Regulation of Proline Utilization in Salmonella Typhimurium: How Do Cells Avoid a Futile Cycle?

Salmonella typhimurium can degrade proline for use as a carbon, nitrogen, or energy source. To determine whether a futile cycle occurs which degrades the proline accumulated by proline biosynthesis, we studied the expression and enzymatic activity of the proline utilization (put) pathway under conditions which increase the concentration of the intracellular proline pools: catabolism of the dipeptide glycyl-proline, overproduction of proline due to a mutation which prevents feedback inhibition of proline biosynthesis, and accumulation of proline due to osmotic stress. The results indicate that: (i) internal proline induces the put genes, but only when accumulated to concentrations greater than the normal proline biosynthetic pool; and (ii) degradation of proline pools accumulated under high osmotic pressure is limited because proline oxidase is directly inhibited under these conditions.