Pathways

The biosynthesis of thiamin begins with a PRPP being degraded by reacting with a water molecule and an L-glutamine through a amidophosphoribosyl transferase resulting in the release of an L-glutamate, a diphosphate and a 5-phospho-beta-d-ribosylamine(PRA). The latter compound, PRA, is further degrade through a phosphoribosylamine glycine ligase by reacting with a glycine and an ATP. This reaction results in the release of a hydrogen ion, an ADP, a phosphate and a N1-(5-phospho-beta-d-ribosyl)glycinamide(GAR). GAR can be metabolized by two different phosphoribosylglycinamide formyltransferase. GAR reacts with a N10-formyl tetrahydrofolate, in this case 10-formyl-tetrahydrofolate mono-L-glutamate, through a phosphoribosylglycinamide formyltransferase 1 resulting in the release of a hydroge ion, a tetrahydrofolate and a N2-formyl-N1-(5-phospho-Beta-D-ribosyl)glycinamide(FGAR). On the other hand, GAR can react with a formate and an ATP molecule through a phosphoribosylglycinamide formyltransferase 2 resulting in a release of a ADP, a phosphate, a hydrogen ion and a FGAR. The FGAR compound gets degraded by interacting with a water molecule, an L-glutamine and an ATP molecule thorugh a phosphoribosylformylglycinamide synthase resulting in the release of a L-glutamate, a phosphate, an ADP molecule, a hydrogen ion and a 2-(formamido)-N1-(5-phopho-Beta-D-ribosyl)acetamidine (FGAM). This compound is further degraded by reacting with an ATP molecule through a phosphoribosylformylglycinamide cyclo-ligase resulting in the release of a phosphate, an ADP, a hydrogen ion and a 5-amino-1-(5-phospho-beta-d-ribosyl)imidazole (AIR). The AIR molecule is degraded by reacting with a S-adenosyl-L-methionine through a HMP-P synthase resulting in the release of 3 hydrogen ions, a carbon monoxide, a formate molecule, L-methionine, 5'-deoxyadenosine and 4- amino-2-methyl-5-phophomethylpyrimidine (HMP-P). This resulting compound is phosphorylated thorugh a ATP driven phosphohydroxymethylpyrimidine kinase resulting in the release of an ADP and 4-amino-2-methyl-5-diphosphomethylpyrimidine (HMP-PP). The resulting compound interacts with a thiazole tautomer and 2 hydrogen ion through a Thiamine phosphate synthase resulting in the release of a pyrophosphate, a carbon dioxide molecule and Thiamin phosphate. This compound is phosphorylated through an ATP driven thiamin monophosphate kinase resulting in a release of an ADP and a thiamin diphosphate.

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

Thiazinamium is a first-generation phenothiazine H1-antihistamine. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Reducing the activity of the NF-κB immune response transcription factor through the phospholipase C and the phosphatidylinositol (PIP2) signalling pathways also decreases antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Furthermore, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release. First-generation antihistamines readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects (e.g. nervousness and insomnia). Second-generation antihistamines are more selective for H1-receptors of the peripheral nervous system (PNS) and do not cross the blood-brain barrier. Consequently, these newer drugs elicit fewer adverse drug reactions.

This pathway demonstrate the biosynthesis of thiazole moiety in E.coli K-12 strain and Salmonella enterica serovar Typhimurium. L-Tyrosine is generated from tyrosine biosynthesis. With S-Adenosylmethionine and NADPH, L-Tyrosine can be catalyzed into four different small molecules: 4-methylcatechol, dehydroglycine, 5'-deoxyadenosine and L-methionine as well as NADP by dehydroglycine synthase (encoded by thiH gene). Meanwhile, 1-deoxyxylulose-5-phosphate synthase (encoded by dxs gene) catalyzes pyruvic acid and D-Glyceraldehyde 3-phosphate into 1-Deoxy-D-xylulose 5-phosphate. The final reaction of the pathway is facilitated by thiazole synthase (encoded by thiG and thiH), which require a thiocarboxy-[ThiS-Protein], 1-deoxy-D-xylulose 5-phosphate and 2-iminoacetate to form 2-((2R,5Z)-2-Carboxy-4-methylthiazol-5(2H)-ylidene)ethyl phosphate for Thiamin Diphosphate Biosynthesis, as well as a ThiS sulfur-carrier protein and water.

Thiethylperazine is in the class of the piperazine - phenothiazines which are a class of first generation antipsychotic medications. Phenothiazines are generally dopamine receptor antagonists. Thiethylperazine' s antipsychotic effect is due to antagonism at dopamine and serotonin type 2 receptors, with greater activity at serotonin 5-HT2 receptors than at dopamine type-2 receptors. This may explain the lack of extrapyramidal effects. Thiethylperazine does not appear to block dopamine within the tubero-infundibular tract, explaining the lower incidence of hyperprolactinemia than with typical antipsychotic agents or risperidone. It is a sedating antihistamine used as an antiemetic agent for the control of nausea and vomiting associated with surgical procedures.

Thiethylperazine is in the class of the piperazine - phenothiazines which are a class of first generation antipsychotic medications. Phenothiazines are generally dopamine receptor antagonists. Thiethylperazine' s antipsychotic effect is due to antagonism at dopamine and serotonin type 2 receptors, with greater activity at serotonin 5-HT2 receptors than at dopamine type-2 receptors. This may explain the lack of extrapyramidal effects. Thiethylperazine does not appear to block dopamine within the tubero-infundibular tract, explaining the lower incidence of hyperprolactinemia than with typical antipsychotic agents or risperidone. It is a sedating antihistamine used as an antiemetic agent for the control of nausea and vomiting associated with surgical procedures.

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