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Cytochrome P450 2C9 Cytochrome P450 2A6 Retinal dehydrogenase 1 Aldehyde dehydrogenase, dimeric NADP-preferring Retinal dehydrogenase 1 Aldoifosfamide Aldoifosfamide Aldoifosfamide Isophosphamide mustard Isophosphamide mustard 4- Hydroxyifosfamide 4- Ketoifosfamide Ifosfamide O2 NADPH H+ H2O NADP Acrolein NAD H2O Acrylic acid NADH H+ H2O NAD Carboxyifosfamide NADH H+ Heme Cytochrome P450 2B6 Cytochrome P450 3A4 Cytochrome P450 2C8 Cytochrome P450 3A5 Heme Heme Heme Heme Heme Endoplasmic Reticulum Membrane Ifosfamide travels to the liver and is converted to 4-hydroxyifosfamide via various CYP450 enzymes 4-Hydroxyifosfamide can be either converted to 4-ketoifosfamide, which is inactive or it can be turned into it's tautomer aldoifosfamide. Aldoifosfamide is transported into the blood to be delivered to the site of the tumor/cancer cells. Aldoifosfamide in the cancer cell is converted in a non-enzymatic fashion to isophosphamide mustard . In the process of its conversion, acrolein is released which is a cytotoxic irritant. Isophophamide mustard goes into the nucleus and crosslinks guanines causing DNA damage and leading to apoptosis Apoptosis Acrolein is a potent irritant and causes hemorrhagic cystitis. Patients should take MESNA with it to limit the toxicity.
Nucleus Endoplasmic Reticulum CYP2C9 CYP2A6 ALDH1A1 ALDH3A1 ALDH1A1 Aldoifosfamide Aldoifosfamide Aldoifosfamide Isophosphamide mustard Isophosphamide mustard 4- Hydroxyifosfamide 4- Ketoifosfamide Ifosfamide Oxygen NADPH Hydrogen Ion Water NADP Acrolein NAD Water Acrylic acid NADH Hydrogen Ion Water NAD Carboxyifosfamide NADH Hydrogen Ion CYP2B6 CYP3A4 CYP2C8 CYP3A5
CYP2C9 CYP2A6 ALDH1A1 ALDH3A1 ALDH1A1 Aldifo Aldifo Aldifo Isophos Isophos 4Hiff 4kffm Ifosfam O2 NADPH H+ H2O NADP Acrolen NAD H2O AcryliA NADH H+ H2O NAD Caroxyf NADH H+ Heme CYP2B6 CYP3A4 CYP2C8 CYP3A5 Heme Heme Heme Heme Heme Endoplasmic Reticulum Membrane Ifosfamide travels to the liver and is converted to 4-hydroxyifosfamide via various CYP450 enzymes 4-Hydroxyifosfamide can be either converted to 4-ketoifosfamide, which is inactive or it can be turned into it's tautomer aldoifosfamide. Aldoifosfamide is transported into the blood to be delivered to the site of the tumor/cancer cells. Aldoifosfamide in the cancer cell is converted in a non-enzymatic fashion to isophosphamide mustard . In the process of its conversion, acrolein is released which is a cytotoxic irritant. Isophophamide mustard goes into the nucleus and crosslinks guanines causing DNA damage and leading to apoptosis Apoptosis Acrolein is a potent irritant and causes hemorrhagic cystitis. Patients should take MESNA with it to limit the toxicity.
Nucleus Endoplasmic Reticulum CYP2C9 CYP2A6 ALDH1A1 ALDH3A1 ALDH1A1 Aldifo Aldifo Aldifo Isophos Isophos 4Hiff 4kffm Ifosfam O2 NADPH H+ H2O NADP Acrolen NAD H2O AcryliA NADH H+ H2O NAD Caroxyf NADH H+ CYP2B6 CYP3A4 CYP2C8 CYP3A5