Metabolism. Radioactive Isotopes

The manner in which the intricate chain of metabolic reactions could be worked out was greatly facilitated by the use of special varieties of atoms called "isotopes." During the first third of the twentieth century, physicists had discovered that most elements consisted of several such varieties. The body did not distinguish among them to any great degree but laboratory apparatus had been devised which could do so.

The German-American biochemist, Rudolf Schoenheimer (1898-1941), was the first to make large-scale use of isotopes in biochemical research. By 1935, a rare isotope of hydrogen, hydrogen-2, twice as heavy as ordinary hydrogen, was available in reasonable quantities. Schoenheimer used it to synthesize fat molecules that contained the rare hydrogen-2 ("heavy hydrogen" or "deuterium") in place of the ordinary hydrogen-i. These were incorporated into the diet of laboratory animals, whose tissues treated the heavy-hydrogen fat much as they would ordinary fat. Analysis of the body fat of the animals for hydrogen-2 content threw new and startling light on metabolism.

It was believed at the time that the fat stores of an organism were generally immobile, and were only mobilized in time of famine. However, when Schoenheimer fed rats on his hydrogen-2 fat, then analyzed the fat stores, he found that at the end of four days, the tissue fat contained nearly half the hydrogen-2 that had been fed the animal. In other words, ingested fat was stored and stored fat was used. There was a rapid turnover and the body constituents were undergoing constant change.

Schocnheimer went on to use nitrogen-15 ("heavy nitrogen") to tag amino acids. He would feed rats on a mixture of amino acids, only one of which might be tagged, and then find that after a short time, all the different amino acids in the rat were tagged. Here, too, there was constant action. Molecules were rapidly changing and shifting even though the over-all movement might be small.

In principle, one might follow the exact sequence of changes by detecting the various compounds in which the isotope appeared, one after the other. This was most easily done with radioactive isotopes, atom varieties which were unusual not only in weight but in the fact that they broke down, liberating fast-moving energetic particles. These particles were easily detected so that very small quantities of radioactive isotopes would suffice for experimentation. After World War II, radioactive isotopes were prepared in quantity by means of nuclear reactors. In addition, a radioactive isotope of carbon ("carbon-14") was discovered and found to be particularly useful.

Radioactive isotopes, for instance, enabled the American biochemist, Melvin Calvin (1911- ), to work out many of the fine details of the sequence of reactions involved in photosynthesis; that is, the manner in which green plants converted sunlight into chemical energy and supplied the animal world with food and oxygen.

Calvin allowed microscopic plant cells access to carbon dioxide in the light for only a few seconds, then killed the cells. Presumably only the first stages of the photosynthetic reaction chain would have an opportunity to be completed. The cells were mashed up and separated into their components by a technique called paper chromatography which will be described in the next chapter. Which of these components, however, represented the first stage of photosynthesis and which were present for other reasons?

Calvin could tell because the carbon dioxide to which the plant cells had had access contained radioactive carbon-14 in its molecules. Any substance formed from that carbon dioxide by photosynthesis would itself be radioactive and would be easily detected. This was the starting point of a series of researches through the 1950s that produced a useful scheme of the main steps in photosynthesis.