tailieunhanh - Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

(BQ) Part 2 book “Marks’ basic medical biochemistry: A clinical approach’ has contents: Gluconeogenesis and maintenance of blood glucose levels, digestion and transport of dietary lipids, liver metabolism, blood plasma proteins, coagulation and fibrinolysis, the biochemistry of the erythrocyte and other blood cells, and other contents. | 24 Oxygen Toxicity and Free Radical Injury O2 is both essential to human life and toxic. We are dependent on O2 for oxidation reactions in the pathways of adenosine triphosphate (ATP) generation, detoxification, and biosynthesis. However, when O2 accepts single electrons, it is transformed into highly reactive oxygen radicals that damage cellular lipids, proteins, and DNA. Damage by reactive oxygen radicals contributes to cellular death and degeneration in a wide range of diseases (Table ). Radicals are compounds that contain a single electron, usually in an outside orbital. Oxygen is a biradical, a molecule that has two unpaired electrons in separate orbitals (Fig. ). Through a number of enzymatic and nonenzymatic processes that routinely occur in cells, O2 accepts single electrons to form reactive oxygen species (ROS). ROS are highly reactive oxygen radicals, or compounds that are readily converted in cells to these reactive radicals. The ROS formed by reduction of O2 are the radical superoxide (O2¯ ), the nonradical hydrogen peroxide (H2O2 ), and the hydroxyl radical (OH• ). ROS may be generated nonenzymatically, or enzymatically as accidental byproducts or major products of reactions. Superoxide may be generated nonenzymatically from CoQ, or from metal-containing enzymes (., cytochrome P450, xanthine oxidase, and NADPH oxidase). The highly toxic hydroxyl radical is formed nonenzymatically from superoxide in the presence of Fe3 or Cu by the Fenton reaction, and from hydrogen peroxide in the Haber–Weiss reaction. Oxygen radicals and their derivatives can be deadly to cells. The hydroxyl radical causes oxidative damage to proteins and DNA. It also forms lipid peroxides and malondialdehyde from membrane lipids containing polyunsaturated fatty acids. In some cases, free radical damage is the direct cause of a disease state (., tissue damage initiated by exposure to ionizing radiation). In neurodegenerative diseases, such as Parkinson’s disease, or