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NCERT tells you that ATP is the energy currency of the cell, and that pyruvic acid joins coenzyme A to form acetyl CoA before entering the Krebs cycle. Both ideas owe a great deal to one biochemist, Fritz Lipmann. This post covers who he was, how he came to see phosphate bonds as a way of moving energy around the cell, how he found coenzyme A, a worked example from his own Nobel lecture, and what students can take from how he worked.
Who was Fritz Lipmann?
His Nobel Prize facts page records that he was born on 12 June 1899 in Koenigsberg, Germany (now Kaliningrad, Russia), and died on 24 July 1986 in Poughkeepsie, New York. He was at Harvard Medical School and Massachusetts General Hospital when he won half of the 1953 Nobel Prize in Physiology or Medicine "for his discovery of co-enzyme A and its importance for intermediary metabolism". The other half went to Hans Krebs, whose cycle we cover in our post on Krebs.
How did Lipmann think about cell energy?
In his Nobel lecture, Lipmann says he trained with Otto Meyerhof and then studied how a bacterium, Lactobacillus delbrueckii, oxidises pyruvic acid. He made an accidental observation: the oxidation depended completely on inorganic phosphate. Adding adenylic acid (AMP) made phosphate disappear, and it turned up as ATP. He concluded that the missing link in the reaction chain was acetyl phosphate.
At the time, he says, phosphorylation was thought to be tied specifically to glycolysis. His system coupled it to respiration. That suggested a much wider principle: energy from oxidation could be turned into "phosphate bond energy" and passed on to many building reactions. He proposed "the generalization of the phosphate bond as a versatile energy distributing system". He set this out in a long review in 1941, Metabolic generation and utilization of phosphate bond energy.
How did he find coenzyme A?
Lipmann next wanted to know whether acetyl phosphate was the "active acetate" that cells use to build molecules. To test it, the lecture explains, he chose a simple, sensitive reaction: the acetylation of an aromatic amine, sulfanilamide, by liver extracts. Pigeon liver turned out to have an exceedingly potent acetylation system. He reported it in the Journal of Biological Chemistry in 1945 as Acetylation of sulfanilamide by liver homogenates and extracts43110-9).
Acetyl phosphate turned out not to be the donor in pigeon liver. But the work revealed something else: a heat-stable factor that disappeared from enzyme extracts on ageing or dialysis, was present in boiled extracts of all organs, and could not be replaced by any known cofactor. With Nathan Kaplan, Lipmann showed it was a common factor in the acetylation of sulfanilamide and of choline41419-0) (1946). With help from Roger Williams's laboratory, Beverly Guirard found that acid hydrolysis released pantothenic acid, a B vitamin. The Nobel facts page says Lipmann discovered the substance in 1946 and gave it the name coenzyme A. In 1947 the group described it as a coenzyme for acetylation, a pantothenic acid derivative30973-0).
A worked example: checking the sulphur
The lecture reports that the purest coenzyme A preparation contained 4.13% sulphur, "corresponding to one mole per mole of pantothenate", and gives the calculated molecular weight as 767. Let us check that.
If one molecule (molar mass 767 g/mol) contains one sulphur atom (32.06 g/mol), the sulphur fraction is 32.06 / 767 = 0.0418, or 4.18%.
The measured 4.13% differs from 4.18% by only 0.05 percentage points, about 1% of the value, so one sulphur per molecule fits.
An earlier sample, the lecture says, was about 40% pure and contained about 2% sulphur. If only 40% of the sample is coenzyme A, expected sulphur = 0.40 × 4.18% = 1.67%, which rounds to about 2%.
The lecture says the sulphur was identified as a potential SH group, and that Feodor Lynen later identified acetyl CoA as the thioester of CoA: the acetyl group is attached through that sulphur.
Common mistakes:
Treating a percentage as a molecule count. Convert with molar masses; 4.13% is not "4 sulphur atoms".
Ignoring purity. An impure sample dilutes every element by the same factor.
Mixing up CoA and ATP. The lecture compares them: ATP carries phosphoryl groups, CoA carries acetyl groups. Both are carriers that move a group from donor to acceptor.
Where does coenzyme A appear in your syllabus?
The NCERT Class 11 chapter on respiration in plants states that ATP acts as the energy currency of the cell, and writes the link reaction as pyruvic acid + CoA + NAD+ → acetyl CoA + CO2 + NADH + H+. The acetyl group then condenses with oxaloacetic acid to start the citric acid cycle, and CoA is released. Lipmann's lecture describes this very step being shown to depend on CoA. Our guide to respiration in plants covers the full pathway.
What can a student take from Lipmann's way of working?
Chase the surprise. A switch of buffer showed that phosphate was essential, and that observation shaped his career.
Follow the thing that disappears. The factor that vanished on dialysis was the discovery.
Look for the general rule. He moved from one bacterial reaction to a principle about energy in all cells.
If chemistry like percentage composition still trips you up in biology questions, the Fermi Problem Library has worked problems with a step-by-step solver that explains the reasoning rather than printing an answer.
Try it now: write the link reaction from memory, then say where each of the three carbon atoms of pyruvic acid ends up.
