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One of the observations Dr SubbaRow made while testing the phosphorus method seemed to provide a clue to the mystery what happens to blood sugar when insulin is administered. Biochemists began investigating the problem when Frederick Banting showed that injections of insulin, the pancreatic hormone, keeps blood sugar under control and keeps diabetics alive.

The mysterious colour delaying substance was a compound of phosphoric acid and creatine and was named Phosphocreatine. It accounted for two-thirds of the phosphorus in the resting muscle. When they put muscle to work by electric stimulation, the Phosphocreatine level fell and the inorganic phosphorus level rose correspondingly. It completely disappeared when they cut off the blood supply and drove the muscle to the point of "fatigue" by continued electric stimulation. And, presto! It reappeared when the fatigued muscle was allowed a period of rest.

 

Phosphocreatine created a stir among the scientists present when Fiske unveiled it before the American Society of Biological Chemists at Rochester in April 1927. The Journal of American Medical Association hailed the discovery in an editorial. The Rockefeller Foundation awarded a fellowship that helped SubbaRow to live comfortably for the first time since his arrival in the United States. All of Harvard Medical School was caught up with an enthusiasm that would be a life‑time memory for con�temporary students. The students were in awe of the medium-sized, slightly stoop shouldered, "coloured" man regarded as one of the School's top research workers.

 

SubbaRow's carefully conducted series of experiments disproved Meyerhof's assumptions about the glycogen-lactic acid cycle. His calculations fully accounted for the heat output during muscle contraction. Hill had not been able to fully account for this in terms of Meyerhof's theory. Clearly the Nobel Committee was in haste in  awarding the 1922 physiology prize, b�ut the biochemistry orthodoxy led by Meyerhof and Hill themselves was not too eager to give up their belief in glycogen as the prime source of muscular energy.

 

Fiske and SubbaRow were fully upheld and the Meyerhof-Hill� theory finally rejected in 1930 when a Danish physiologist showed that muscles can work to exhaustion without the aid of glycogen or the stimulation of lactic acid.

 

Fiske and SubbaRow had meanwhile followed a substance that was formed by the combination of phosphorus, liberated from Phosphocreatine, with an unidentified compound in muscle. SubbaRow isolated it and identified it as a chemical in which adenylic acid was linked to two extra molecules of phosphoric acid. By the time he completed the work to the satisfaction of Fiske, it was August 1929 when Harvard Medical School played host to the 13th International Physiological Congress. ATP was presented to the gathered scientists before the Congress ended. To the dismay of Fiske and SubbaRow, a few days later arrived in Boston a German science journal, published 16 days before the Congress opened.  It carried a letter from Karl Lohmann of Meyerhof's laboratory, saying he had isolated from muscle a compound of adenylic acid linked to two molecules of phosphoric acid!

 

While Archibald Hill never adjusted himself to the idea that the basis of his Nobel Prize work had been demolished, Otto Meyerhof and his associates had seen the importance of Phosphocreatine discovery and plunged themselves into follow-up studies in competition with Fiske and SubbaRow. Two associates of Hill had in fact stumbled upon Phosphocreatine about the same time as Fiske and SubbaRow but their loyalty to Meyerhof-Hill theory acted as blinkers and their hasty and premature publications reveal their confusion about both the nature and significance of Phosphocreatine.

 

The discovery of ATP and its significance helped reveal the full story of muscular contraction: Glycogen arriving in muscle gets converted into lactic acid which is siphoned off to liver for re-synthesis of glycogen. This cycle yields three molecules of ATP and is important in delivering usable food energy to the muscle. Glycolysis or break up of glycogen is relatively slow in getting started and in any case muscle can retain ATP only in small quantities. In the interval between the begin�ning of muscle activity and the arrival of fresh ATP from glycolysis, �Phosphocreatine maintains ATP supply by re-synthesizing it as fast as its energy terminals are used up by muscle for its activity.

 

Muscular contraction made possible by ATP helps us not only to move our limbs and lift weights but keeps us alive. The heart is after all a muscle pouch and millions of muscle cells embedded in the walls of arteries keep the life‑sustaining blood pumped by the heart coursing through body organs.  ATP even helps get new life started by powering the sperm's motion toward the egg as well as the spectacular transformation of the fertilized egg in the womb.

 

Archibald Hill for long denied any role for ATP in muscle contraction, saying ATP has not been shown to break down in the intact muscle. This objection was also met in 1962 when University of Pennsylvania scientists showed that muscles can contract and relax normally even when glycogen and Phosphocreatine are kept under check with an inhibitor. 

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