LECTURE NOTES # 15 CELLULAR RESPIRATION

I. Introduction - Since there are so many details given in the consideration of cellular respiration, I am introducing a new format in the Lecture Notes which begins with instructional  and performance objectives before the introduction of the material.  This should form a framework on which you can build some of the details of this complex process.

II. INSTRUCTIONAL OBJECTIVES

  (1) Conceptual Objectives

  • Know that most of the production of ATP results from cellular respiration which occurs in mitochondria.
  • Describe the process of oxidative/reductive phosphorylation leading to the formation of ATP.
  • Summarize the role of the Krebs Citric Acid Cycle in both catabolism and anabolism.
  • Know the importance of the Urea Cycle and describe its essential role.

  (2) Performance Objectives

  • Define metabolism, including catabolism and anabolism.
  • Know the structure of the mitochondrium and describe the function of each region.
  • Summarize the major reactions of the Krebs Citric Cycle
  • Be able to follow the fate of a carbon atom from glucose to carbon dioxide
  • Discuss the role of the electron transport system in terms of the chemiosmotic hypothesis of Peter Mitchell.
  • Describe the preparation of amino acids, produced from the hydrolysis of proteins, so that they can enter energy metabolism

  (3)Applications

  • Understand energy metabolism in terms of the life of cells, organ systems, and organisms.
  • Understand the role of molecular oxygen (O2) in energy metabolism.
  • Appreciate the relationship between structure and function in the mitochondrium.
  • Appreciate the outline of the evolution of energy metabolism and the balance between photosynthesis and cellular respiration  the carbon and oxygen cycles.

III. OVERVIEW

    (1)  Introduction: Recall that in the previous notes we  converted each pyruvic acid molecule from glycolysis to acetyl CoA plus  carbon dioxide, and now start with acetyl CoA inside the mitochondrium.

Before we begin the next phase we should review the unique structure/function relationships of the mitochondrium, often termed the "power house of the cell" and note the outer membrane, the space between the outer membrane and the much-folded inner membrane i.e. cristae, and the matrix areas of the inner membranes. In addition, recall that this organelle contains a single circular chromosome and the ability to carry-out transcription and translation including the presence of ribosomes.


 

   (2)  The Citric Acid Cycle - this cycle is a series of nine enzyme-catalyzed reactions that begins with the transfer of the acetyl group from acetyl CoA to oxaloacetic acid forming the six carbon citric acid molecule. Thus the name the Citric Acid Cycle, look at the structure of citric acid and you will see that it contains three carboxylic acid functional groups giving rise to the name TCA Cycle or tricarboxylic acid cycle, or you may use the term Krebs Cycle after Sir Hans Krebs who worked out much of the details of the cycle. It is correctly called a cycle because it begins and ends with oxaloacetic acid, a four carbon keto-acid with two carboxylic acid functional groups

. The cycle is a series of conversions, including four oxidation/reduction reactions using coenzymes, which produces two molecules of carbon dioxide from the acetyl group introduced at the beginning of the cycle. Three of the four oxidation/reduction steps use NAD as the coenzyme and the other uses the coenzyme FAD, which has a lower energy value than NAD. In addition, one step combines GDP with inorganic phosphate to produce a GTP molecule, which we can consider to be similar to ATP. Note the two entering carbons are now in the lowest energy form to which cells can take carbon, i.e. carbon dioxide, and the energy is conserved in reduced forms of the coenzymes.


 

   (3) The Respiratory Electron Transport System - The reduced forms of NAD and FAD now begin a series of oxidation/reduction reactions at successively lower energy levels, which finally ends in the reduction of oxygen to form a molecule of water. This electron transport system is contained within the inner membrane of the mitochondrium. The energy of this electron transport system is used to pump protons across the inner membrane from the matrix to the outer intermembrane space, thus producing a pH gradient with the matrix being basic.

This charge separation or electrical potential , with the matrix being negative, is then used in ATP synthesis driven by proton-motive force.

The ATP synthase is contained within the inner membrane such that a flow of protons powers the combination of ADP and inorganic phosphate to ATP. Note that this inner membrane is impermeable to protons and they can only cross through the synthase complex.

This process of using electron flow down a energy gradient to create the energy of a proton gradient for ATP synthesis was formulated by Peter Mitchell in 1961 and termed the Chemiosmotic Theory. A key requirement of this process is the unique structure of the ATP synthase complex which spans the inner membrane and allows protons to enter from the outer intermembrane space and couple this electrochemical gradient energy to the combination of ADP and Pi into ATP production on the matrix side.

You may wonder how ADP and Pi formed in the cytosol when ATP is used can enter the mitochondrial matrix and how ATP formed in the matrix can leave and enter the cytosol?

  • The answer is that specific transport systems in the membrane make this possible. One is an adenine nucleotide translocase that is specific for ATP and ADP, and the other system promotes cotransport of inorganic phosphate from the outside with a proton into the matrix compartment and is the phosphate translocase that is specific for phosphate.

In addition, there are shuttle systems that oxidize extra-mitochondrial NADred and carry the reducing equivalents as carbon molecules into the mitochondria where the reduced form of NAD is then reformed.