(Sciencedaily) - Wine, beer and yogurt are produced when microorganisms convert sugar into alcohol, gases or acids. But this process of fermentation--which is used by bacteria, fungi and other fast-growing cells to generate energy in the absence of oxygen--is a much less efficient way of generating energy for cells than aerobic respiration.

So why do many organisms use this seemingly wasteful strategy to generate energy instead of aerobic respiration, even when oxygen is readily available?

Biologists have pondered this conundrum for nearly a century and dubbed it the "Warburg effect" after the Nobel-Prize winning cell biologist Otto Warburg. He discovered in the 1920s that cancer cells generate energy by fermenting glucose, which generates a great deal of metabolic waste such as lactic acid.

Heavy usage of glucose by fermentation is, in fact, how tumors are identified in PET scans. But if this process is so inefficient, Warburg and others wondered, why do so many organisms depend on it instead of using the more efficient process of aerobic respiration?

A team of physicists and biologists from UC San Diego may have finally found the answer to this nearly 100-year-old mystery. In this week's issue of the journal Nature, the researchers examined the metabolic costs of synthesizing the enzymes and other biological apparatus required for fermentation and aerobic respiration within the bacterium E. coli as well as the metabolic savings of generating energy through aerobic respiration. They found that the cost of protein synthesis overrules the metabolic savings for fast growing cells.

"What we discovered could be compared to the difference between generating energy by a coal factory versus a nuclear power plant," said Terry Hwa, a professor of physics and biology at UC San Diego who headed the study. "Coal factories produce energy less efficiently than nuclear power plants on a per-carbon basis, but they are a lot cheaper to build. So the decision of which route to generate energy depends on the availability of coal and the available budget for building power plants."

"For cells, it turns out that there are also two costs to consider," he added. "One is the cost of raw material. Aerobic respiration generates more energy per carbon atom than fermentation. The other is the opportunity cost of synthesizing enzymes. This cost refers to the number of the protein-making machinery, or ribosomes, that need to be recruited to synthesize the relevant enzymes. We showed that the enzymes for respiration are bulky and slow compared to those for fermentation, so a lot of such enzymes need to be synthesized, tying up a lot of ribosomes, in order for respiration to happen at substantial rates. This is an important cost because the number of ribosomes is the growth limiting factor."

"For fast growing cells with plenty of nutrients, if a lot of ribosomes are used to make respiratory enzymes, then few of them are available to make other growth proteins, including the ribosomes themselves. This would slow down growth and is disadvantageous to cells. The higher carbon efficiency of respiration is not an important consideration here since nutrients are plentiful. On the other hand, when nutrients are scarce and cells cannot grow fast, then the demand for ribosomes by other cellular functions is reduced, and the cost of tying up ribosomes is less important. In the meantime, using respiration to generate energy conserves the precious carbon supplies, which is a much more important consideration in poor nutrient conditions."