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INTRODUCTION
Body_ID: HC035001
The element oxygen (O2) is essential for the life of aerobic organisms. Although it is highly reactive in combustion reactions at high temperature, oxygen is relatively inert at body temperature; it has a high activation energy for oxidation reactions. This is fortunate, otherwise we might spontaneously combust. About 90% of our O2 usage is committed to oxidative phosphorylation. Enzymes that use O2 for hydroxylation and oxygenation reactions use another fraction of about 10%. A residual fraction, about 1%, is converted to reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, which are inherently toxic, reactive forms of oxygen. ROS are important in metabolism - some enzymes use H2O2 as a substrate - and they play a role in regulation of metabolism and in immunological defenses against infection. However, ROS are also a source of chronic damage to tissue biomolecules. One of the risks of harnessing O2 as a substrate for energy metabolism is that we may, and do, get burned. For this reason, we have a range of antioxidant defenses that protect us against ROS. This chapter will deal with the biochemistry of reactive oxygen, the mechanisms of formation and detoxification of ROS, and their role in human biology.
Body_ID: P035002
IRON OVERLOAD INCREASES RISK FOR DIABETES AND CARDIOMYOPATHY
Body_ID: B035001
Patient with hematologic disorders such as hereditary hemochromatosis, thalassemias and sickle cell disease, or who receive frequent blood transfusions, gradually develop iron overload, a condition that increases the risk for development of cardiomyopathy and diabetes. The heart and β-cells are iron-rich in the mitochondria. The development of secondary disease in iron overload is considered the result of iron-mediated enhancement of mitochondrial ROS production in these tissues. Mutations in the mitochondrial genome may lead to progressive mitochondrial dysfunction.
Body_ID: PB35001
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