Sunday, July 3, 2011

Glycolysis (general ideas) – part 1

The word glycolysis derives from the greek terms glykis (sweet) + lysis (lysis). Indeed, it means what happens on this metabolic pathway – glucose (that is a sugar with 6 carbon atoms) is cleaved into 2 pyruvate molecules (3 carbon atoms). It can be also called Embden-Meyerhoff pathway.
Glycolysis was the first metabolic pathway to be elucidated. It is the pathway that presents the highest flow of carbon atoms in the majority of our cells. Glycolysis is the first stage of carbohydrate catabolism, and is, under normal conditions, the unique source of metabolic energy in many tissues (brain, red blood cells, etc.). it is independent of the presence of oxygen, and, consequently, it can occur both in aerobic and anaerobic conditions. It is important to highlight that, in anaerobic conditions, glycolysis is the only source of energy in our body.

Short historical perspective
In 1897, two German investigators, Hans and Eduard Buchner, were interested in the production of yeast extracts without any cells, for therapeutic purposes. Thus, they mixed yeast with sand and macerated it.

Hans Buchner            Eduard Buchner

However, the conservation of the extracts was a potential problem – they could not use antiseptics, like phenol (because they wanted to use the extracts to feed animals), and the have decided to conserve the extracts with sucrose, a conserver widely used in culinary. This decision had a huge impact on biochemistry! They have obtained a “surprising” result (it is important to not forget that we are talking in the end of 19th century…): sucrose was rapidly fermented to alcohol by the yeast extract. This was the 1st demonstration that fermentation could ocorrer in the absence of living cells, which was in clear contrast with what had been postulated in 1860 by Louis Pasteur (he stated that fermentation was strictly associated to living cells, the basis of Vitalism!).
Some years later, in 1905, Arthur Harden and William Young demonstrated that fermentation started rapidly after addition of glucose to yeast extracts, but it stopped a after a few moments, unless it was added inorganic phosphate. Moreover, they reported that the extract loosed its activity when warmed up or dialyzed. Those observations are now easily understandable by the fact that the heat interferes with the glycolytic enzymes and the dialysis led to a dilution of small molecules and ions. In that time, the heating-sensible component was called zymase, and the one dialysis-sensible was called cozymase.

Arthur Harden                      William Young

Glycolysis was fully elucidated around 1940, due to the contributions of many investigators, namely: Gustav Embden, Otto Meyerhoff (discovered hexokinase and aldolase), Carl Neuberg (has made the first utilization of metabolic inhibitors on glycolysis in particular and in Biochemistry in general!), Jacob Parnas, Otto Warburg, Gerty Cori and Carl Cori.

Main bibliographic sources:
- Quintas A, Freire AP, Halpern MJ, Bioquímica - Organização Molecular da Vida, Lidel
- Nelson DL, Cox MM, Lehninger - Principles of Biochemistry, WH Freeman Publishers

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