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6-Phosphogluconate dehydrogenase: the mechanism of action investigated by a comparison of the enzyme from different species.
Biochim Biophys Acta. 1998 Dec 08; 1429(1):83-92.BB

Abstract

The mechanism of action of 6-phosphogluconate dehydrogenase with the alternative substrate 2-deoxy 6-phosphogluconate was investigated using enzymes from sheep liver, human erythrocytes and Trypanosoma brucei. The three enzymes oxidize 2-deoxy 6-phosphogluconate, but only the sheep liver enzyme releases the intermediate 2-deoxy,3-keto 6-phosphogluconate. Kinetic comparison showed that an increase in the rate of NADP+ reduction at high pH is due to increased release of the intermediate, rather than an increase in the overall reaction rate. 2-Deoxy,3-keto 6-phosphogluconate is decarboxylated by the erythrocyte and trypanosome enzymes but not the liver one in the absence of either NADPH or 6-phosphogluconate, which act as activators. The pH dependence of decarboxylation and the degree of activation suggest that 6-phosphogluconate is the activator which operates under normal assay conditions, while NADPH acts mainly by increasing the binding of the intermediate. The data suggest that the activity of 6PGDH is subjected to a two-way regulation: NADPH, which regulates the pentose phosphate pathway, inhibits the enzyme, while 6-phosphogluconate, levels of which rise when NADPH inhibition is removed, acts as an activator ensuring that 6-phosphogluconate is rapidly removed.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, University, Ferrara, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9920387

Citation

Rippa, M, et al. "6-Phosphogluconate Dehydrogenase: the Mechanism of Action Investigated By a Comparison of the Enzyme From Different Species." Biochimica Et Biophysica Acta, vol. 1429, no. 1, 1998, pp. 83-92.
Rippa M, Giovannini PP, Barrett MP, et al. 6-Phosphogluconate dehydrogenase: the mechanism of action investigated by a comparison of the enzyme from different species. Biochim Biophys Acta. 1998;1429(1):83-92.
Rippa, M., Giovannini, P. P., Barrett, M. P., Dallocchio, F., & Hanau, S. (1998). 6-Phosphogluconate dehydrogenase: the mechanism of action investigated by a comparison of the enzyme from different species. Biochimica Et Biophysica Acta, 1429(1), 83-92.
Rippa M, et al. 6-Phosphogluconate Dehydrogenase: the Mechanism of Action Investigated By a Comparison of the Enzyme From Different Species. Biochim Biophys Acta. 1998 Dec 8;1429(1):83-92. PubMed PMID: 9920387.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 6-Phosphogluconate dehydrogenase: the mechanism of action investigated by a comparison of the enzyme from different species. AU - Rippa,M, AU - Giovannini,P P, AU - Barrett,M P, AU - Dallocchio,F, AU - Hanau,S, PY - 1999/1/27/pubmed PY - 1999/1/27/medline PY - 1999/1/27/entrez SP - 83 EP - 92 JF - Biochimica et biophysica acta JO - Biochim. Biophys. Acta VL - 1429 IS - 1 N2 - The mechanism of action of 6-phosphogluconate dehydrogenase with the alternative substrate 2-deoxy 6-phosphogluconate was investigated using enzymes from sheep liver, human erythrocytes and Trypanosoma brucei. The three enzymes oxidize 2-deoxy 6-phosphogluconate, but only the sheep liver enzyme releases the intermediate 2-deoxy,3-keto 6-phosphogluconate. Kinetic comparison showed that an increase in the rate of NADP+ reduction at high pH is due to increased release of the intermediate, rather than an increase in the overall reaction rate. 2-Deoxy,3-keto 6-phosphogluconate is decarboxylated by the erythrocyte and trypanosome enzymes but not the liver one in the absence of either NADPH or 6-phosphogluconate, which act as activators. The pH dependence of decarboxylation and the degree of activation suggest that 6-phosphogluconate is the activator which operates under normal assay conditions, while NADPH acts mainly by increasing the binding of the intermediate. The data suggest that the activity of 6PGDH is subjected to a two-way regulation: NADPH, which regulates the pentose phosphate pathway, inhibits the enzyme, while 6-phosphogluconate, levels of which rise when NADPH inhibition is removed, acts as an activator ensuring that 6-phosphogluconate is rapidly removed. SN - 0006-3002 UR - https://www.unboundmedicine.com/medline/citation/9920387/6_Phosphogluconate_dehydrogenase:_the_mechanism_of_action_investigated_by_a_comparison_of_the_enzyme_from_different_species_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0167-4838(98)00222-2 DB - PRIME DP - Unbound Medicine ER -