Pathways

Metoprolol goes through significant first-pass hepatic metabolism which covers around 50% of the administered dose. The metabolism of metoprolol is mainly driven by the activity of CYP2D63 and to a lesser extent due to the activity of CYP3A4. The metabolism of metoprolol is mainly represented by reactions of hydroxylation and O-demethylation.

Metrifonate is an acetylcholinesterase inhibitor, a prodrug that is non-enzymatically converted into its active form Dichlorvos. While binding to acetylcholinesterase it prevents the breakdown of acetylcholine, allowing the neurotransmitter to interact with the receptors that help aid memory and cognition in patients with dementia and alzheimer's disease.

Metabolites of Metronidazole are predicted with biotransformer.

The mevalonate pathway, also known as the isoprenoid pathway, plays an essential role in creating the chemicals needed for many plants to function. This pathway, combined with the MEP/DOXP pathway give many plants their scents, such as cinnamon and ginger, and are responsible for the red colour in tomatoes. The pathway begins with acetyl-CoA, having come from the glycolysis pathway. Acetyl-CoA immediately becomes acetoacetyl-CoA through the enzyme acetyl-CoA acetyltransferase 1/2. Combined, acetoacetyl-CoA and acetyl-CoA react with hydroxymethylglutaryl-CoA synthase to create 3-hydroxy-3methylglutaryl-CoA. From here, this compound is catalyzed by 3-hydroxy-3-methylglutaryl-coenzyme A reductase 1 and becomes (R)-mevalonate. Mevalonate is paired with mevalonate kinase to produce mevalonic acid-5P. In turn, mevalonic acid-5P reacts with phosphomevalonate kinase, and entering the peroxisome and becoming (R)-mevalonic acid-5-pyrophosphate. Remaining in the peroxisome, diphosphomevalonate decarboxylase MVD1 is used alongside (R)-mevalonic acid-5-pyrophosphate to create isopentenyl pyrophosphate, bringing the pathway into the chloroplast. Dimethylallylpyrophosphate is produced after isopentenyl pyrophosphate and isopentenyl diphosphate delta-isomerase II team up to catalyze it. Dimethylallylpyrophosphate then joins forces with isopentenyl again, this time adding geranylgeranyl pyrophosphate synthase 6 and moving into the mitochondria to produce geranyl-PP. This is followed by monoterpenoid biosynthesis.

The Mevalonate Pathway is a necessary pathway that occurs in archaea, eukaryotes and select bacteria. It has mainly been studied with regard to cholesterol biosynthesis and how it relates to cardiovascular disease in humans, but has recently garnered attention for its many other essential roles within human pathology. The pathway begins in the cytoplasm with acetyl-CoA and acetoacetyl-CoA, which interact with acetyl-CoA acetyltransferase, coenzyme A and water to synthesize hydroxymethylglutaryl-CoA synthase. In turn, this synthase teams up with coenzyme A and a hydrogen ion in the endoplasmic reticulum to create 3-hydroxy-3-methylglutaryl-CoA. 3-Hydroxy-3-methylglutaryl-CoA then pairs with 2NADPH, 2 hydrogen ions and is catalyzed by 3-hydroxy-3-methylglutaryl-coenzyme A reductase to produce (R)-mevalonate, also producing byproducts CoA and NADP. Exiting the endoplasmic reticulum, and entering the peroxisome, (R)-mevalonate uses the help of ATP and mevalonate kinase to create mevalonic acid (5P). This piece is especially important to the human species as decreased activity of the enzyme mevalonate kinase has been found to be a direct link to two auto-inflammatory disorders: MVA and HIDS. Using phosphomevalonate kinase and ATP, the pathway re-enters the cytoplasm and mevalonic acid (5P) converts to (R)-mevalonic acid-5-pyrophosphate and ADP. (R)-mevalonic acid-5-pyrophosphate, ATP and diphosphomevalonate decarboxylase work together to create phosphate, carbon dioxide, ADP and isopentenyl pyrophosphate. Re-entering the peroxisome, isopentenyl diphosphate delta isomerase 1 is waiting to propel isopentenyl pyrophosphate into dimethylallylpyrophosphate. This pushes the pathway back into the cytoplasm, where another isopentenyl pyrophosphate molecule and the enzyme farnesyl pyrophosphate synthase create pyrophosphate and geranyl-PP. Yet another isopentenyl pyrophosphate molecules works with farnesyl pyrophosphate synthase to produce pyrophosphate and farnesyl pyrophosphate. Now in the endoplasmic reticulum membrane, 2 farnesyl pyrophosphate molecules with the help of NADPH and a hydrogen ion catalyze with squalene synthase and create squalene. This is an important first step in the specific hepatic cholesterol pathway. Remaining in the endoplasmic reticulum membrane, squalene, FMNH, oxygen and squalene monooxygenase synthesize (S)-2,3-epoxysqualene. This comes along with the byproducts of flavin mononucleotide, a hydrogen ion and water. In the final reaction within this pathway, lanesterol synthase converts (S)-2,3-epoxysqualene to lanosterin. Not pictured in this pathway, lanosterin will eventually be converted to cholesterol, an important part of many functions in the human body.

The mevalonate pathway, also known as the isoprenoid pathway, plays an essential role in creating the chemicals needed for many plants to function. This pathway, combined with the MEP/DOXP pathway give many plants their scents, such as cinnamon and ginger, and are responsible for the red colour in tomatoes. The pathway begins with acetyl-CoA, having come from the glycolysis pathway. Acetyl-CoA immediately becomes acetoacetyl-CoA through the enzyme acetyl-CoA acetyltransferase 1/2. Combined, acetoacetyl-CoA and acetyl-CoA react with hydroxymethylglutaryl-CoA synthase to create 3-hydroxy-3methylglutaryl-CoA. From here, this compound is catalyzed by 3-hydroxy-3-methylglutaryl-coenzyme A reductase 1 and becomes (R)-mevalonate. Mevalonate is paired with mevalonate kinase to produce mevalonic acid-5P. In turn, mevalonic acid-5P reacts with phosphomevalonate kinase, and entering the peroxisome and becoming (R)-mevalonic acid-5-pyrophosphate. Remaining in the peroxisome, diphosphomevalonate decarboxylase MVD1 is used alongside (R)-mevalonic acid-5-pyrophosphate to create isopentenyl pyrophosphate, bringing the pathway into the chloroplast. Dimethylallylpyrophosphate is produced after isopentenyl pyrophosphate and isopentenyl diphosphate delta-isomerase II team up to catalyze it. Dimethylallylpyrophosphate then joins forces with isopentenyl again, this time adding geranylgeranyl pyrophosphate synthase 6 and moving into the mitochondria to produce geranyl-PP. This is followed by monoterpenoid biosynthesis.