NADPH Production by the Pentose Phosphate Pathway in the Zona Fasciculata of Rat Adrenal Gland

Wilma M. Frederiks ¹, Intan P.E.D. Kümmerlin ¹, Klazina S. Bosch ¹, Heleen Vreeling-Sindelárova ¹, Ard Jonker ¹ and Cornelis J.F. Van Noorden ^1*

¹ Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

^* To whom correspondence should be addressed. E-mail: c.j.vannoorden{at}amc.uva.nl.

Submitted on February 28, 2007
Accepted on 14 May 2007

	Abstract

Biosynthesis of steroid hormones in the cortex of the adrenal gland takes place in smooth endoplasmic reticulum and mitochondria and requires NADPH. Four enzymes produce NADPH: glucose-6-phosphate dehydrogenase (G6PD), the key regulatory enzyme of the pentose phosphate pathway, phosphogluconate dehydrogenase (PGD), the third enzyme of that pathway, malate dehydrogenase (MDH) and isocitrate dehydrogenase (ICDH). However, the contribution of each enzyme to NADPH production in the cortex of adrenal gland has not been established. Therefore, activity of G6PD, PGD, MDH and ICDH was localized and quantified in rat adrenocortical tissue using metabolic mapping, image analysis and electron microscopy. The four enzymes have similar localization patterns in adrenal gland with highest activities in the zona fasciculata of the cortex. G6PD activity was strongest, PGD, MDH and ICDH activity was approximately 60, 15 and 7% of G6PD activity, respectively. The K_m value of G6PD for glucose-6-phosphate was twice higher than the K_m value of PGD for phosphogluconate. As a consequence, virtual flux rates through G6PD and PGD are largely similar. It is concluded that G6PD and PGD provide the major part of NADPH in adrenocortical cells. Their activity is localized in the cytoplasm associated with free ribosomes and membranes of the smooth endoplasmic reticulum indicating that NADPH-demanding processes related with biosynthesis of steroid hormones take place at these sites. The complete inhibition of G6PD by androsterones suggests that there is feed back regulation of steroid hormone hormone via G6PD.

Key Words: NADPH, adrenal gland, glucose-6-phosphate dehydrogenase, phosphogluconate dehydrogenase

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