Pathways

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

Carbon fixation is the process where inorganic carbon, usually in the form of carbon dioxide, is converted into organic molecules. The carbon fixation pathway in Arabidopsis thaliana consists of 3 cycles: Reductive pentose phosphate cycle (Calvin-Benson cycle), C4-dicarboxylic acid cycle and crassulacean acid metabolism. The Calvin-Benson cycle involves the light-independent reaction of photosynthesis and takes place through three general steps (carbon fixation, reduction and regeneration). Plants which live in unfavorable conditions like hot and dry climates have adapted to fix carbon dioxide through alternative cycles before it can move into the Calvin-Benson cycle. The C4-dicarboxylic acid cycle and the crassulacean acid metabolism (CAM) cycle are these alternative pathways. The C4-dicarboxylic acid cycle efficiently fixes carbon dioxide at low concentrations so the plants do not have to open their stomata too often. Plants with the CAM cycle open their stomata to fix CO2 only at night and stores it in an organic form. During the day, when the stomata is closed, the carbon dioxide is removed from the stored organic form and enters the Calvin-Benson cycle. In the Calvin-Benson cycle, carbon fixation occurs when ribulose bisphosphate carboxylase converts ribulose-1,5-bisphosphate, carbon dioxide and water into glycerate-3-phosphate. Ribulose-1,5-bisphophate is also linked to the glyoxylate and dicarboxylate metabolism pathway which is involved in forming glycerate-3-phosphate. The reduction step involves phosphoglycerate kinase-2 converting glycerate-3-phosphate into 1,3-bisphosphoglycerate, using ATP. Glyceraldehyde-3-phosphate dehydrogenase then converts 1,3-bisphosphoglycerate into glyceraldehyde-3-phosphate, using NADPH. Some glyceraldehyde-3-phosphate may go into the cytoplasm to form compounds used by the plant. The regeneration step includes reforming the ribulose-1,5-bisphosphate so more carbon fixation can occur. Glyceraldehyde-3-phosphate is converted into fructose-1,6-bisphosphate using fructose bisphosphate aldolase. Fructose 1,6-bisphosphatase then converts fructose-1,6-bisphosphate into fructose-6-phosphate. Fructose-6-phosphate along with glyceraldehyde-3-phosphate can then form erythrose-4-phosphate and xyulose-5-phoshphate through transketolase-2. Glyceraldehyde-3-phosphate can also form glycerone phosphate (linked to the gluconeogenesis cycle which is connected to starch formation) through triosephosphate isomerase. Glycerone phosphate and erythrose-4-phosphate together forms sedoheptulose 1,7-bisphosphate through fructose-bisphosphate aldolase. Sedoheptulose 1,7-bisphosphatase creates sedoheptulose 7-phosphate from sedoheptulose 1,7-bisphosphate. Sedoheptulose 7-phosphate and glyceraldehyde-3-phosphate forms ribose-5-phoshphate and xyulose-5-phosphate. Ribose-5-phosphate and xyulose-5-phosphate can from ribulose-5-phosphate using ribose-5-phosphate isomerase and ribulose phosphate-3 epimerase respectively. Finally, ribulose-1,5-bisphosphate is regenerated from ribulose-5-phosphate using phosphoribulokinase. The C4-dicarboxylic acid pathway fixes carbon dioxide through phosphoenolpyruvate carboxylase-1, which converts phosphoenolpyruvate into oxaloacetate. Oxaloacetate forms malate with chloroplastic malate dehydrogenase. Oxaloacetate can also form aspartate through aspartate aminotransferase, and aspartate forms oxaloacetate through that same enzyme. The oxaloacetate can produce malate through cytoplasmic malate dehydrogenase. The oxaloacetate can regenerate phosphoenolpyruvate and carbon dioxide (which enters the Calvin-Benson cycle) through phosphoenolpyruvate carboxykinase. The malate formed is stored in the bundle-sheath cells and can be broken down to release carbon dioxide which enters the Calvin-Benson cycle. This occurs through mitochondrial NAD-dependent malic enzyme-1 and chloroplastic NADP-dependent malic enzyme-4 which form pyruvate and carbon dioxide. The pyruvate formed in the mitochondria goes on to form alanine through alanine aminotransferase and alanine forms pyruvate through that same enzyme which goes into the chloroplast. Pyruvate in the chloroplast then regenerates phosphoenolpyruvate through pyruvate, phosphate dikinase-1. The CAM cycle fixes carbon dioxide in the atmosphere using phosphoenolpyruvate carboxylase-1 to convert phosphoenolpyruvate into oxaloacetate. Oxaloacetate then uses malate dehydrogenase to form malate which is stored in cell vacuoles. In the day, when the stomata are closed, malate is broken down into pyruvate through NADP-dependent malic enzyme-4. This process releases the carbon dioxide which enters the Calvin-Benson cycle. Pyruvate then reforms the phosphoenolpyruvate by pyruvate, phosphate dikanse-1. The phosphoenolpyruvate is linked to the glycolysis/gluconeogenesis pathway which is involved in forming starch.

Carbinoxamine is a first-generation ethanolamine 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.

Carbinoxamine is an 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. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. 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. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. Allergies causes blood vessel dilation which causes swelling (edema) and fluid leakage. Carbinoxamine also inhibits the H1 histamine receptor on bronchiole smooth muscle myocytes. This normally activates the Gq signalling cascade which activates phospholipase C which catalyzes the production of Inositol 1,4,5-trisphosphate (IP3) and Diacylglycerol (DAG). Because of the inhibition, IP3 doesn't activate the release of calcium from the sarcoplasmic reticulum, and DAG doesn't activate the release of calcium into the cytosol of the endothelial cell. This causes a low concentration of calcium in the cytosol, and it, therefore, cannot bind to calmodulin.Calcium bound calmodulin is required for the activation of myosin light chain kinase. This prevents the phosphorylation of myosin light chain 3, causing an accumulation of myosin light chain 3. This causes muscle relaxation, opening up the bronchioles in the lungs, making breathing easier.