movement in skeletal muscles. In the neuron, acetylcholine is synthesized form acetyl-coa and choline, and stored into synaptic vesicles. When an action potential arrives at the nerve terminal, voltage gated calcium channels open leading to an influx of calcium ions into the neuron. This triggers the docking of the synaptic vesicle and release of acetylcholine into the synapse. Acetylcholine acts on nicotinic receptors on the motor end plate. Nicotinic receptors are cation channels, when activated they transport sodium ions into the motor end plate. The sodium causes depolarization of the cell, opening voltage gated calcium channels on the sarcoplasmic reticulum. Calcium enters the cytosol from the sarcoplasmic reticulum and binds to calmodulin. Calmodulin activates myosin light chain kinase. Myosin light chain kinase converts myosin light chain to phosphorylated myosin light chain. The phosphorylated myosin light chain causes actin to become bound to myosin leading to muscle contraction. The acetylcholine in the synapse is cleared rapidly by acetylcholinesterase which breaks acetylcholine down into choline and acetate. Choline is taken back up into the presynaptic neuron and recycled to produce more acetylcholine. Neostigmine reversibly inhibits the acetylcholinesterase enzyme, which normally breaks down acetylcholine. The main pharmacological actions of this drug are believed to occur as the result of this enzyme inhibition, enhancing cholinergic transmission, which improves muscle tone. Common side effects include bradyarrhythmias, bronchospasm, miosis, nausea, and increased peristalsis.