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Genetics of the Heme Pathway and Its Regulation, Page 1 of 2
< Previous page Next page > /docserver/preview/fulltext/10.1128/9781555816810/9781555815387_Chap08-1.gif /docserver/preview/fulltext/10.1128/9781555816810/9781555815387_Chap08-2.gifAbstract:
In the spring of 1984, the author decided to study the regulation of heme biosynthetic enzymes and thereby contribute in a peripheral way to the B12 project. This review presents a personal view of the pathway for heme biosynthesis and its regulation in the enteric bacteria Salmonella Typhimurium and Escherichia coli. The chapter emphasizes the genetic aspects with some historical perspective. It discusses what is known about regulation of the heme pathway in these bacteria. The HemA protein is quite unstable in cells growing normally, but it is stabilized by more than 10-fold specifically under conditions of heme limitation. The chapter suggests three simple models for HemA regulation. In the first model, the ATP concentration in vivo is postulated to decrease during heme-limited growth to a point that ATP becomes limiting for energy-dependent proteolysis. Second, when the Lon and ClpAP proteases act on HemA, the Km for ATP might be higher than for other substrates. Finally, the third model supposes that the protease-sensitive conformation is stabilized by formation of a disulfide bond, which is favored when the cell has excess oxidation capacity.