Pathways

Acetyl-CoA is an important molecule, which is precursor to HMG CoA, which is a vital component in cholesterol and ketone synthesis. Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent. Acetyl-CoA is made in the mitochondria by metabolizing fatty acids, and the oxidation of pyruvate of acetyl-CoA. When the body has an excess of ATP, the energy in acetyl-Coa can be stored in the form of fatty acids. Acetyl-CoA must cross the mitochondrial membrane to the cytosol, where fatty acid synthesis takes place. Acetyl-CoA is combined with oxalacetic acid by the enzyme citrate synthase, creating citric acid. Citric acid is then transported out of the mitochondria, to the cytosol, where the enzyme citrate lyase converts citric acid back into acetyl-CoA and oxalacetic acid. Malate dehydrogenase reduces oxalacetic acid to malate, which then is either transported back into the mitochondria by the malate-alpha ketoglutarate transporter or oxidized to pyruvate by malic enzyme. Pyruvate can then be transported back into the mitochondria and undergo decarboxylation into oxalacetic acid. Malate can also be used to create NADH by the conversion of malate to oxalacetic acid by malate dehydrogenase.

Acetyl-CoA is an important molecule, which is precursor to HMG CoA, which is a vital component in cholesterol and ketone synthesis. Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent. Acetyl-CoA is made in the mitochondria by metabolizing fatty acids, and the oxidation of pyruvate of acetyl-CoA. When the body has an excess of ATP, the energy in acetyl-Coa can be stored in the form of fatty acids. Acetyl-CoA must cross the mitochondrial membrane to the cytosol, where fatty acid synthesis takes place. Acetyl-CoA is combined with oxalacetic acid by the enzyme citrate synthase, creating citric acid. Citric acid is then transported out of the mitochondria, to the cytosol, where the enzyme citrate lyase converts citric acid back into acetyl-CoA and oxalacetic acid. Malate dehydrogenase reduces oxalacetic acid to malate, which then is either transported back into the mitochondria by the malate-alpha ketoglutarate transporter or oxidized to pyruvate by malic enzyme. Pyruvate can then be transported back into the mitochondria and undergo decarboxylation into oxalacetic acid. Malate can also be used to create NADH by the conversion of malate to oxalacetic acid by malate dehydrogenase.

Acetyl-CoA is an important molecule, which is precursor to HMG CoA, which is a vital component in cholesterol and ketone synthesis. Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent. Acetyl-CoA is made in the mitochondria by metabolizing fatty acids, and the oxidation of pyruvate of acetyl-CoA. When the body has an excess of ATP, the energy in acetyl-Coa can be stored in the form of fatty acids. Acetyl-CoA must cross the mitochondrial membrane to the cytosol, where fatty acid synthesis takes place. Acetyl-CoA is combined with oxalacetic acid by the enzyme citrate synthase, creating citric acid. Citric acid is then transported out of the mitochondria, to the cytosol, where the enzyme citrate lyase converts citric acid back into acetyl-CoA and oxalacetic acid. Malate dehydrogenase reduces oxalacetic acid to malate, which then is either transported back into the mitochondria by the malate-alpha ketoglutarate transporter or oxidized to pyruvate by malic enzyme. Pyruvate can then be transported back into the mitochondria and undergo decarboxylation into oxalacetic acid. Malate can also be used to create NADH by the conversion of malate to oxalacetic acid by malate dehydrogenase.

Tranylcypromine is a non-hydrazine monoamine oxidase inhibitor belonging to the class of antidepressants called MAOIs. This drug is indicated in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in panic and phobic disorders. The monoamine oxidase is an enzyme that catalyzes the oxidative deamination of many amines like serotonin, norepinephrine, epinephrine, and dopamine. There are 2 isoforms of this protein: A and B. The first one is found in cells located in the periphery and breakdown serotonin, norepinephrine, epinephrine, dopamine, and tyramine. The second one, the B isoform, breakdowns phenylethylamine, norepinephrine, epinephrine, dopamine, and tyramine. This isoform is found in the extracellular tissues and mostly in the brain. The mechanism of action of the MAOIs is still not determined, it is thought that they act by increasing free serotonin and norepinephrine concentrations and/or by altering the concentrations of other amines in the CNS. MAO A inhibition is thought to be more relevant to antidepressant activity than the inhibition caused by MAO B. Selective MAO B inhibitors have no antidepressant effects. An overdose of this drug will result in insomnia, restlessness, and anxiety. Hypotension, dizziness, weakness, and drowsiness may occur, progressing in severe cases to extreme dizziness and shock. This drug is administered as an oral tablet.

Tranylcypromine is a non-hydrazine monoamine oxidase inhibitor belonging to the class of antidepressants called MAOIs. This drug is indicated in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in panic and phobic disorders. The monoamine oxidase is an enzyme that catalyzes the oxidative deamination of many amines like serotonin, norepinephrine, epinephrine, and dopamine. There are 2 isoforms of this protein: A and B. The first one is found in cells located in the periphery and breakdown serotonin, norepinephrine, epinephrine, dopamine, and tyramine. The second one, the B isoform, breakdowns phenylethylamine, norepinephrine, epinephrine, dopamine, and tyramine. This isoform is found in the extracellular tissues and mostly in the brain. The mechanism of action of the MAOIs is still not determined, it is thought that they act by increasing free serotonin and norepinephrine concentrations and/or by altering the concentrations of other amines in the CNS. MAO A inhibition is thought to be more relevant to antidepressant activity than the inhibition caused by MAO B. Selective MAO B inhibitors have no antidepressant effects. An overdose of this drug will result in insomnia, restlessness, and anxiety. Hypotension, dizziness, weakness, and drowsiness may occur, progressing in severe cases to extreme dizziness and shock. This drug is administered as an oral tablet.

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

Trastuzumab is a recombinant humanized IgG1 monoclonal antibody to the human epidermal growth factor receptor 2 (HER2) that is administered intravenously for the treatment of HER2 positive breast cancer (adjuvant therapy), metastatic HER2-positive breast cancer and HER2 positive gastric cancer. HER-2 is over expressed in these cancer cells and therefore trastuzumab targets these cancer cells over normal cells. The HER-2 receptor is a transmembrane tyrosine kinase receptor that consists of an extracellular ligand-binding domain, a transmembrane region, and an intracellular or cytoplasmic tyrosine kinase domain. HER-2 forms heterodimers with other EGFR proteins such as HER-1, HER-2 or HER-4 when they bind to ligands or may form homodimers with other HER-2 proteins. Following dimerization, transphosphorylation/ autophosphorylation of the tyrosine residues on the cytoplasmic domain of these receptors occurs. This activates a number of intracellular signaling pathways such as the raf/MAPK pathway, PI3K/akt pathway and PLC/PKC pathway. The activation of these pathways recruits nuclear factors that regulate genes involved in cell-cycle progression, proliferation, growth and survival. Trastuzumab binds to the extracellular domain of HER-2 and prevents dimerization. Inhibiting dimerization prevents the activation of the downstream intracellular signaling cascades initiated by the HER proteins. This therefore prevents the gene regulation necessary to promote cell-cycle progression, proliferation, growth and survival. Nuclear transcription affected by these pathways cannot occur, and therefore essential proteins are not produced. This causes cell cycle arrest and suppresses cell growth and proliferation and eventually the cancer cell undergoes apoptosis. Side effects such as headache, chills, cough, back pain, weakness and fatigue, upper respiratory symptoms including rhinitis and pharyngitis, angioedema, cardiotoxicity, anaphylaxis and GI disturbances including nausea, vomiting, abdominal pain, diarrhea.

Trastuzumab is an anti-EGFR drug used in the treatment of HER2-positive breast cancer. EGFR is linked multiple signalling pathways involved in tumour growth and angiogenesis such as the Ras/Raf pathway and the PI3K/Akt pathways. These pathways ultimately lead to the activation of transcription factors such as Jun, Fos, and Myc, as well as cyclin D1, which stimulates cell growth and mitosis. Uncontrolled cell growth and mitosis leads to cancer. Trastuzumab acts as an anticancer drug by binding to the extracellular domain of the EGFR and preventing its activation by epidermal growth factor. This in turn inhibits downstream signalling and prevents tumour growth.