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Wednesday, April 11, 2007

Nobel Laureate: Fritz Lipmann


The Nobel Prize in Physiology or Medicine 1953.

Fritz Albert Lipmann (1899-1986): "for his discovery of co-enzyme A and its importance for intermediary metabolism"

Fritz Lipmann won the Nobel Prize in 1953 for his discovery of the cofactor Coenzyme A (CoA). Initially Coenzyme A was found to be the cofactor that bound acetyl groups for oxidation by the citric acid cycle. (Also known as the Krebs cycle. Hans Krebs shared the Nobel Prize with Lipmann in 1953 [Hans Krebs].) Here's how Lipmann's discovery is described in the presentation speech.
It is necessary to introduce compounds from the outside into the Krebs cycle in order to keep it in operation, because theoretically speaking the integral components are not used up in the process. The principal incorporation takes place through Lipmann's 2-carbon compound. It had been generally assumed that this compound was closely related to acetic acid. It was known that large amounts of acetic acid are formed in the metabolism of the cell. This acid possesses two carbon atoms and could fit well into the mechanism of the Krebs cycle. It seemed quite certain that the 2-carbon compound was acetic acid, but that it was active in some unknown form. Lipmann maintained for several years that acetyl phosphate, a compound formed from acetic acid and phosphoric acid was the active principle and he defended this idea against a growing scepticism of his colleagues. Just when most biochemists became convinced that this compound would not fit into the mechanism of the Krebs cycle, and were ready to abandon the whole idea, Lipmann announced his discovery of coenzyme A. Now suddenly everything fitted perfectly - the last notch of a combination lock fell into its place.

Coenzyme A is a compound with a rather small molecule, which, when united with the enzyme-protein, acquires the property of binding acetic acid. Acetic acid is normally quite unreactive but when bound in this way it becomes labile and reactive and represents the previously mystical 2-carbon compound which combines with a 4-carbon compound to form citric acid. A new way for the transmission of energy in the cell was demonstrated by this discovery.
We now know that Coenzyme A plays a role in several other biochemical reactions, including one of the reactions of the citric acid cycle where succinyl-CoA is a key intermediate. It also plays a role in fatty acid synthesis (via malonyl-CoA) and in fatty acid degradation (via acetoacetyl-CoA).

Lipmann's name is associated with one of the most spectacular cases of scientific fraud. In the early 1960's a postdoctoral fellow in Lipmann's lab managed to fake a lot of data and he published several scientific papers with Lipmann. All of the data, including the notebooks, were elaborately constructed to look real. One of my colleagues, Byron Lane, (now retired) was given the unenviable task of uncovering the fraud when he was working in Lipmann's lab.

[Lipmann photo from the National Library of Medicine]

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