Pathways

Acetylcysteine is a medication that can be used as a mucolytic in patients with certain lung conditions and as an antidote for acetaminophen overdose. A number of possible mechanisms for the mucolytic activity of acetylcysteine have been proposed. Acetylcysteine's sulfhydryl groups may hydrolize disulfide bonds within mucin, breaking down the oligomers, and making the mucin less viscous Acetaminophen (APAP) is metabolized in 3 main ways: glucuronidation, sulfation and oxidation. Glucuronidation and sulfation of acetaminophen produces non-toxic acetaminophen conjugates (APAP-glucuronide and APAP-sulfate). In the case of acetaminophen overdoses, a portion of the drug is metabolized by CYP2E1 to form the potentially toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). The amount of NAPQI produced in an overdose saturates and depletes glutathione stores. Acetylcysteine can directly conjugate NAPQI or provide cysteine for glutathione production and NAPQI conjugation. Acetylcysteine can also provide sulfur for the sulfate conjugation of acetaminophen. Therefore, acetylcysteine aims to prevent formation of toxic NAPQI and detoxify NAPQI that has already been formed. NAPQI can cause mitochondrial dysfunction and leading to necrotic cell death. Acetylcysteine may prevent cellular toxicity by increasing oxygen delivery to tissues, increasing mitochondrial ATP production, and altering the microvascular tone to increase the blood flow and oxygen delivery to the liver and other vital organs. Oral NAC may cause nausea, vomiting, diarrhea, flatus, and gastroesophageal reflux. IV NAC can cause rate related anaphylactoid reactions in up to 18% of patients, which is not an issue with the oral route. Most of the anaphylactoid reactions are mild (6%) or moderate (10%) with severe reactions like bronchospasm and hypotension rare at 1%.

NF-kB transcription factor plays a role in the inflammatory and immune response of mammals. Acetylation of RelA regulates NF-kB activity. Tumor necrosis factor activates tumor necrosis factor receptor, recruiting proteins FADD, TRADD, RIP and TRAF6 to activate the NF-kB pathway. Activation of IKK complex causes the phosphorylation of I-kappa-B-alpha and triggers its degradation. I-kappa-B-alpha normally sequesters KF-kB in the cytoplasm, following its degradation, RELA and p50 (subunits of NF-kB) are liberated can translocate to the nucleus to activate gene expression. RelA and p50 associate with p300 and CREB transcriptional co-activators causing the acetylation of RelA and increase in transcriptional activity. Acetylated RelaA is targeted for deacetylation by transcriptional co-repressor Histone deacetylation 3 (HDAC3). This promotes its binding to I-kappa-B-alpha causing NF-kB's transport out of the nucleus and reduces its activity.

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

Acetyl sulfisoxazole is an antibacterial from the sulfanilamide drug class. It is a broad-spectrum antibiotic indicated against urinary tract infections, meningococcal meningitis, acute otitis media, inclusion conjunctivitis, toxoplasmosis, and many others. Acetyl sulfisoxazole is a synthetic bacteriostatic, meaning that it stops the bacteria from growing. This drug binds competitively to the dihydropteroate synthase enzyme. This enzyme is essential to produce dihydrofolic acid in bacteria, when it is inhibited, the bacteria cannot grow anymore because they cannot produce DNA with the folic acid. Thus drug is administered as an oral tablet. N1-acetyl sulfisoxazole is metabolized to sulfisoxazole by digestive enzymes in the gastrointestinal tract and is absorbed as sulfisoxazole (the active compound).

metabolic pathway of acetyl CoA production by PDH and Krebs cycle