TY - JOUR
T1 - Regulatory principles in metabolism:Then and now
AU - Curi, Rui
AU - Newsholme, Philip
AU - Marzuca-Nassr, Gabriel Nasri
AU - Takahashi, Hilton Kenji
AU - Hirabara, Sandro Massao
AU - Cruzat, Vinicius
AU - Krause, Mauricio
AU - De Bittencourt, Paulo Ivo Homem
PY - 2016/1/1
Y1 - 2016/1/1
N2 - The importance of metabolic pathways for life and the nature of participating reactions have challenged physiologists and biochemists for over a hundred years. Eric Arthur Newsholme contributed many original hypotheses and concepts to the field of metabolic regulation, demonstrating that metabolic pathways have a fundamental thermodynamic structure and that near identical regulatory mechanisms exist in multiple species across the animal kingdom. His work at Oxford University from the 1970s to 1990s was groundbreaking and led to better understanding of development and demise across the lifespan as well as the basis of metabolic disruption responsible for the development of obesity, diabetes and many other conditions. In the present review we describe some of the original work of Eric Newsholme, its relevance to metabolic homoeostasis and disease and application to present state-of-The-Art studies, which generate substantial amounts of data that are extremely difficult to interpret without a fundamental understanding of regulatory principles. Eric's work is a classical example of how one can unravel very complex problems by considering regulation from a cell, tissue and whole body perspective, thus bringing together metabolic biochemistry, physiology and pathophysiology, opening new avenues that now drive discovery decades thereafter.
AB - The importance of metabolic pathways for life and the nature of participating reactions have challenged physiologists and biochemists for over a hundred years. Eric Arthur Newsholme contributed many original hypotheses and concepts to the field of metabolic regulation, demonstrating that metabolic pathways have a fundamental thermodynamic structure and that near identical regulatory mechanisms exist in multiple species across the animal kingdom. His work at Oxford University from the 1970s to 1990s was groundbreaking and led to better understanding of development and demise across the lifespan as well as the basis of metabolic disruption responsible for the development of obesity, diabetes and many other conditions. In the present review we describe some of the original work of Eric Newsholme, its relevance to metabolic homoeostasis and disease and application to present state-of-The-Art studies, which generate substantial amounts of data that are extremely difficult to interpret without a fundamental understanding of regulatory principles. Eric's work is a classical example of how one can unravel very complex problems by considering regulation from a cell, tissue and whole body perspective, thus bringing together metabolic biochemistry, physiology and pathophysiology, opening new avenues that now drive discovery decades thereafter.
KW - Flux control
KW - Futile cycles
KW - Metabolic pathways
KW - Substrate cycles
UR - http://www.scopus.com/inward/record.url?scp=85009414475&partnerID=8YFLogxK
UR - https://doi.org/10.25905/21555246.v1
U2 - 10.1042/BCJ20160103
DO - 10.1042/BCJ20160103
M3 - Review article
C2 - 27354561
AN - SCOPUS:85009414475
SN - 0264-6021
VL - 473
SP - 1845
EP - 1857
JO - Biochemical Journal
JF - Biochemical Journal
IS - 13
ER -