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Regulation in metabolism

An introduction to the basic regulatory mechanisms operating in metabolism
MARK VIANT: Metabolism is regulated by biochemicals, and metabolites act as regulators of other biochemical processes. Previously, the central dogma of biology defined that biological information flowed from the gene, to the transcript, to the protein, to the metabolite. However, this is not necessarily the case in metabolism, where feed-back and feed-forward loops act to regulate these processes and where metabolites can regulate other biochemical processes, for example, gene methylation. As metabolism operates very quickly, it provides a sensor to changes in the environment and can act as a buffering mechanism to compensate for these environmental changes. An example of how metabolites regulate metabolism is glucose regulation in humans.
An increase in the blood glucose concentration following a meal stimulates insulin secretion from the pancreas, which regulates glucose uptake by cells in the liver, and it converts glucose to glycogen for storage. And this, consequently, lowers the blood glucose level.
However, if blood glucose levels fall, the pancreas secretes glucagon and not insulin, resulting in the breakdown of glycogen into glucose and increasing blood glucose levels. Via this mechanism, the concentration of glucose in the blood is controlled and this is termed homeostasis.
If metabolic regulation is impaired, then different outcomes are observed. For example, in diabetes, insulin can be secreted from the pancreas at normal levels. But the effect of the insulin on regulating the cellular uptake of glucose is decreased, and, consequently, blood glucose concentrations remain high after a meal. By monitoring changes in metabolite concentrations, we can determine when a biological system is behaving normally and when its metabolism shifts away from homeostasis. Departures from normal metabolism can indicate the onset of a disease. For example, a high level of glucose in blood or in the urine can be used to actually diagnose diabetes.

The central dogma of biology provides the framework for the flow of genetic material from the gene to the transcript, protein and metabolite. However, in metabolism, metabolites act as regulators of other biochemical processes, with feed-back and feed-forward loops regulating these processes.

Professor Mark Viant describes the basic regulatory mechanism operating in metabolism with specific examples to highlight the biological relevance.

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Metabolomics: Understanding Metabolism in the 21st Century

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