Pathways

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

Terpenoids are a class of organic compounds made up of 5 carbon isoprene units. There are two pathways, melvalonate and MEP/DOXP, that synthesize the terpenoid backbone components. Both of these create isopentenyl pyrophosphate, which may then react using isopentenyl diphosphate isomerase in the chloroplast to form dimethylallylprophosphate. This molecule is also produced by the MEP/DOXP pathway. Isopentenyl pyrophosphate and dimethylallylprophosphate can react with geranylphosphate synthase in the mitochondrion to form geranyl-pyrophosphate, the main compound used in monoterpenoid biosynthesis. Geranyl-pyrophosphate may also react again with isopentenyl pyrophosphate using solanesyl diphosphate synthase 2 in the chloroplast to form solanesyl pyrophosphate, a potential end product of this pathway. Alternately, they can react with (2E,6E)-farnesyl diphosphate synthase, also in the mitochondrion, to form farnesyl phosphate. Farnesyl pyrophosphate may then be used as the main precursor in the sesquiterpenoid and triterpenoid biosynthesis pathways. It may also react with geranylgeranyl pyrophosphate 6 in the mitochondrion to form geranylgeranyl pyrophosphate. Geranylgeranyl pyrophosphate can react with isopentenyl pyrophosphate, catalyzed by solanesyl diphosphate syntahse 2, again in the chloroplast, to form solanesyl pyrophosphate. Aside this reaction, it can be converted by geranylgeranyl dehydrogenase in the chloroplast to form phytyl pyrophosphate, another end product of this pathway. Farnesyl pyrophosphate can additionally react using an undecaprenyl pyrophosphate synthetase family protein as a catalyst in order to form dehydrolichol pyrophosphate, or with the protein farnesyltransferase complex, which will add a protein-cysteine to the farnesyl pyrophosphate, which in turn loses its pyrophosphate group. The S-farnesyl protein then reacts with either CAAX prenyl protease 1 or 2 in the endoplasmic reticulum membrane to form protein C-terminal S-farnesyl-L-cysteine. This complex then reacts using protein-S-isoprenylcysteine O-methyltransferase B, still in the endoplasmic reticulum membrane, to form protein-C-terminal S-farnesyl-L-cysteine methyl ester. This reaction may be reversed by isoprenylcysteine alpha-carbonyl methylesterase, yet again in the endoplasmic reticulum membrane. Alternately, through an as of yet unknown reaction, the protein may be removed, as well as several other structure changes, leaving farnesylcysteine. In the lysosome, farnesylcysteine can be catalyzed by farnesylcysteine to remove the cysteine group, leaving behind farnesal. Then, a NAD-binding Rossman-fold superfamily protein can catalyze its transformation into farnesol. Finally, within the chloroplast, farnesol can be catalyzed by farnesol kinase to form farnesyl phosphate, the final product of this pathway.

From glycolysis and the mevalonate pathway, diphosphomevalonic acid can be reacted with ATP to produce isopentenyl diphosphate which can be used in many reactions due to it's phosphate groups. Isopentenyl can be converted into geranyl pyrophosphate through two different paths, with one having an intermediate of dimethylallylpyrophosphate. Geranyl pyrophosphate itself can be used in monoterpenoid biosynthesis but more importantly, it can converted into (E,E)- farnesyl diphosphate through farnesyl pyrophosphate synthase. With (E,E)-farnesyl diphosphate and isopentenyl diphosphate, many reactions can take place depending on the number of substrates are used and how many phosphate groups are to be transferred. The products from the reactions are usually substrates for other biosynthesis pathways like N-glycan biosynthesis, carotenoid biosynthesis, diterpenoid biosynthesis, steroid biosynthesis and ubiquinone and other terpenoid quinone biosynthesis pathways. (E,E) farnesyl diphosphate can also be combined with a cysteine protein to make S-farnesyl protein. S-Farnesyl protein can have the c-terminal removed and then can be trans methylated by S-adenosylmethionine to eventually make farnesylcysteine. Through unknown processes farnesylcysteine can be converted can converted back to (E,E) farnesyl diphosphate, but not all the enzymes are known yet.

The biosynthesis of steroids begins with acetyl coa being turned into acetoacetyl through a acetoacetyl CoA thiolase. Acetoacetyl -CoA reacts with an acetyl-CoA and water through a 3-hydroxy 3-methylglutaryl coenzyme A synthase resulting in the release of coenzyme A, hydrogen ion and (S)-3-hydroxy-3-methylglutaryl-CoA. The latter compound reacts with NADPH and a hydrogen ion through a 3-hydroxy-3-methylglutaryl-coenzyme A resulting in the release of coenzyme A , NADP and mevalonate. Mevalonate is then phosphorylated through an ATP driven kinase mevalonate kinase resulting in the release of ADP, hydrogen ion and mevalonate 5-phosphate. The latter compound is phosphorylated through an ATP driven kinase, phosphomevalonate kinase resulting in the release of ADP and mevalonate diphosphate. This latter compound then reacts with an ATP driven mevalonate diphosphate decarboxylase resulting in the release of ADP, carbon dioxide, a phosphate and a isopentenyl diphosphate. The latter compound can be isomerized into dimethylallyl diphosphate or reacth with a dimethylallyl diphosphate to produce geranyl diphosphate. Geranyl diphosphate reacts with a isopentenyl through a farnesyl diphosphate synthase resulting in the release of diphosphate and farnesyl diphosphate. Farnesyl diphosphate has three different fates: 1.-Producing hexaprenyl diphosphate in the mitocondrial inner membrane by reacting with 3 isopentenyl diphosphate 2.-Producing geranylgeranyl diphosphate in the cytoplasm by reacting with one isopentenyl diphosphate 3.-Producing a dolichol precursor in the ER by reacting with 13 isopentenyl diphosphates.

The biosynthesis of steroids begins with acetyl coa being turned into acetoacetyl through a acetoacetyl CoA thiolase. Acetoacetyl -CoA reacts with an acetyl-CoA and water through a 3-hydroxy 3-methylglutaryl coenzyme A synthase resulting in the release of coenzyme A, hydrogen ion and (S)-3-hydroxy-3-methylglutaryl-CoA. The latter compound reacts with NADPH and a hydrogen ion through a 3-hydroxy-3-methylglutaryl-coenzyme A resulting in the release of coenzyme A , NADP and mevalonate. Mevalonate is then phosphorylated through an ATP driven kinase mevalonate kinase resulting in the release of ADP, hydrogen ion and mevalonate 5-phosphate. The latter compound is phosphorylated through an ATP driven kinase, phosphomevalonate kinase resulting in the release of ADP and mevalonate diphosphate. This latter compound then reacts with an ATP driven mevalonate diphosphate decarboxylase resulting in the release of ADP, carbon dioxide, a phosphate and a isopentenyl diphosphate. The latter compound can be isomerized into dimethylallyl diphosphate or reacth with a dimethylallyl diphosphate to produce geranyl diphosphate. Geranyl diphosphate reacts with a isopentenyl through a farnesyl diphosphate synthase resulting in the release of diphosphate and farnesyl diphosphate. Farnesyl diphosphate has three different fates: 1.-Producing hexaprenyl diphosphate in the mitocondrial inner membrane by reacting with 3 isopentenyl diphosphate 2.-Producing geranylgeranyl diphosphate in the cytoplasm by reacting with one isopentenyl diphosphate 3.-Producing a dolichol precursor in the ER by reacting with 13 isopentenyl diphosphates.

The biosynthesis of steroids begins with acetyl coa being turned into acetoacetyl through a acetoacetyl CoA thiolase. Acetoacetyl -CoA reacts with an acetyl-CoA and water through a 3-hydroxy 3-methylglutaryl coenzyme A synthase resulting in the release of coenzyme A, hydrogen ion and (S)-3-hydroxy-3-methylglutaryl-CoA. The latter compound reacts with NADPH and a hydrogen ion through a 3-hydroxy-3-methylglutaryl-coenzyme A resulting in the release of coenzyme A , NADP and mevalonate. Mevalonate is then phosphorylated through an ATP driven kinase mevalonate kinase resulting in the release of ADP, hydrogen ion and mevalonate 5-phosphate. The latter compound is phosphorylated through an ATP driven kinase, phosphomevalonate kinase resulting in the release of ADP and mevalonate diphosphate. This latter compound then reacts with an ATP driven mevalonate diphosphate decarboxylase resulting in the release of ADP, carbon dioxide, a phosphate and a isopentenyl diphosphate. The latter compound can be isomerized into dimethylallyl diphosphate or reacth with a dimethylallyl diphosphate to produce geranyl diphosphate. Geranyl diphosphate reacts with a isopentenyl through a farnesyl diphosphate synthase resulting in the release of diphosphate and farnesyl diphosphate. Farnesyl diphosphate has three different fates: 1.-Producing hexaprenyl diphosphate in the mitocondrial inner membrane by reacting with 3 isopentenyl diphosphate 2.-Producing geranylgeranyl diphosphate in the cytoplasm by reacting with one isopentenyl diphosphate 3.-Producing a dolichol precursor in the ER by reacting with 13 isopentenyl diphosphates.

Terpenoids, also known as isoprenoids, are a large class of natural products consisting of isoprene (C5) units. There are two biosynthetic pathways, the mevalonate pathway, and the non-mevalonate pathway or the MEP/DOXP pathway, for the terpenoid building blocks: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). The action of prenyltransferases then generates higher-order building blocks: geranyl diphosphate (GPP), farsenyl diphosphate (FPP), and geranylgeranyl diphosphate (GGPP), which are the precursors of monoterpenoids (C10), sesquiterpenoids (C15), and diterpenoids (C20), respectively. Condensation of these building blocks gives rise to the precursors of sterols (C30) and carotenoids (C40). The MEP/DOXP pathway is absent in higher animals and fungi, but in green plants, the MEP/DOXP and mevalonate pathways co-exist in separate cellular compartments. The MEP/DOXP pathway, operating in the plastids, is responsible for the formation of essential oil monoterpenes and linalyl acetate, some sesquiterpenes, diterpenes, and carotenoids and phytol. The mevalonate pathway, operating in the cytosol, gives rise to triterpenes, sterols, and most sesquiterpenes.