In the overlapping areas of protein and energy metabolism, French physiologist Jean-Baptiste Boussingault (1802-87), in 1844, performed a series of experiments using a cow fed only foods relatively low in protein (potatoes and beets) to prove that the manufacture of tissue protein did not require the incorporation of nitrogen from the air. A few years later, Carl von Voit and T. L. Bischoff (I860) in Germany confirmed that all the nitrogen in the body could come from the foods eaten and that the condition of nitrogen equilibrium or nitrogen balance could be established when the level of nitrogen intake was held constant. A major controversy developed during this period over the production of animal fat. Justus von Liebig maintained that the formation of fat from sugar was possible in the animal body, whereas other chemists, following the lead of Jean-Baptiste Dumas, maintained that fat in food was the only source of body fat. Boussingault, however, in 1845 proved conclusively that animals could produce fat from carbohydrates (McCollum 1957).
A series of studies that significantly linked protein and energy metabolism were those undertaken by Edward Smith in England in 1857.They demonstrated the effects of different conditions of life on the magnitude of energy requirements of human subjects. His major observation was that there was comparatively little change in the amount of urea (the major protein metabolite) voided during wide variations in the amount of labor performed, whereas the carbon dioxide produced increased in proportion to the amount of exercise. He devised a treadmill experiment with human subjects that provided strong evidence that the energy for muscular work could not have been derived from muscle degradation and almost conclusive evidence that the muscles were deriving energy from nonnitrogenous food. Unfortunately, the high authority of Liebig, who thought energy was derived from muscle degradation, prevented Smith’s studies from securing the attention they deserved.
In 1866, however, Adolf Fick and Johannes Wislicenus reported their famous mountain-climbing experiment of the previous year, using themselves as subjects, to confirm Smith’s tread-mill studies and also to put Liebig’s theory of muscular work to a crucial test. They abstained from protein food for some 17 hours before beginning the ascent of the Faulhorn, a peak in Switzerland with an altitude of 1,656 meters (5,433 feet). The climb to the summit required 6 hours, and during this time and for another 7 hours afterward, they consumed only carbohydrates and fats. Throughout they collected their urine, which was later analyzed for nitrogen content. During the 13-hour period, Fick produced 5 74 grams of urinary nitrogen and Wislicenus 5 54 grams. They reported:
We can assert from our own experience in the mountain ascent, that in spite of the amount of work and abstinence for 31 hours from albuminous food, neither of us felt the least exhausted. This could hardly have been the case if our muscular force had not been sustained by the non-nitrogenous food in which we partook. (McCollum 1957:126)
In the same year, E. Frankland (1866) pointed out that these results could be interpreted only by taking into account the amount of energy evolved in the combustion of a unit of muscle substance and by considering the work equivalent of this energy. In addition, he showed that the energy that the body derived from protein was equal to the difference between the total heat of combustion less the heat of combustion of urea, the major substance whereby the nitrogen in protein foods was eliminated. Frankland thus confirmed the conclusions already reached by Smith and by Fick and Wislicenus that muscles work at the expense of energy derived from the oxidation of the nonnitrogenous fats and carbohydrates (McCollum 1957).
The development of the concepts of intermediary metabolism of foodstuffs - that is, the step-by-step conversion of materials to the ultimate products, water and carbon dioxide (CO2), with the liberation of energy - was a slow intellectual process and had to await the accretion of knowledge of organic chemistry and, above all, the realization of the catalytic nature of the enzymes and their infinite variety (Levine 1978).
World History
