Overflow Metabolism: From Yeast to Marathon Runners

By Alexei Vazquez

Overflow Metabolism: From Yeast to Marathon Runners provides an overview of overflow metabolism, reviewing the major phenomenological aspects as observed in different organisms, followed by a critical analysis of proposed theories to explain overflow metabolism. In our ideal view of metabolism, we think of catabolism and anabolism. In catabolism nutrients break down to carbon dioxide and water to generate biochemical energy. In anabolism nutrients break down to generate building blocks for cell biosynthesis. Yet, when cells are pushed to high metabolic rates they exhibit incomplete catabolism of nutrients, with a lower energy yield and excretion of metabolic byproducts.

This phenomenon, characterized by the excretion of metabolic byproducts that could otherwise be used for catabolism or anabolism, is generally known as overflow metabolism. Overflow metabolism is a ubiquitous phenotype that has been conserved during evolution. Examples are the acetate switch in the bacterium E. coli, Crabtree effect in unicellular eukaryote yeasts, the lactate switch in sports medicine, and the Warburg effect in cancer. Several theories have been proposed to explain this seemingly wasteful phenotype. Yet, there is no consensus about what determines overflow metabolism and whether it offers any selective advantage.

• Includes examples of overflow metabolism and major phenomenological features
• Features a critical view of proposed theories to explain overflow metabolism
• Provides a summary of our preview work, proposing molecular crowding as the cause of overflow metabolism, together with new unpublished results

• Language: English
• Publisher: Academic Press
• Release date: Oct 16, 2017
• ISBN: 9780128123355

Alexei Vazquez

Alexei Vazquez began his studies in Physics at the University of Havana, where he obtained a BSc and MSc degrees in 1995 and 1997. In 2002 he obtained a PhD degree in Statistical and Biological Physics from the International School of Advanced Studies in Trieste. Subsequently, he held postdoctoral positions at the University of Notre Dame in Indiana and at the Institute for Advanced Study in Princeton. From 2009 to 2014, Dr. Vazquez was an Assistant Professor at The Cancer Institute of New Jersey. Since 2014 he is a group leader at the Cancer Research UK Beatson Institute in Glasgow. Dr.Vazquez research focuses on cancer metabolism, using theoretical and experimental methods.

Book preview

manuscript.

Chapter 1

A Historical View of Overflow Metabolism

Abstract

Metabolism is the biological process where cells, tissues or whole organisms utilize organic molecules for survival, proliferation and to transform the environment. Metabolism is conceptually divided into catabolism and anabolism. Catabolism involves the breakdown of organic molecules to generate energy and precursor molecules for anabolism. Anabolism involves the synthesis of cell components from precursor molecules and energy. When catabolism is fully efficient, organic molecules are fully incorporated into the cell biomass or they are broken down to carbon dioxide to obtain the maximum energy yield. Under certain conditions, the organic molecules are only partially broken, and the products of incomplete catabolism are released to the environment. This phenomenon of incomplete catabolism, characterized by the excretion of metabolic products that could be otherwise incorporated in the cell biomass or catabolized to carbon dioxide, is called overflow