Nonlinear enzyme kinetics can lead to high metabolic flux control coefficients: implications for the evolution of dominance

Journal of Theoretical Biology
U GrossniklausV Nanjundiah

Abstract

In a classic study, Kacser & Burns (1981, Genetics 97, 639-666) demonstrated that given certain plausible assumptions, the flux in a metabolic pathway was more or less indifferent to the activity of any of the enzymes in the pathway taken singly. It was inferred from this that the observed dominance of most wild-type alleles with respect to loss-of-function mutations did not require an adaptive, meaning selectionist, explanation. Cornish-Bowden (1987, J. theor. Biol. 125, 333-338) showed that the Kacser-Burns inference was not valid when substrate concentrations were large relative to the relevant Michaelis constants. We find that in a randomly constructed functional pathway, even when substrate levels are small, one can except high values of control coefficient for metabolic flux in the presence of significant nonlinearities as exemplified by enzymes with Hill coefficients ranging from two to six, or by the existence of oscillatory loops. Under these conditions the flux can be quite sensitive to changes in enzyme activity as might be caused by inactivating one of the two alleles in a diploid. Therefore, the phenomenon of dominance cannot be a trivial "default" consequence of physiology but must be intimately linked to the mann...Continue Reading

Citations

Feb 24, 2001·Genome Biology·M C Wildermuth
Dec 8, 2004·Genetics·Homayoun C Bagheri, Günter P Wagner
Aug 16, 2015·Biology Direct·Reiner A Veitia, James A Birchler
Sep 15, 2005·Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution·Homayoun C Bagheri
Aug 14, 1999·Heredity·D Bourguet
Jun 3, 2019·Biological Reviews of the Cambridge Philosophical Society·Adam F JohnsonReiner A Veitia
Dec 17, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Reiner A Veitia
Aug 10, 2000·Journal of Theoretical Biology·L D Hurst, J P Randerson
Nov 28, 2002·Journal of Theoretical Biology·Reiner A Veitia
Jun 6, 2003·Mathematical Biosciences·Homayoun Bagheri-ChaichianGünter P Wagner
Aug 19, 2008·Journal of Theoretical Biology·Paul S Agutter

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Methods : a Companion to Methods in Enzymology
O Monasterio
Journal of Theoretical Biology
T Höfer, R Heinrich
Proceedings of the National Academy of Sciences of the United States of America
H A Orr
© 2021 Meta ULC. All rights reserved