In enzymology, a 2-dehydro-3-deoxy-D-gluconate 5-dehydrogenase (EC 1.1.1.127) is an enzyme that catalyzes the chemical reaction

2-dehydro-3-deoxy-D-gluconate + NAD⁺ ${\displaystyle \rightleftharpoons }$ (4S)-4,6-dihydroxy-2,5-dioxohexanoate + NADH + H⁺

Thus, the two substrates of this enzyme are 2-dehydro-3-deoxy-D-gluconate and NAD⁺, whereas its 3 products are (4S)-4,6-dihydroxy-2,5-dioxohexanoate, NADH, and H⁺.

This enzyme participates in pentose and glucuronate interconversions.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD⁺ or NADP⁺ as acceptor. The systematic name of this enzyme class is 2-dehydro-3-deoxy-D-gluconate:NAD⁺ 5-oxidoreductase. Other names in common use include 2-keto-3-deoxygluconate 5-dehydrogenase, 2-keto-3-deoxy-D-gluconate dehydrogenase, 2-keto-3-deoxygluconate (nicotinamide adenine dinucleotide, (phosphate)) dehydrogenase, 2-keto-3-deoxy-D-gluconate (3-deoxy-D-glycero-2,5-hexodiulosonic, and acid) dehydrogenase.

• Condemine G; Hugouvieux-Cotte-Pattat N; Robert-Baudouy J (1984). "An enzyme in the pectolytic pathway of Erwinia chrysanthemi: 3-keto-3-deoxygluconate oxidoreductase". J. Gen. Microbiol. 130 (11): 2839–2844. doi:10.1099/00221287-130-11-2839.
• Preiss J, Ashwell G (May 1963). "Polygalacturonic acid metabolism in bacteria. II. Formation and metabolism of 3-deoxy-D-glycero-2, 5-hexodiulosonic acid". The Journal of Biological Chemistry. 238 (5): 1577–83. doi:10.1016/S0021-9258(18)81103-6. PMID 13986017.