BMJ No 7115 Volume 315
News Saturday 25 October 1997
Nobel prize winners unravel aging process
| Dr John Walker from Britain and Dr Paul Boyer from the United States have been jointly awarded half of the Nobel prize for chemistry for their work in unravelling the mechanism by which adenosine triphosphate (ATP) - otherwise known as the universal currency of energy - is formed.
The mapping out of this complex process, together with a better grasp of the role of mitochondrial DNA in the disruption of ATP synthesis, may lead to a clearer understanding of aging and a range of nervous system diseases. |  |  |
| Dr John Walker has made a detailed study of adenosine triphosphate |
"Without ATP there wouldn't be life," said Dr Walker, senior scientist at the Medical Research Council's laboratory of molecular biology in Cambridge. And understanding how it is generated is "a piece of fundamental biology."
Dr Walker's work has focused on the structure of the enzyme ATP synthase, which forms ATP from adenosine diphosphate (ADP) and phosphate. He has used crystallog-raphy to clarify the three dimensional structure of ATP synthase and has so far established the structure of part of the enzyme known as F1, which contains the enzyme's catalytic sites.
He has also confirmed the mechanism by which ATP is made, which Dr Boyer, professor emeritus at the University of California, first proposed around 1980. This shows that energy released when sugar and fat are oxidised in the bloodstream powers up the electron transport chain which pumps protons out of the mitochondria. As the protons flow back into the mitochondria the current that they generate fuels the formation of ATP. A long * helix that passes through the centre of F1 is thought to rotate, allowing the capture of ADP and phosphate and then the release of the newly made ATP.
Dr Walker is also investigating the role of the mitochondrial DNA. This small molecule produces some of the proteins used to form the electron transport chain and ATP synthase - two essential components of ATP production. The DNA within mitochondria is more prone to damage by oxygen radicals than DNA contained in the cell's nucleus, explained Dr Walker. This mutation of DNA leads to faulty proteins. In turn the electron transport system and ATP synthase are disrupted and ATP production is less efficient. "This seems to be an important component of aging," said Dr Walker. "It has been shown that in mitochondria in the substantia nigra region of the brain in people with Parkinson's disease the DNA have mutated - this means that this area of the brain was unable to produce ATP."
Evidence is also accumulating that problems with energy production may lead to Alzheimer's disease. "In the long term, knowledge of how the effects of aging can affect the energy converting process could have medical implications," said Dr Walker.
The other half of the Nobel prize for chemistry was awarded to Dr Jens Skou from Aarhus University in Denmark, who was the first to show that enzymes can promote the transport of substances through a cell membrane.
Zosia Kmietowicz
London
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