Cell Respiration
We know that all cells must do work to stay alive and maintain their cellular environment. Cells obtain the energy to do work by oxidizing organic molecules, a process called cellular respiration that produces ATP. Although many organic molecules can be oxidized, glucose, the main product of photosynthesis, is the primary fuel molecule for the cells of living organisms.

All living organisms, both autotrophs and heterotrophs, must do cell respiration. In fact, the metabolic pathways used in the process of cellular respiration are the same in virtually all eukaryotic organisms. Recall that organisms that do photosynthesis (or properly, manufacture their own fuel molecules) are called autotrophs. Heterotrophs obtain their fuel molecules "pre-formed" by other organisms. Animals, fungi and many protists are heterotrophs, as are many bacteria. Plants and some protists are autotrophs, as are some bacteria.

Most eukaryotic organisms are aerobic (oxygen requiring). Cell respiration involves a series of oxidations of a fuel molecule, usually glucose. We will focus on the metabolism of glucose in this chapter. For a complete glucose metabolism, which is needed to sustain life for most organisms, glucose is broken down into water and carbon dioxide. This process requires oxygen.

C6H12O6 + 6O2 ( 6H2O + 6CO2 + 686kcal (ATP + Heat)

It should be noted that the metabolic pathways of cell respiration are variable, depending on the type of organism, the enzymes the organism has, and what the last molecule in the cell respiration process is. In aerobic cellular respiration, which is the complete metabolism of glucose, the final electron acceptor is oxygen, hence, the emphasis on oxygen in cell respiration. Most organisms are obligate aerobic organisms. They can not survive without the oxygen needed for aerobic cell respiration.

Not all cell respiration is aerobic. Fuel molecules can be oxidized without oxygen to yield smaller amounts of ATP. The fermentations involve the partial breakdown of glucose without using oxygen. Many prokaryotes have a variety of fermentation pathways, using a number of different fuel molecules. By definition, the end product for the fermentations is an organic molecule.

Organisms that do cell respiration without oxygen are said to be anaerobic. All organisms do some type of anaerobic respiration during times of oxygen deficit, although it may not be sufficient to sustain the organism's ATP needs.

Some organisms are obligate anaerobes. They cannot survive in the presence of oxygen. Other anaerobes are metabolic anaerobes; they lack the enzymes needed to do aerobic cell respiration. Some organisms will survive nicely in the absence of oxygen but will do aerobic respiration when oxygen is available.

Oxidation-Reduction Reactions in Cell Respiration
The oxidations of fuel molecules in cell respiration use specialized electron carrier molecules located in the membranes of the mitochondria. These electron transport molecules gain and lose electrons at specific energy levels. This is very similar to the electron transport molecules used in photosynthesis, discussed previously.

One of the most important of the electron transport molecules in cell respiration is NAD+. Electrons are passed through an electron transport chain to form ATP by chemiosmosis, a process sometimes called oxidative phosphorylation (or electron transport phosphorylation).

Not all of the ATP produced during cell respiration is by chemiosmosis. Some ATP is also synthesized by a direct transfer of phosphate from a substrate molecule to ADP. This process is called substrate-level phosphorylation. We will discuss this more when we do the details of the cell respiration pathways.

Let’s now turn to the details of Cellular Respiration.

Cell Respiration - An Overview
As with many metabolic processes, cell respiration has a number of stages.

Glycolysis
The initial stage of glucose metabolism, or cell respiration, is a process called glycolysis, which splits a glucose molecule into two molecules of pyruvate, a 3-carbon compound. Glycolysis occurs in the cytosol of the cell.

What follows glycolysis depends on the presence or absence of oxygen and/or the enzymes needed.

If oxygen is not available, or if the organism lacks enzymes needed for aerobic respiration, the pyruvate molecules will proceed with fermentations.

If oxygen is available and the organism has the enzymes to do aerobic respiration, the pyruvate molecules will be oxidized in the next stages of aerobic respiration.

The reactions of aerobic respiration after glycolysis occur in the mitochondria and are divided into the reactions that occur in the mitochondrial matrix and the electron transport reactions that occur in the inner mitochondrial membrane.

The Mitochondrial Matrix Stages


The Inner Mitochondrial Membrane Stage
The final stage of aerobic respiration is the electron transport chain and the chemiosmotic synthesis of ATP. Since the energy to synthesize ATP is from the oxidation-reduction reactions, the ATP formation is called oxidative phosphorylation.
Cellular Respiration - The Pathways
Glycolysis - Overview

Glycolysis Specifics
Glucose + 2ATP + 2NAD+ + 2ADP + 2P ----> 2 Pyruvate + 2NADH + 4ATP*
* Net gain of 2ATP

Summary of Glycolysis
Glucose + 2ATP + 2NAD+ + 2ADP + 2P --> 2 Pyruvate + 2NADH + 4ATP*
* Net gain of 2ATP
Inputs
  • Glucose
  • 2 ATP*
  • (And 2 NAD+ + 2 ADP + 2 P)
    Outputs
  • 2 Pyruvic acid
  • 2 NADH
  • 4 ATP* * Therefore the net energy yield is 2 ATP

    Note 1
    • The ATP generated is by substrate-level phosphorylation
    Note 2:
    • All steps are enzyme mediated
    • Glycolysis occurs in the cytoplasm of the cell
    • Glycolysis is the initial cell respiratory pathway of all eukaryotic organisms.


    After Glycolysis – Absence of Oxygen
    The Fermentations
    When no oxygen is available for aerobic cell respiration, eukaryotic organisms, and some prokaryotes, will complete glucose metabolism with the fermentation reactions.

    For some microorganisms, fermentation is a way of life. Some lack the enzymes to do the Krebs cycle; for others, oxygen is toxic. These are the strict (or obligate) anaerobes. Others, such as yeasts and E. coli are facultative organisms. When oxygen is available, they do aerobic respiration. When oxygen is not, they perform a fermentation.

    NADH carries very high energy electrons, but those electrons can be used to make ATP only in the presence of oxygen. In the fermentations the NADH electrons produced in glycolysis will be used to reduce Pyruvate to some other organic molecule, which becomes the final electron acceptor. This is needed to recover NAD+ for more glycolysis; no more ATP energy is obtained in the fermentation processes beyond the two ATP produced during glycolysis.

    In the Fermentations:
     Details of the Fermentations
    Lactic Acid Fermentation

    NADH -----> NAD+
    Pyruvate ----------------> Lactic Acid


    Alcoholic Fermentation

    NADH -----> NAD+
    Pyruvate --->Acetaldehyde ---------------> Ethanol (Ethyl Alcoholl) and ---> CO2



    Anaerobic Electron Transport (Those versatile Prokaryotes)
    A few bacteria do have an electron transport system. In those bacterial, some inorganic substance, such as Sulfur or Nitrogen molecules, becomes the final electron acceptor, rather than oxygen. Again, the process occurs to free NAD+, not to produce more ATP.

    Now let's turn to what happens after Glycolysis when oxygen is available -Aerobic Cellular Respiration

    Aeerobic Cellular Respiration     is comprised of two stages following Glycolysis, both of which occur in the mitochondria of the cell: the reactions in the mitochondrial matrix and the electron transport chain in the inner mitochondrial membrane.

    Matrix Reactions

    Inner Membrane Reactions
    Oxidation of Pyruvate to Form Acetyl


    For one glucose molecule (two pyruvate molecules), we will obtain:


    Note: When the level of ATP is high in a cell, the cell can convert acetyl-CoA into lipid molecules that can be stored for later energy use. This is one way that excess calories, no matter the nutrient source, are converted to fat.

    The Krebs Cycle (Citric Acid Cycle)
    The Krebs cycle is a means to remove energy rich H+ (with its electrons) (originally part of the glucose molecule) that can subsequently be used to generate ATP in electron transport via chemiosmosis.

    Essentially, the acids of the Krebs cycle are substances, which in the right conditions (i.e., The Krebs Cycle), can be oxidized (That is donate H+ with its electrons).

    For each glucose molecule, two ATP are produced in the Krebs cycle by substrate-level phosphorylation, one for each acetyl Co-A molecule that enters the Krebs cycle. (Recall that the glucose molecule has already gone through glycolysis and been converted to two molecules of Pyruvate in the cytoplasm prior to starting the Krebs cycle.)

    A closer Look at the Krebs (Citric Acid) Cycle
    Any cycle requires a substance to start the cycle (which will also be the end of the cycle). For the Krebs cycle the starter is Oxaloacetic acid (A 4-carbon acid), which is regenerated at the end of the cycle.

    The enzymes needed to do the Krebs cycle are located in the mitochondrial matrix.

    Acetyl-CoA combines with Oxaloacetic acid to begin the cycle.

    For each turn of the Krebs cycle we will get

    The Krebs Cycle - Specifics


    The Krebs cycle will turn two times for each glucose molecule doing aerobic cellular respiration, since glycolysis produces two Pyruvate. Therefore, for each glucose molecule that we start with, the Krebs cycle in its two turns (including the preparation step of pyruvate ( acetyl will produce:


    Electron Transport Systems
    The enzymes, proteins and electron carriers needed to do electron transport are found in the inner membranes of the mitochondria. ATP is produced by chemiosmosis using H+ concentration and electrical gradients to run the ATP Synthesis pumps in these membranes, as electrons are passed along the electron transport molecules in a series of oxidations and reductions.

    As the electrons are passed from one carrier to the next, the energy released is used to move H+ ions through the inner membrane into the intermembrane space of the mitochondrion. As the H+ concentration builds, it provides a H+ gradient that passes through a protein channel pore in the membrane that works with ATP synthase to generate ATP in the mitochondrial matrix.

    The Electron carriers, FADH2 and NADH, produced in the Krebs cycle (and in glycolysis), provide the electrons and Hydrogen needed to do the ATP synthesis.

    Oxygen is required as the final electron (and Hydrogen) acceptor, producing water as the end product of aerobic cellular respiration as the H+ and e- passed off the carriers combine with oxygen. (Recall that CO2 is also a product of aerobic cellular respiration.)

    How much ATP do we get from oxidizing glucose in aerobic cellular respiration? Summary of ATP Production from the complete aerobic metabolism of one glucose molecule

    From Electron Transport phosphorylation: 

         6 NADH from Krebs X 3 ATP each =                    18  ATP
     2 NADH from Pyruvic acid to Acetyl X 3 ATP each =    6  ATP
     2 NADH from Glycolysis X 2 (3) ATP* each =               4  (6) ATP
     2 FADH2 from Krebs  X 2 ATP each =                   4  ATP
    From Direct ATP synthesis (Substrate phosphorylation) 
         2 ATP directly from Krebs                                       2 ATP
     2 ATP directly from glycolysis                                  2 ATP

     Maximum Total ATP from 1 glucose =                       36 (38). ATP
    * These NADH hydrogens and electrons are actively transported into the mitochondria, resulting in a net of about 2 ATP per molecule rather than the usual 3 ATP.

    Aerobic (Cellular) Respiration Summary
    The complete aerobic respiration of glucose requires the following:


    The overwhelming majority of living organisms must do aerobic cellular respiration to stay alive. Fermentations and other anaerobic pathways provide insufficient ATP to sustain life for most organisms.


    Versatility of Metabolic Pathways
    Using other fuel molecules in the energy releasing pathways
    Some Notes