Transfer of reducing equivalents into mitochondria by the interconversions of proline and Δ1-pyrroline-5-carboxylate |
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Authors: | Curt H Hagedorn James M Phang |
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Institution: | Endocrinology Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20205 U.S.A. |
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Abstract: | Direct evidence is presented for a proline cycle using a cell-free experimental system which sequentially transfers 3H from 1-3H]glucose to NADP+ to Δ1-pyrroline-5-carboxylate and yields 3H]proline. The formation of 3H]proline depends on the presence of NADP, Δ1-pyrroline-5-carboxylate, and the enzymes glucose-6-phosphate dehydrogenase and Δ1-pyrroline-5-carboxylate reductase. The production of 3H]proline from unlabeled proline in the presence of mitochondria provides direct evidence for one complete turn of a proline cycle which transfers reducing equivalents produced by glucose oxidation in the pentose pathway into mitochondria. In this cycle, proline is oxidized to Δ1-pyrroline-5-carboxylate by mitochondrial proline oxidase. Δ1-pyrroline-5-carboxylate is released from mitochondria and is recycled back to proline by Δ1-pyrroline-5-carboxylate reductase with concomitant oxidation of NADPH. At the maximal rate observed, 60% of Δ1-pyrroline-5-carboxylate produced is recycled back to proline. This cycle provides a mechanism for transferring reducing equivalents from NADPH into mitochondria and is linked to glucose oxidation in the pentose pathway by NADPH turnover. |
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Keywords: | To whom correspondence should be addressed |
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