Pathways

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.

Neostigmine is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Neostigmine passes through the liver and is then excreted from the body mainly through the kidney.

Nepafenac (also named nevanac or ilevro or amfenac amide) is a nonsteroidal anti-inflammatory drug (NSAID). It can be used to treat pain and inflammation that is associated with cataract surgery. Nepafenac can block prostaglandin synthesis by the action of inhibition of prostaglandin G/H synthase 1 and 2. Prostaglandin G/H synthase 1 and 2 catalyze the arachidonic acid to prostaglandin G2, and also catalyze prostaglandin G2 to prostaglandin H2 in the metabolism pathway. Decreased prostaglandin synthesis in many animal model's cell is caused by presence of nepafenac.

Nepafenac is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Nepafenac passes through the liver and is then excreted from the body mainly through the kidney.

Nepafenac is an ophthalmic non-steroidal anti-inflammatory prodrug (NSAID) used for the treatment of pain and inflammation associated with cataract surgery. It targets the prostaglandin G/H synthase-1 (COX-1) and prostaglandin G/H synthase-2 (COX-2) in the cyclooxygenase pathway. The cyclooxygenase pathway begins in the cytosol with phospholipids being converted into arachidonic acid by the action of phospholipase A2. The rest of the pathway occurs on the endoplasmic reticulum membrane, where prostaglandin G/H synthase 1 & 2 convert arachidonic acid into prostaglandin H2. Prostaglandin H2 can either be converted into thromboxane A2 via thromboxane A synthase, prostacyclin/prostaglandin I2 via prostacyclin synthase, or prostaglandin E2 via prostaglandin E synthase. COX-2 is an inducible enzyme, and during inflammation, it is responsible for prostaglandin synthesis. It leads to the formation of prostaglandin E2 which is responsible for contributing to the inflammatory response by activating immune cells and for increasing pain sensation by acting on pain fibers. Nepafenac inhibits the action of COX-1 and COX-2 on the endoplasmic reticulum membrane. This reduces the formation of prostaglandin H2 and therefore, prostaglandin E2 (PGE2). The low concentration of prostaglandin E2 attenuates the effect it has on stimulating immune cells and pain fibers, consequently reducing inflammation and pain. This drug is administered as an ophthalmic drop or suspension.