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A Mathematical Model for Enzyme Clustering in Glucose Metabolism.

Abstract：

:We have recently demonstrated that the rate-limiting enzymes in human glucose metabolism organize into cytoplasmic clusters to form a multienzyme complex, the glucosome, in at least three different sizes. Quantitative high-content imaging data support a hypothesis that the glucosome clusters regulate the direction of glucose flux between energy metabolism and building block biosynthesis in a cluster size-dependent manner. However, direct measurement of their functional contributions to cellular metabolism at subcellular levels has remained challenging. In this work, we develop a mathematical model using a system of ordinary differential equations, in which the association of the rate-limiting enzymes into multienzyme complexes is included as an essential element. We then demonstrate that our mathematical model provides a quantitative principle to simulate glucose flux at both subcellular and population levels in human cancer cells. Lastly, we use the model to simulate 2-deoxyglucose-mediated alteration of glucose flux in a population level based on subcellular high-content imaging data. Collectively, we introduce a new mathematical model for human glucose metabolism, which promotes our understanding of functional roles of differently sized multienzyme complexes in both single-cell and population levels.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Jeon M,Kang HW,An S

doi

10.1038/s41598-018-20348-7

subject

Has Abstract

pub_date

2018-02-09 00:00:00

pages

2696

issue

1

issn

2045-2322

pii

10.1038/s41598-018-20348-7

journal_volume

8

pub_type

杂志文章

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