Evidence for Proline Catabolic Enzymes in the Metabolism of Thiazolidine Carboxylates

Yizi Mao, Javier Seravalli, Thomas G. Smith, Martha Morton, John J. Tanner, Donald F. Becker

Research output: Contribution to journalArticlepeer-review


Thiazolidine carboxylates such as thiazolidine-4-carboxylate (T4C) and thiazolidine-2-carboxylate (T2C) are naturally occurring sulfur analogues of proline. These compounds have been observed to have both beneficial and toxic effects in cells. Given that proline dehydrogenase has been proposed to be a key enzyme in the oxidative metabolism of thioprolines, we characterized T4C and T2C as substrates of proline catabolic enzymes using proline utilization A (PutA), which is a bifunctional enzyme with proline dehydrogenase (PRODH) and l-glutamate-γ-semialdehyde dehydrogenase (GSALDH) activities. PutA is shown here to catalyze the FAD-dependent PRODH oxidation of both T4C and T2C with catalytic efficiencies significantly higher than with proline. Stopped-flow experiments also demonstrate that l-T4C and l-T2C reduce PutA-bound FAD at rates faster than proline. Unlike proline, however, oxidation of T4C and T2C does not generate a substrate for NAD+-dependent GSALDH. Instead, PutA/PRODH oxidation of T4C leads to cysteine formation, whereas oxidation of T2C generates an apparently stable Δ4-thiazoline-2-carboxylate species. Our results provide new insights into the metabolism of T2C and T4C.

Original languageEnglish (US)
Pages (from-to)3610-3620
Number of pages11
Issue number47
StatePublished - Nov 30 2021
Externally publishedYes

Bibliographical note

Funding Information:
Research reported in this publication was supported in part by the National Institute of General Medical Sciences of the National Institutes of Health under award number R01GM065546.

Publisher Copyright:
© 2021 American Chemical Society.


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