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Module 13 - Principles of Metabolic Regulation Module 13 Lecture 1 Regulation of Metabolic Pathways In a metabolically active cell in a steady state, intermediates are formed and consumed at equal rates. When a transient perturbation alters the rate of formation or consumption of a metabolite, compensating changes in enzyme activities return the system to the steady state. Cells regulate their metabolism by a variety of mechanisms over a time scale ranging from less than a millisecond to days, either by changing the activity of existing enzyme molecules or by changing the number of molecules of a specific enzyme. Various signals activate or inactivate transcription factors, which act in the nucleus to regulate gene expression. Changes in the transcriptome lead to changes in the proteome, and ultimately in the metabolome of a cell or tissue. In multistep processes such as glycolysis, certain reactions are essentially at equilibrium in the steady state; the rates of these reactions rise and fall with substrate concentration. Other reactions are far from equilibrium; these steps are typically the points of regulation of the overall pathway. Regulatory mechanisms maintain nearly constant levels of key metabolites such as ATP and NADH in cells and glucose in the blood, while matching the use or production of glucose to the organism’s changing needs. The levels of ATP and AMP are a sensitive reflection of a cell’s energy status, and when the [ATP]/[AMP] ratio decreases, the AMP-activated protein kinase (AMPK) triggers a variety of cellular responses to raise [ATP] and lower [AMP]. Module 13 Lecture 2 Analysis of Metabolic Control Metabolic control analysis shows that control of the rate of metabolite flux through a pathway is distributed among several of the enzymes in that path. The flux control coefficient, C, is an experimentally determined measure of the effect of an enzyme’s
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