Pyridine nucleotide metabolism by extracts derived from Haemophilus parasuis and H. pleuropneumoniae

1986 ◽  
Vol 32 (9) ◽  
pp. 733-737 ◽  
Author(s):  
T. O'Reilly ◽  
D. F. Niven
Keyword(s):  
Pyridine Nucleotide ◽  
Nucleotide Metabolism ◽  
Haemophilus Parasuis ◽  
Pyridine Nucleotides ◽  
Nicotinamide Riboside ◽  
Cell Fractions

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.

scholarly journals Resveratrol Stimulates Cortisol Biosynthesis by Activating SIRT-Dependent Deacetylation of P450scc

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 3258-3268 ◽  
Author(s):  
Donghui Li ◽  
Eric B. Dammer ◽  
Marion B. Sewer
Keyword(s):  
Protein Expression ◽  
Fold Increase ◽  
Pyridine Nucleotide ◽  
Nucleotide Metabolism ◽  
Side Chain ◽  
Mitochondrial Enzyme ◽  
Adrenocortical Cells ◽  
Protein Levels ◽  
Chain Cleavage ◽  
Cleavage Enzyme

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.

scholarly journals PnuT uses a facilitated diffusion mechanism for thiamine uptake

2017 ◽  
Vol 150 (1) ◽  
pp. 41-50 ◽  
Author(s):  
Michael Jaehme ◽  
Rajkumar Singh ◽  
Alisa A. Garaeva ◽  
Ria H. Duurkens ◽  
Dirk-Jan Slotboom
Keyword(s):  
Substrate Binding ◽  
Diffusion Mechanism ◽  
Vitamin B1 ◽  
Pyridine Nucleotide ◽  
Thiamine Pyrophosphate ◽  
Facilitated Diffusion ◽  
Nicotinamide Riboside ◽  
Thiamine Transport ◽  
Shewanella Woodyi ◽  
Thiamine Analogues

Membrane transporters of the bacterial pyridine nucleotide uptake (Pnu) family mediate the uptake of various B-type vitamins. For example, the PnuT transporters have specificity for vitamin B1 (thiamine). It has been hypothesized that Pnu transporters are facilitators that allow passive transport of the vitamin substrate across the membrane. Metabolic trapping by phosphorylation would then lead to accumulation of the transported substrates in the cytoplasm. However, experimental evidence for such a transport mechanism is lacking. Here, to determine the mechanism of thiamine transport, we purify PnuTSw from Shewanella woodyi and reconstitute it in liposomes to determine substrate binding and transport properties. We show that the electrochemical gradient of thiamine solely determines the direction of transport, consistent with a facilitated diffusion mechanism. Further, PnuTSw can bind and transport thiamine as well as the thiamine analogues pyrithiamine and oxythiamine, but does not recognize the phosphorylated derivatives thiamine monophosphate and thiamine pyrophosphate as substrates, consistent with a metabolic trapping mechanism. Guided by the crystal structure of the homologous nicotinamide riboside transporter PnuC, we perform mutagenesis experiments, which reveal residues involved in substrate binding and gating. The facilitated diffusion mechanism of transport used by PnuTSw contrasts sharply with the active transport mechanisms used by other bacterial thiamine transporters.

scholarly journals Regulation of Pyridine Nucleotide Metabolism During Tomato Fruit Development Through Transcript and Protein Profiling

2019 ◽  
Vol 10 ◽  
Author(s):  
Guillaume Decros ◽  
Bertrand Beauvoit ◽  
Sophie Colombié ◽  
Cécile Cabasson ◽  
Stéphane Bernillon ◽  
...  
Keyword(s):  
Fruit Development ◽  
Tomato Fruit ◽  
Pyridine Nucleotide ◽  
Nucleotide Metabolism ◽  
Protein Profiling

scholarly journals Impaired erythrocyte phosphoribosylpyrophosphate formation in hemolytic anemia due to pyruvate kinase deficiency

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 500-506 ◽  
Author(s):  
CR Zerez ◽  
MD Wong ◽  
NA Lachant ◽  
KR Tanaka
Keyword(s):  
Pyruvate Kinase ◽  
Hemolytic Anemia ◽  
Adenosine Triphosphate ◽  
Pyridine Nucleotide ◽  
Pentose Phosphate ◽  
Atp Depletion ◽  
Pyridine Nucleotides ◽  
Pyruvate Kinase Deficiency ◽  
Nucleotide Content ◽  
Pentose Phosphate Shunt

Abstract RBCs from patients with hemolytic anemia due to pyruvate kinase (PK) deficiency are characterized by a decreased total adenine and pyridine nucleotide content. Because phosphoribosylpyrophosphate (PRPP) is a precursor of both adenine and pyridine nucleotides, we investigated the ability of intact PK-deficient RBCs to accumulate PRPP. The rate of PRPP formation in normal RBCs (n = 11) was 2.89 +/- 0.80 nmol/min.mL RBCs. In contrast, the rate of PRPP formation in PK-deficient RBCs (n = 4) was markedly impaired at 1.03 +/- 0.39 nmol/min.mL RBCs. Impaired PRPP formation in these cells was not due to the higher proportion of reticulocytes. To study the mechanism of impaired PRPP formation, PK deficiency was simulated by incubating normal RBCs with fluoride. In normal RBCs, fluoride inhibited PRPP formation, caused adenosine triphosphate (ATP) depletion, prevented 2,3-diphosphoglycerate (DPG) depletion, and inhibited pentose phosphate shunt (PPS) activity. These results together with other data suggest that impaired PRPP formation is mediated by changes in ATP and DPG concentration, which lead to decreased PPS and perhaps decreased hexokinase and PRPP synthetase activities. Impaired PRPP formation may be a mechanism for the decreased adenine and pyridine nucleotide content in PK-deficient RBCs.

Decreased erythrocyte nicotinamide adenine dinucleotide redox potential and abnormal pyridine nucleotide content in sickle cell disease

Blood ◽  
1988 ◽  
Vol 71 (2) ◽  
pp. 512-515 ◽  
Author(s):  
CR Zerez ◽  
NA Lachant ◽  
SJ Lee ◽  
KR Tanaka
Keyword(s):  
Sickle Cell Disease ◽  
Redox Potential ◽  
Sickle Cell ◽  
Nicotinamide Adenine Dinucleotide ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Pyridine Nucleotide ◽  
Nicotinamide Adenine ◽  
Pyridine Nucleotides ◽  
Cell Disease ◽  
Sickle Erythrocyte

Abstract RBCs from individuals with sickle cell disease are more susceptible to oxidant damage. Because key antioxidant defense reactions are linked to the pyridine nucleotides nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), we tested the hypothesis that the RBC redox potential as manifested by the NADH/[NAD+ + NADH] and NADPH/[NADP+ + NADPH] ratios is decreased in sickle erythrocytes. Our data demonstrate that sickle RBCs have a significant decrease in the NADH/[NAD+ + NADH] ratio compared with normal RBCs (P less than .00005). Interestingly, sickle RBCs also had a significant increase in total NAD content compared with normal RBCs (P less than .00005). In contrast, although sickle RBCs had a significant increase in the total NADP content compared with normal RBCs (P less than .00005), sickle RBCs had no significant alteration in the NADPH/[NADP+ + NADPH] ratio. High reticulocyte controls demonstrated that these changes were not related to cell age. Thus, sickle RBCs have a decrease in NAD redox potential that may be a reflection of their increased oxidant sensitivity. The changes in these pyridine nucleotides may have further metabolic consequences for the sickle erythrocyte.

scholarly journals Identification by photoaffinity labelling of a pyridine nucleotide-dependent tri-iodothyronine-binding protein in the cytosol of cultured astroglial cells

1995 ◽  
Vol 305 (3) ◽  
pp. 729-737 ◽  
Author(s):  
A Beslin ◽  
M P Vié ◽  
J P Blondeau ◽  
J Francon
Keyword(s):  
Total Concentration ◽  
Gradient Centrifugation ◽  
Pyridine Nucleotide ◽  
Free Radical Scavenger ◽  
Maximum Effect ◽  
Radical Scavenger ◽  
Pyridine Nucleotides ◽  
Astroglial Cells ◽  
Nadph Oxidation ◽  
Oxidation System

High-affinity 3,3′,5-tri-iodo-L-thyronine (T3) binding (Kd approximately 0.3 nM) to the cytosol of cultured rat astroglial cells was strongly activated in the presence of pyridine nucleotides. A 35 kDa pyridine nucleotide-dependent T3-binding polypeptide (35K-TBP) was photoaffinity labelled using underivatized [125I]T3 in the presence of pyridine nucleotides and the free-radical scavenger dithiothreitol. Maximum activations of T3 binding and 35K-TBP photolabelling were obtained at approx. 1 x 10(-7) M NADP+ or NADPH, or 1 x 10(-4) M NADH. NAD+ and other nucleotides were without effect. NADPH is the form which activates T3 binding and 35K-TBP photolabelling, since cytosol contains NADP(+)-reducing activity, and the activation of both processes in the presence of NADPH and NADP+ was prevented by an exogenous NADPH oxidation system. NADPH behaved as an allosteric activator of T3 binding. The NADPH oxidation system promoted the release of bound T3 in the absence of any change in the total concentration of the hormone. The 35K-TBP photolabelling and [125I]T3 binding were similarly inhibited by non-radioactive T3 (half-maximum effect at 0.5-1.0 nM T3). The concentrations of iodothyronine analogues that inhibited both processes were correlated (3,3′,5-tri-iodo-D-thyronine > or = T3 > L-thyroxine > tri-iodothyroacetic acid > 3,3′5′-tri-iodo-L-thyronine). Molecular sieving and density-gradient centrifugation of cytosol identified a 65 kDa T3-binding entity, which included the 35K-TBP. These results indicate that 35K-TBP is the cytosolic entity involved in the pyridine nucleotide-dependent T3 binding, and suggest that the sequestration and release of intracellular thyroid hormones are regulated by the redox state of astroglial cell compartment(s).

Redox studies of the epiphyseal growth cartilage: Pyridine nucleotide metabolism and the development of mineralization

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