Copyright © 2003 Per Kraulis, Stockholm Bioinformatics Center, SBC

KTH Bioinformatics 2003, lecture 27 Feb 2003 Per Kraulis

Systems Biology

5. Example: Citric acid cycle

The citric acid cycle, also called the Krebs cycle, or TCA (tricarboxylic acid) cycle, is a central part of the respiratory energy metabolism of many organisms. A number of enzymes act on substrates in a cycle, where an acetyl group from acetyl-coenzyme A is covalently added to oxaloacetate and then converted into two molecules of CO2 and reducing equivalents.

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In one of the first experiments using microarrays for monitoring gene expression changes (DeRisi, Iyer and Brown, Science (1997) 278, 680-686), a yeast culture was allowed to grow in glucose-rich medium until the glucose ran out. The metabolism then changes from anaerobic fermentation of glucose to ethanol, to aerobic metabolism of ethanol. This is the so-called diauxic shift. The gene expression data shows a concerted change, where the TCS cycle genes are up-regulated as the glucose level goes down (red labels), at the same time as the glycolysis genes are down-regulated (green).