Pathways

Tropisetron is an indole derivative. Tropisetron competitively binds to and blocks the action of serotonin at 5HT3 receptors peripherally on vagus nerve terminals located in the gastrointestinal (GI) tract as well as centrally in the chemoreceptor trigger zone (CTZ) of the area postrema of the central nervous system (CNS). This results in the suppression of chemotherapy- and radiotherapy-induced nausea and vomiting.

Ipratropium is an anticholinergic drug used in the control of symptoms related to bronchospasm in chronic obstructive pulmonary disease (COPD). It can be found under the brand names Atrovent, Combivent, and Ipravent. It is commonly administered through inhalation which allows producing a local effect without presenting a significant systemic absorption. Ipratropium acts as an antagonist of the muscarinic acetylcholine receptor. This effect produces the inhibition of the parasympathetic nervous system in the airways and hence, inhibit their function. The function of the parasympathetic system in the airway is to generate bronchial secretions and constriction and hence, the inhibition of this action can lead to bronchodilation and fewer secretions. At the cellular level, the diameter of the airways is controlled by the release of acetylcholine into the muscle cells causing them to contract and producing a narrow airway. Thus administration of ipratropium stops the activity of acetylcholine in the smooth muscle preventing the contraction and producing relaxed airways. Possible side effects of using trospium may include bladder pain, back pain, blurred vision, and dry mouth.

Trospium PIS1M1 and Trospium PIIS2M1 are metabolites of Trospium predicted with biotransformer.

The trp operon in E. coli contains five genes that produce proteins that are used in the production of the amino acid tryptophan when needed by the cell. When tryptophan levels in the cell are high, tryptophan binds to the trp operon repressor protein, which activates it. The activated repressor then binds to the operator, preventing RNA polymerase from binding and transcribing the operon. However, when tryptophan concentrations in the cell are low, it doesn't bind to the repressor, preventing it from binding to the operator, and allowing transcription until the terminator after the trpA gene is reached. The trp operon is also regulated by the amount of useable trp tRNA present. Upon start of transcription, the leader peptide, encoded by the trpL gene, will begin to be transcribed. Because this peptide contains two trp residues next to each other, and trp is a relatively uncommon amino acid, if there is a low concentration of trp tRNA in the cell, it can cause the leader peptide to stall during transcription. This allows for the section of mRNA immediately after the stalled ribosome to form the anti-termination hairpin. This hairpin prevents the formation of the terminal hairpin that contains a termination sequence that would stop transcription after the leader peptide. Because the anti-termination hairpin is allowed to form, transcription of the rest of the operon can continue. However, when the cell contains a high concentration of trp tRNA, the transcription does not stall, which allows for the formation of the transcription terminator to form before the rest of the genes in the operon, preveinting their transcription. The trpE and trpD genes encode for anthranilate synthase components 1 and 2 respectively. These combine to create anthranilate synthase, which produces anthranilate and pyruvate from chorismate. The trpC gene encodes the tryptophan biosynthesis protein that takes the anthranilate from the previous protein and converts it in two steps to indole-3-glycerol. Finally, the trpB and trpA genes encode for tryptophan beta and alpha subunits respectively. Two of each subunit come together to form tryptophan synthase. This protein then takes the previous compound, as well as a molecule of L-serine, and catalzes their conversion into tryptophan, as well as water and D-glyceraldehyde-3-phosphate.

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