scholarly journals Pyridine Nucleotide Metabolism: Mechanism of Action of the Niacin Antagonist, 6-Aminonicotinamide

1958 ◽  
Vol 233 (4) ◽  
pp. 964-968
Author(s):  
L.S. Dietrich ◽  
Ira M. Friedland ◽  
Leatrice A. Kaplan
Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 3258-3268 ◽  
Author(s):  
Donghui Li ◽  
Eric B. Dammer ◽  
Marion B. Sewer

In the human adrenal cortex, cortisol is synthesized from cholesterol by members of the cytochrome P450 superfamily and hydroxysteroid dehydrogenases. Both the first and last steps of cortisol biosynthesis occur in mitochondria. Based on our previous findings that activation of ACTH signaling changes the ratio of nicotinamide adenine dinucleotide (NAD) phosphate to reduced NAD phosphate in adrenocortical cells, we hypothesized that pyridine nucleotide metabolism may regulate the activity of the mitochondrial NAD+-dependent sirtuin (SIRT) deacetylases. We show that resveratrol increases the protein expression and half-life of P450 side chain cleavage enzyme (P450scc). The effects of resveratrol on P450scc protein levels and acetylation status are dependent on SIRT3 and SIRT5 expression. Stable overexpression of SIRT3 abrogates the cellular content of acetylated P450scc, concomitant with an increase in P450scc protein expression and cortisol secretion. Mutation of K148 and K149 to alanine stabilizes the expression of P450scc and results in a 1.5-fold increase in pregnenolone biosynthesis. Finally, resveratrol also increases the protein expression of P450 11β, another mitochondrial enzyme required for cortisol biosynthesis. Collectively, this study identifies a role for NAD+-dependent SIRT deacetylase activity in regulating the expression of mitochondrial steroidogenic P450.


2019 ◽  
Vol 10 ◽  
Author(s):  
Guillaume Decros ◽  
Bertrand Beauvoit ◽  
Sophie Colombié ◽  
Cécile Cabasson ◽  
Stéphane Bernillon ◽  
...  

2009 ◽  
Vol 1 (5) ◽  
pp. 433-440 ◽  
Author(s):  
Saburo Kakuta ◽  
Ellis E. Golub ◽  
John C. Haselgrove ◽  
Britton Chance ◽  
Peter Frasca ◽  
...  

1976 ◽  
Vol 14 (3-4) ◽  
pp. 197-207 ◽  
Author(s):  
Ted W. Keyes ◽  
Baldomero M. Olivera ◽  
D. J. Stewart ◽  
E. W. Hanly

1986 ◽  
Vol 32 (9) ◽  
pp. 733-737 ◽  
Author(s):  
T. O'Reilly ◽  
D. F. Niven

A variety of biologically important pyridine nucleotides and precursors were examined for their capacities to serve as substrates for the synthesis of NAD by cell fractions derived from Haemophilus parasuis and H. pleuropneumoniae. Of the compounds tested, only NMN and nicotinamide riboside were converted to NAD. These reactions required ATP as co-substrate, and fractions from both organisms could also catalyze the ATP-dependent synthesis of NADP from NAD. In the absence of ATP, and depending on the pyridine compound under study, NAD, NMN, nicotinamide riboside, and also nicotinamide, were detected as products of catabolisra. It is concluded that these haemophili possess either three-membered pyridine nucleotide cycles or two-membered cycles with synthetic branches originating with nicotinamide riboside. It is also possible that the pyridine nucleotide cycles of both organisms have nonrecycling branches resulting in the "waste" of usable pyridine compound in the form of nicotinamide.


1995 ◽  
Vol 26 (06) ◽  
pp. 288-292 ◽  
Author(s):  
M. Rocchigiani ◽  
S. Sestini ◽  
V. Micheli ◽  
M. Pescaglini ◽  
G. Jacomelli ◽  
...  

Nature ◽  
1961 ◽  
Vol 189 (4764) ◽  
pp. 593-594 ◽  
Author(s):  
G. S. CHRISTIE ◽  
R. N. LEPAGE ◽  
MARGOT J. BAILIE

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