Pathways

Sevoflurane is an inhalation anaesthetic agent used for induction and maintenance of general anesthesia during surgical procedures. It can be found under the brand names Sevorane, Sojourn, and Ultane. It is a volatile, non-flammable compound with a low solubility profile and blood/gas partition coefficient. Sevoflurane was patented in 1972, was approved for clinical use in Japan in 1990, and approved by the FDA in 1996. Sevoflurane is three times more potent than desflurane, but has lower potency compared to halothane and isoflurane. Unlike other volatile anesthetics, sevoflurane has a pleasant odor and does not irritate the airway. The hemodynamic and respiratory depressive effects of sevoflurane are well tolerated, and most patients receiving this anesthetic agent present little toxicity. Therefore, it can be used for inhalational induction in adults and children for a wide variety of anesthetic procedures. The precise mechanism of action of sevoflurane has not been fully elucidated. Like other halogenated inhalational anesthetics, sevoflurane induces anesthesia by binding to ligand-gated ion channels and blocking CNS neurotransmission. It has been suggested that inhaled anesthetics enhance inhibitory postsynaptic channel activity by binding GABAA receptors. This ability to modulate ion channel activity can also regulate cardiac excitability and contractility. Sevoflurane acts as a positive allosteric modulator of the GABAA receptor in electrophysiology studies of neurons and recombinant receptors. Some side effects of using sevoflurane may include blurred vision, chest pain, choking, and dizziness. Sevoflurane is expected to exert its action via a majority of mechanisms, including GABA(A) agonism, glycine agonism, glutamate antagonism, inhibiting calcium transporting ATPases, and activating potassium channels. It is administered via respiratory inhalation.

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The shikimate pathway is composed of seven enzymatic reactions in the chloroplast by which phosphoenolpyruvate (PEP) and D-erythrose 4-phosphate (E4P) are converted to chorismate, the common precursor of the aromatic amino acids phenylalanine, tyrosine, and tryptophan as well as other metabolites (e.g. folates). The pathway's absence in animals makes it an attractive target for new antimicrobial agents, anti-parasitic agents, and herbicides. PEP can enter this pathway either from plastidic glycolysis or cytosolic glycolysis. If it enters from the cytosol, then it is pumped into the chloroplast by PEP/phosphate translocator (PPT), an antiporter that exports phosphate into the cytosol simultaneously. Firstly, DAHP synthase, with the help of reduced thioredoxin (TRX) and a divalent cation (e.g. manganese) as cofactors, converts PEP, E4P, and water to 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP) and phosphate. Secondly, 3-dehydroquinate synthase eliminates a phosphate from DAHP resulting in 3-dehydroquinate. This enzyme requires NAD+ and a divalent cation (e.g. cobalt) as cofactors. The next two reactions are catalyzed by the bifunctional enzyme 3-dehydroquinate dehydratase-shikimate dehydrogenase (DHQ-SDH). In the pathway's third reaction, the enzyme's DHQ domain dehydrates 3-dehydroquinate to 3-dehydroshikimate. In the fourth reaction, the enzyme's SDH domain uses NADPH to reversibly reduce 3-dehydroshikimate to shikimate, releasing NADP in the process. Fifthly, shikimate kinase, which requires a divalent cation (e.g. manganese) as a cofactor, catalyzes the ATP-dependent phosphorylation of shikimate to shikimate 3-phosphate. Sixthly, 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase converts shikimate-3-phosphate and PEP to EPSP, releasing a phosphate in the process. Seventhly, chorismate synthase (CS) catalyzes the 1,4-trans elimination of the phosphate group from EPSP to form chorismate. This enzyme requires reduced flavin mononucleotide (FMNH2) as a cofactor.

3-hydroxyacyl-CoA dehydrogenase deficiency, also known as HADH deficiency or formerly SCHAD deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the mitochondrial beta-oxidation of short chain saturated fatty acid pathway. It is caused by a mutation in the HADH gene which encodes the mitochondrial enzyme hydroxyacyl-coenzyme A dehydrogenase. This enzyme is responsible for the beta-oxidation of 3-hydroxyhexanoyl-CoA and 3-hydroxybutyryl-CoA into 3-oxohexanoyl-CoA and acetoacetyl-CoA respectively. Symptoms of HADH deficiency include hypoglycemia, as well as vomiting, diarrhea and seizures. Treatment with diazoxide, a potassium channel activator, has been effective. It is estimated that HADH deficiency affects less than 1 in 1,000,000 individuals.

3-hydroxyacyl-CoA dehydrogenase deficiency, also known as HADH deficiency or formerly SCHAD deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the mitochondrial beta-oxidation of short chain saturated fatty acid pathway. It is caused by a mutation in the HADH gene which encodes the mitochondrial enzyme hydroxyacyl-coenzyme A dehydrogenase. This enzyme is responsible for the beta-oxidation of 3-hydroxyhexanoyl-CoA and 3-hydroxybutyryl-CoA into 3-oxohexanoyl-CoA and acetoacetyl-CoA respectively. Symptoms of HADH deficiency include hypoglycemia, as well as vomiting, diarrhea and seizures. Treatment with diazoxide, a potassium channel activator, has been effective. It is estimated that HADH deficiency affects less than 1 in 1,000,000 individuals.