Transfer of reducing equivalents into mitochondria by the interconversions of proline and delta 1-pyrroline-5-carboxylate

Arch Biochem Biophys. 1983 Aug;225(1):95-101. doi: 10.1016/0003-9861(83)90010-3.


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 delta 1-pyrroline-5-carboxylate and yields [3H]proline. The formation of [3H]proline depends on the presence of NADP, delta 1-pyrroline-5-carboxylate, and the enzymes glucose-6-phosphate dehydrogenase and delta 1-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 delta 1-pyrroline-5-carboxylate by mitochondrial proline oxidase. delta 1-pyrroline-5-carboxylate is released from mitochondria and is recycled back to proline by delta 1-pyrroline-5-carboxylate reductase with concomitant oxidation of NADPH. At the maximal rate observed, 60% of delta 1-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.

MeSH terms

  • Animals
  • Catalysis
  • Cell-Free System
  • Cytosol / metabolism
  • Glucose / metabolism
  • Glucosephosphate Dehydrogenase / physiology
  • Humans
  • In Vitro Techniques
  • Male
  • Mitochondria, Liver / metabolism*
  • NADP / metabolism
  • Oxidation-Reduction
  • Proline / biosynthesis*
  • Pyrroles / metabolism*
  • Pyrroline Carboxylate Reductases / physiology
  • Rats
  • Rats, Inbred Strains


  • Pyrroles
  • delta-1-pyrroline-5-carboxylate
  • NADP
  • Proline
  • Glucosephosphate Dehydrogenase
  • Pyrroline Carboxylate Reductases
  • Glucose