An enzyme activation network provides evidence for extensive regulatory crosstalk between metabolic pathways

Author:

Al Zubaidi Sultana Mohammed,Nasar Muhammad IbtisamORCID,Ralser MarkusORCID,Notebaart Richard A.,Alam Mohammad TauqeerORCID

Abstract

AbstractEnzyme activation by cellular metabolites plays a pivotal role in regulating metabolic processes. Nevertheless, our comprehension of such activation events on a global network scale remains incomplete. In this study, we conducted a comprehensive investigation into the optimization of cell-intrinsic activation interactions withinSaccharomyces cerevisiae. To achieve this, we integrated a genome-scale metabolic model with enzyme kinetic data sourced from the BRENDA database. Our objective was to map the distribution of enzyme activators throughout the cellular network. Our findings indicate that virtually all biochemical pathways encompass enzyme activators, frequently originating from disparate pathways, thus revealing extensive regulatory crosstalk between metabolic pathways. Indeed, activators have short pathway lengths, indicating they are activated quickly upon nutrient shifts, and in most instances, these activators target key enzymatic reactions to facilitate downstream metabolic processes. Interestingly, non-essential enzymes exhibit a significantly higher degree of activation compared to their essential counterparts. This observation suggests that cells employ enzyme activators to finely regulate secondary metabolic pathways that are only required under specific conditions. Conversely, the activator metabolites themselves are more likely to be essential components, and their activation levels surpass those of non-essential activators. In summary, our study unveils the widespread importance of enzymatic activators, and suggests that feed-forward activation of conditional metabolic pathways through essential metabolites mediates metabolic plasticity.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3