When we hear the word glycolytic pathway the first thought that comes to any biologist is the involvement of ribose sugar and ATP, NADP providing the energy for the breakdown of the glucose which in turn produces more ATP, NAD. But this was not the thing until 1900, the breakthrough researches have gave this metabolic pathways a big picture in the field of biochemistry. In this blog, we are going to discuss the discovery of the key players of the metabolic glycolytic pathway by Otto Meyerhof and Karl Lohmann.
Before the discovery of glycolytic pathway
The process of knowing glycolytic pathway in which glucose is converted into pyruvate and ATP began in the year 1860 when Louis Pasteur observed that microorganisms were responsible for fermentation. It took many years after this pioneer discovery to discover that the cell-free extracts could carry out fermentation by Eduard Buchner in 1897. Though the scientist knew that the ribose sugar was undergoing fermentation it took another few years to realise that inorganic phosphate was necessary for glycolysis and also that fermentation requires the presence of both a heat-labile component called “zymase” (contains a number of enzymes),heat-stable fraction called “cozymase.” (consists of metal ions, ATP, ADP, and coenzymes such as NAD. Science greatest discoveries always start with small initial observations, the discovery of the complete glycolytic pathway similarly was elucidated by 1940 with the help of these initial observations by the combined efforts of several scientists.
Otto Meyerhof’s journey to discover energetics of living cells
Otto Meyerhof’s journey of bioenergetics discovery started around 1909 when he was appointed in a laboratory by, Ludolfvon Krehl in a small research program on metabolism at the University of Heidelberg Medical Clinic in Germany.
Since ancient ages after the discovery of food people knew that in order to do our day to day life work we need to consume food for fulfilling energy requirement. Though people knew the basic of food requirement but the mechanism which converts food into energy was not known. Meyerhof with the help of different experiments recognized that after energy is input as food it is transformed through a series of intermediate steps and finally dissipated as heat. Later on, he gave one of the first adaptations of the physical laws of thermodynamics to physiological chemistry and applied it on the energetics of living cells.
He soon began using muscle to look at energy transformations and chemical changes during cellular function. Meyerhof was also interested in analogies between oxygen respiration in muscle and alcoholic fermentation in yeast and later on in 1918, he proved that the coenzymes involved in lactic acid production were the same as the yeast coenzymes discovered by Harden and Young which helped in revealing an underlying unity in biochemistry.
How Meyerhof deciphered cyclical nature of metabolism?
While Meyerhof was working with Archibald Vivian Hill and when they were investing the heat production in muscle, Meyerhof found that the presence or absence of oxygen had a direct impact on the amount of glycogen consumed. He determined that glycogen is converted to lactic acid in the absence of oxygen and showed that in the presence of oxygen only a small portion of lactic acid is oxidized and the rest is converted back to glycogen. This discovery of the lactic acid cycle provided the first evidence of the cyclical nature of energy transformation in cells. These results also confirmed and extended Louis Pasteur’s theory (now called the Pasteur-Meyerhof effect) that less glycogen is consumed in muscle metabolism in the presence of oxygen than in its absence. This was the beginning of metabolism involving various cycles in terms of heat development, mechanical work, and cellular chemical reactions.
The involvement of ATP by Meyerhof and Karl Lohmann.
The discovery of ATP was first reported by Lohmann in 1929. Karl Lohmann was an assistant in Otto Meyerhof’s laboratory. The beginning of ATP discovery started when Gustav Embden discovered adenylic acid (AMP) in muscle. With the help is this Lohmann isolated inorganic pyrophosphate (PP) by hydrolysing phosphates from the adenylic acid (AMP) by heating it for 7 minutes in 1 N HC1 at 100*C in 1928 and later on it became apparent that, giving an alkaline reaction during the isolation of Embden’s AMP and also of Lohmann’s PP, resulted in the splitting of ATP to AMP and PP. Thus the most important organic compound ATP was discovered.
Soon Meyerhof determined the splitting of ATP and the uptake of phosphate during the breakdown of carbohydrates to lactic acid. By 1934, Kurt Lohmann in Meyerhof’s laboratory provided direct evidence that ATP synthesis was the byproduct of the utilization of glucose. Lohmann also established that creatine phosphate is an energy source for ATP phosphorylation, which led Meyerhof to the conclusion that the energy released from ATP hydrolysis was the primary event leading to muscle contraction.
By the 1930s Meyerhof managed to isolate and purify the co-enzymes involved in the conversion of glycogen to lactic acid and also reconstructed the main steps of this set of reactions in cell-free solution. Meyerhof’s group discovered more than one-third of the enzymes involved in glycolysis. In 1932, Gustav Embden constructed a detailed proposal for reaction sequences for almost the entire glycolytic pathway. Over the next 5 years, Meyerhof, along with Warburg, Jacob Parnas, Carl Neuberg, Gerti and Karl Cori, and Hans von Euler worked out the details of glycolysis, which is often referred to as the EmbdenMeyerhof pathway.