Tuesday, October 2, 2012

Misconceptions in Metabolism II

Originally Posted on  by hsauro

A week ago I wrote about some misconceptions in metabolism that arose from a trip to a systems biology workshop in Holland. This week I discovered that Nature is perpetrating similar misconceptions in their News and Views section.

I came across the News and Views article: “Cancer Metabolism: When more is less” by Lei Jiang & Ralph J. DeBerardinis. They review a recent paper in Nature Chemical Biology by Anastasiou et al. which showed that increases in Pyruvate Kinase levels may depress metabolites concentrations upstream of the enzyme step. Not a surprising conclusion if one understands basic enzyme kinetics. The original paper was ok though it seemed to over emphasize the structural aspects of the story compared to the system implications which were perhaps more interesting.

The News and Views article however went rogue on us, and perpetrated in fine form the misleading notion of bottlenecks in metabolic pathways, something I thought had been laid to rest 40 years ago with the publication of the seminal works by Kacser and Burns and Heinrich and Rapoport. The term bottleneck is a very imprecise word to use for something which is actually far more subtle. What really annoyed me was Nature’s use of the figure shown below. The figure is nicely drawn but it overly simplifies a much more complex situation. More dangerous however is it gives the impression that metabolism can be regulated at single steps which in general is quite wrong. Nature has done a great disservice to the scientific community with this article. Molecular Biologists have enough difficulties most of the time understanding complex systems without giving them tempting simplistic stories and pretty pictures. Being published Nature unfortunately gives the story an unwarranted air of authority which it does not deserve.