With the exception of the oxidation of G6P (glucose 6-phosphate) by H6PDH (hexose-6-phosphate dehydrogenase), scant information is available about other endogenous substrates affecting the redox state or the regulation of key enzymes which govern the ratio of the pyridine nucleotide NADPH/NADP. In isolated rat liver microsomes, NADPH production was increased, as anticipated, by G6P; however, this was strikingly amplified by palmitoylcarnitine. Subsequent experiments revealed that the latter compound, well within its physiological concentration range, inhibited 11β-HSD1 (11β-hydroxysteroid dehydrogenase 1), the bidirectional enzyme which interconnects inactive 11-oxo steroids and their active 11-hydroxy derivatives. Notably, palmitoylcarnitine also stimulated the antithetical direction of 11β-HSD1 reductase, namely dehydrogenase. This stimulation of H6PDH may have likewise contributed to the NADPH accretion. All told, the result of these enzyme modifications is, in a conjoint fashion, a sharp amplification of microsomal NADPH production. Neither the purified 11β-HSD1 nor that obtained following microsomal sonification were sensitive to palmitoylcarnitine inhibition. This suggests that the long-chain amphipathic acylcarnitines, given their favourable partitioning into the membrane lipid bilayer, disrupt the proficient kinetic and physical interplay between 11β-HSD1 and H6PDH. Finally, although IDH (isocitrate dehydrogenase) and malic enzyme are present in microsomes and increase NADPH concentration akin to that of G6P, neither had an effect on 11β-HSD1 reductase, evidence that the NADPH pool in the endoplasmic reticulum shared by the H6PDH/11β-HSD1 alliance is uncoupled from that governed by IDH and malic enzyme.
Skip Nav Destination
Article navigation
July 2011
- Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
June 14 2011
Manifold effects of palmitoylcarnitine on endoplasmic reticulum metabolism: 11β-hydroxysteroid dehydrogenase 1, flux through hexose-6-phosphate dehydrogenase and NADPH concentration
Xudong Wang;
Xudong Wang
*Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35233, U.S.A.
Search for other works by this author on:
Gail J. Mick;
Gail J. Mick
*Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35233, U.S.A.
Search for other works by this author on:
Edmund Maser;
Edmund Maser
†Institute of Toxicology and Pharmacology for Natural Scientists, University Medical School Schleswig-Holstein, Campus Kiel, Brunswiker Str. 10, 24105 Kiel, Germany
Search for other works by this author on:
Kenneth McCormick
Kenneth McCormick
1
*Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35233, U.S.A.
1To whom correspondence should be addressed (email kmccormick@peds.uab.edu).
Search for other works by this author on:
Biochem J (2011) 437 (1): 109–115.
Article history
Received:
December 09 2010
Revision Received:
April 06 2011
Accepted:
April 15 2011
Accepted Manuscript online:
April 15 2011
Citation
Xudong Wang, Gail J. Mick, Edmund Maser, Kenneth McCormick; Manifold effects of palmitoylcarnitine on endoplasmic reticulum metabolism: 11β-hydroxysteroid dehydrogenase 1, flux through hexose-6-phosphate dehydrogenase and NADPH concentration. Biochem J 1 July 2011; 437 (1): 109–115. doi: https://doi.org/10.1042/BJ20102069
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.