Biochemistry Online: An Approach Based on Chemical Logic

Biochemistry Online





Learning Goals/Objectives for Chapter 8A:  After class and this reading, students will be able to

  • explain why oxidation reactions with ground state dioxygen have a high enough activation energy to make the reactions, although thermodynamically favored, kinetically slow
  • explain, using molecular orbital diagrams the difference between triplet and singlet dioxygen
  • using molecular orbital diagrams and Lewis structures, describe the chemical properties of the reduction products of dioxygen (superoxide, peroxide, and water)
  • explain the ways that biological systems use to enhance dioxygen activity and reduce the effects of reactive oxygen species (ROS) such as superoxide and peroxide
  •  write chemical reactions and mechanisms when appropriate for some reactions of triplet and singlet dioxygen, superoxide, peroxide and the hydroxy free radical
  • describe typical reaction of ROS with lipids, proteins, and nucleic acids and data to support the involvement of ROS in complex diseases and aging.
  • Briefly contrast the production and biological activities of ROS and reactive nitrogen intermediates (RNIs)

A10.  Hypoxia

We have spend much time studying how the body deals with and utilizes the toxic byproducts of dioxygen reduction.  What happens when the body doesn't get enough dioxygen - a condition call anoxia (no dioxygen) or hypoxia (too little dioxygen)?  This might occur in muscles undergoing vigorous exercise, and in the brain and heart when clots occlude blood flow to these organs (as occurs in most strokes and heart attacks).  Under low dioxygen concentrations, a family of protein transcription factors  called hypoxia-inducible factor (HIF) become activated.  The functional proteins appears to be a dimer of HIF-α and HIF-β.  In contrast to the concentration of the beta form,  the activity of HIF-α is increased under low dioxygen concentrations.  HIF-α concentration is regulated not at the transcriptional level, but through proteolysis of the protein.  In the presence of abundant dioxygen, HIF-α is hydroxylated at two Pro residues by the enzyme prolyl hydroxlase.  This  post-translational modification targets the protein for proteolysis (through ubiquitination by the VHL protein and subsequent cleavage by the proteasome).  A second independent pathway in rapidly growing tissue leads to increased expression of HIF-α even in the presence of dioxygen.  This could be beneficial to cells since rapidly growing tissue, especially tumor cells, might  be expected to experience low oxygen conditions. 

Figure:  Cell response to hypoxia


Return to Chapter 8A:  The Chemistry of Dioxygen Sections

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Archived version of full Chapter 8A:  The Chemistry of Dioxygen


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