The Nobel Prize in Chemistry 1997

The Royal Swedish Academy of Sciences has awarded the 1997 Nobel Prize in Chemistry with one half to Paul D. Boyer and John E. Walker for their elucidation of the enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP); and with one half to Jens C. Skou, for the first discovery of an ion-transporting enzyme, Na⁺, K⁺-ATPase.

Paul D. Boyer University of California Los Angeles, U S A	John E. Walker Medical Research Council Laboratory of Molecular Biology Cambridge, United Kingdom	Jens C. Skou Aarhus University Denmark

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Life’s energy currency, ATP

All living organisms, from bacteria, fungi, spinach and worms to crocodiles and humans, use ATP for energy conversion.

Originally, the energy comes from the sun.

Plants capture it during photosynthesis and convert it to chemical energy as ATP. Using this energy, plants produce carbohydrates, fats and proteins which are eaten by animals and human beings.

In metabolism, the food is broken down and the energy released is used to make ATP.

Energy is interconverted between various forms. Compare this with the idea of different currencies, only one of which is accepted at a time. ATP is an energy currency.

 The universal energy transporter

 Adenosine triphosphate (ATP) is built up of adenosine and three phosphate groups. The removal of the terminal phosphate group from ATP produces adenosine diphosphate (ADP).

Every day an adult converts a quantity of ATP corresponding to at least half his or her body weight, and nearly a ton during a day of hard work.

Paul D. Boyer and John E. Walker have shown how the enzyme ATP synthase makes ATP. ATP synthase is found in chloroplast and mitochondrial membranes and in the cytoplasmic membrane of bacteria. A difference in hydrogen ion concentration across the membrane drives the enzyme to synthesise ATP.

“The Binding Change Mechanism”

Using chemical methods Paul Boyer proposed that ATP synthase is like a cylinder with alternating alpha and beta subunits. An asymmetrical gamma subunit in the middle of the cylinder causes changes in the structure of the beta subunits when it rotates (100 r.p.s.). He termed these structures open (beta_O), loose (beta_L) and tight (beta_T).

Four stages in ATP synthesis                                                                        

A molecular machine is discovered

John Walker crystallised the enzyme to study its details. He established that Boyer’s proposal for how ATP synthesis takes place, the “molecular machine”, was correct.

 ATP synthase

The enzyme consists of an F_O part bound in the membrane and a projecting F₁ part. The F₁ part is known in detail, while less is known about the F_O part.

The F_O part consists of three different protein molecules (subunits a, b and c). When hydrogen ions flow through the membrane via a disc of c subunits, the disc is compelled to rotate. The gamma subunit in the F₁part is fixed to the disc and therefore rotates with it. The alpha and beta subunits in the F₁ part, however, cannot rotate because they are locked in a fixed position by the b subunit, which is anchored to subunit a in the membrane.

As the gamma subunit functions as an assymmetrical axle, the beta subunits are compelled to undergo the structural changes described in the figures above.

Jens C. Skou was the first to describe an ion pump – an enzyme that gives directed transport of ions through a cell membrane: a fundamental mechanism in every living cell. The existence of several similar ion pumps has since been demonstrated.

The first ion pump discovered  

Jens Skou discovered Na⁺, K⁺-ATPase – an enzyme that maintains the balance of sodium (Na⁺) and potassium (K⁺) ions in cells. Within cells, the concentration of Na⁺ ions is lower, and that of K⁺ ions higher, than in the surrounding fluid.

Na⁺, K⁺-ATPase and other ion pumps must work all the time in our body. If they were to stop, our cells would swell up, and might even burst, and we would rapidly lose consciousness. A great deal of energy is needed to drive ion pumps – in humans, about 1/3 of the ATP that the body produces.

Na⁺, K⁺-ATPase cycles between two states
– open to the inside or the outside of the cell  

 Ion pumps and pharmaceuticals

Ion pumps are affected by chemical substances. Digitalis plants contain a substance that inhibits Na⁺, K⁺-ATPase which results in an accumulation of sodium ions in cells. Used as a pharmaceutical, it causes reinforced heart muscle activity. Modern medicines against stomach ulcers suppress the activity of an ion pump that creates an acidic environment in the stomach.

資料來源：http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1997/illpres/index.html