Transcribed TextTranscribed Text

Part I - What Are They? Paper #1: Mitchell, P. 1961. Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature 191:144-148. This paper hypothesizes the coupling of phosphorylation to electron transfer across a membrane. In the introduction to his paper, Mitchell acknowledged how different his approach to the problem of ATP synthesis was by calling the reductionist biochemical approach the "orthodox" approach at the time. He suggested that somehow the components involved in ATP synthesis needed to be spatially positioned within the membrane so that the individual elements would transfer electrons and protons (the elements of water: H* and OH~) across the membrane. What does spatial positioning mean? It means that the location of each component in relationship to the other compo- nents in the system is important if the system is to function. For example, a toy truck won't work if all of the pieces are scattered on a table. The truck only works when the pieces are assembled properly in space, as illustrated in Figure 3. Figure 3. A metaphor to highlight the importance of spatial positioning. A truck is more than just the sum of its parts. While it may not seem radical now, this concept was so contrary to the thinking at the time that Mitchell devoted much of his introduction to acknowledging that he was proposing a novel or unorthodox approach to the problem. He suggested a model in which the intermediates in the pathway for ATP synthesis needed to be positioned in space within a membrane, not just mixed all together in the cell cytoplasm. Mitchell presented theoretical calculations to show how a reversible ATPase system located in a membrane could separate charges on the outside and inside of the membrane. Based on his calculations, he came up with the diagram in Figure 4. Questions Inside (L) Membrane Outside (R) 1. Based on the diagram, is the overall charge outside the membrane positive or negative? ADP-0 OH' Pt POH 2. Based on the diagram, is the overall charge inside the 1. R' H+ membrane positive or negative? ADP-0-P+ 3. Which side of the membrane has a lower pH? 4. Which side of the membrane is more acidic? Figure 4. The original caption for this figure in Mitchell (1961) reads: "Fig. 1. Anisotropic reversible "ATPase' system located in an ion-impermeable membrane between aqueous phases L and R." Credit: Reprinted by permission from Macmillan Publishers Ltd: Nature ©1961. Mitchell knew that different metabolic inhibitors could inhibit oxidative phosphorylation, and he tentatively identi- fied some of the components in his hypothetical system (Figure 5). He hypothesized that a flavoprotein, a quinone, and a cytochrome were important in oxidative phosphorylation. He placed these macromolecules within or adjacent to his membrane, based on the knowledge at the time. Please note that the notation for some molecules was different in 1961. Inside (L) Membrane Outside ('R) SH, DPN* FP + H+ O+H S+H* OPNH FPH2 2H QH2 0+H+ 20 2e Cyt. Q+2H* OH` 3(ADP+P) 30H'< H+ 3ATP Figure 5. The original caption for this figure in Mitchell (1961) reads: "Fig. 3. Diagram of chemi-osmotic sys- tem for coupling phosphorylation to the oxidation of substrate (SH,) through DPN, FP (tentatively identified with flavoprotein), Q (tentatively identified with a quinone) and the cytochromes (Gyt.)." Credit: Reprinted by permission from Macmillan Publishers Ltd: Nature ©1961. Questions 5. Use Figure 5 above to complete the following: a. Identify the following components: flavoprotein, quinone, and cytochrome. b. Circle the protons. c. Draw boxes around the electrons. 6. In Figure 5 does a proton or an electron cross the membrane first? 7. Is the cytochrome translocating protons or electrons? 8. In Figure 5, how many ATPs are made via the spatially positioned system? 9. Do you know how many ATPs scientists currently think are made with the electron transport chain? Mitchell concluded his paper by stating: "The underlying thesis of the hypothesis put forward here is that if the process that we call metabolism and transport represent events in a sequence, not only can metabolism be the cause of transport, but also transport can be the cause of metabolism. Mitchell understood that his proposal was contrary to the conventional biochemical approach. It took several other experiments to move the scientific community towards accepting Mitchell's hypothesis.

Solution PreviewSolution Preview

These solutions may offer step-by-step problem-solving explanations or good writing examples that include modern styles of formatting and construction of bibliographies out of text citations and references. Students may use these solutions for personal skill-building and practice. Unethical use is strictly forbidden.

    By purchasing this solution you'll be able to access the following files:

    for this solution

    or FREE if you
    register a new account!

    PayPal, G Pay, ApplePay, Amazon Pay, and all major credit cards accepted.

    Find A Tutor

    View available Cellular Biology Tutors

    Get College Homework Help.

    Are you sure you don't want to upload any files?

    Fast tutor response requires as much info as possible.

    Upload a file
    Continue without uploading

    We couldn't find that subject.
    Please select the best match from the list below.

    We'll send you an email right away. If it's not in your inbox, check your spam folder.

    • 1
    • 2
    • 3
    Live Chats