Regulation of acetate metabolism by protein phosphorylation in enteric bacteria

Annu Rev Microbiol. 1998:52:127-64. doi: 10.1146/annurev.micro.52.1.127.

Abstract

Growth of enteric bacteria on acetate as the sole source of carbon and energy requires operation of a particular anaplerotic pathway known as the glyoxylate bypass. In this pathway, two specific enzymes, isocitrate lyase and malate synthase, are activated to divert isocitrate from the tricarboxylic acid cycle and prevent the quantitative loss of acetate carbons as carbon dioxide. Bacteria are thus supplied with the metabolic intermediates they need for synthesizing their cellular components. The channeling of isocitrate through the glyoxylate bypass is regulated via the phosphorylation/dephosphorylation of isocitrate dehydrogenase, the enzyme of the tricarboxylic acid cycle which competes for a common substrate with isocitrate lyase. When bacteria are grown on acetate, isocitrate dehydrogenase is phosphorylated and, concomitantly, its activity declines drastically. Conversely, when cells are cultured on a preferred carbon source, such as glucose, the enzyme is dephosphorylated and recovers full activity. Such reversible phosphorylation is mediated by an unusual bifunctional enzyme, isocitrate dehydrogenase kinase/phosphatase, which contains both modifying and demodifying activities on the same polypeptide. The genes coding for malate synthase, isocitrate lyase, and isocitrate dehydrogenase kinase/phosphatase are located in the same operon. Their expression is controlled by a complex dual mechanism that involves several transcriptional repressors and activators. Recent developments have brought new insights into the nature and mode of action of these different regulators. Also, significant advances have been made lately in our understanding of the control of enzyme activity by reversible phosphorylation. In general, analyzing the physiological behavior of bacteria on acetate provides a valuable approach for deciphering at the molecular level the mechanisms of cell adaptation to the environment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetates / metabolism*
  • Bacterial Proteins / metabolism
  • Citric Acid Cycle
  • Enterobacteriaceae / genetics
  • Enterobacteriaceae / metabolism
  • Enterobacteriaceae / physiology*
  • Enzyme Activation
  • Genes, Bacterial
  • Glyoxylates / metabolism
  • Isocitrate Dehydrogenase / genetics
  • Isocitrate Dehydrogenase / metabolism
  • Isocitrate Lyase / genetics
  • Isocitrate Lyase / metabolism
  • Malate Synthase / genetics
  • Operon / genetics
  • Phosphorylation
  • Repressor Proteins / genetics

Substances

  • Acetates
  • Bacterial Proteins
  • Glyoxylates
  • Repressor Proteins
  • Isocitrate Dehydrogenase
  • Malate Synthase
  • Isocitrate Lyase
  • glyoxylic acid