An ultrasensitive enzymatic method for measuring mevalonic acid in serum

Matsuoka, Takeshi; Ueda, Shigeru; Matsumoto, Hideyuki; Kawakami, Masanobu

doi:10.1194/jlr.d028621

Cited by 8 publications

(3 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mevalonic acid was quantified by liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS), using positive-ion mode electrospray ionization with a 5500 Q-Trap system (Applied Biosystems, Foster City, CA) as described previously 24 , 25 .…”

Section: Methodsmentioning

confidence: 99%

Yin and Yang Regulation of Liver X Receptor α Signaling Control of Cholesterol Metabolism by Poly(ADP-ribose) polymerase 1

Zhang¹,

Wang²,

Jiang³

et al. 2020

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Liver X receptor α (LXRα) controls a set of key genes involved in cholesterol metabolism. However, the molecular mechanism of this regulation remains unknown. The regulatory role of poly(ADP-ribose) polymerase 1 (PARP1) in cholesterol metabolism in the liver was examined. Activation of PARP1 in the liver suppressed LXRα sensing and prevented upregulation of genes involved in HCD-induced cholesterol disposal. Mechanistically, LXRα was poly(ADP-ribosyl)ated by activated PARP1, which decreased DNA binding capacity of LXRα, thus preventing its recruitment to the target promoter. Intriguingly, we found that unactivated PARP1 was indispensable for LXRα transactivation and target expression. Further exploration identified unactivated PARP1 as an essential component of the LXRα-promoter complex. Taken together, the results indicate that activated PARP1 suppresses LXRα activation through poly(ADP-ribosyl)ation, while unactivated PARP1 promotes LXRα activation through physical interaction. PARP1 is a pivotal regulator of LXRα signaling and cholesterol metabolism in the liver.

show abstract

Section: Methodsmentioning

confidence: 99%

Yin and Yang Regulation of Liver X Receptor α Signaling Control of Cholesterol Metabolism by Poly(ADP-ribose) polymerase 1

Zhang¹,

Wang²,

Jiang³

et al. 2020

Int. J. Biol. Sci.

View full text Add to dashboard Cite

show abstract

“…Scheme 1. Conversion of MA to HMG-CoA by HMG-CoA reductase 19. HMGR converts MA and CoA to HMG-CoA with NAD + as a cofactor.…”

mentioning

confidence: 99%

“…These methods involve enzymatic method, 19 enzyme immunoassay, 20 radioimmunoassay, 21,22 GC-MS methods 3,[23][24][25] and LC-MS/MS assay. [26][27][28][29][30][31] However, their disadvantage is due to the expense of equipment, extensive sample preparation, time consuming, complications as well as radioactive materials.…”

mentioning

confidence: 99%

Development of Mevalonic Acid Biosensor Using Amperometric Technique Based on Nanocomposite of Nicotinamide Adenine Dinucleotide and Carbon Nanotubes

Poo-arporn

Pakapongpan

Khownarumit

et al. 2017

J. Electrochem. Soc.

View full text Add to dashboard Cite

This study reports the development of an amperometric biosensor for quantification of mevalonic acid (MA), which is the first intermediate of HMG-CoA reductase in the isoprenoids biosynthesis pathway and therefore a useful indicator of HMGR activity. This method offers important advantages over previous reports because no radiolabeled substrates or expensive techniques are required, and time of analysis is relatively short. Self-assembled NAD + onto multiwall-carbon nanotubes (MWCNTs) was synthesized for a biosensing system. Adsorption of NAD + on MCWNTs was characterized by X-ray photoelectron spectroscopy (XPS) technique. This biosensor was constructed by modifying a screen-printed carbon electrode (SPCE) with NAD + /MWCNTs nanocomposite. The electrochemical and electrocatalytic behaviors of the modified electrode were studied using amperometry and cyclic voltammetry (CV). The resulting biosensor demonstrated great electrocatalytic activity, good stability and fast response to MA. At the NAD + /MWCNTs-modified SPCE, the catalytic currents are linearly proportional to the concentrations of MA in the wide range from 10 nM to 140 nM with a limit of detection down to 5 nM (S/N = 3), and the biosensor exhibited a sensitivity of 18.3 μA/mM. We measured the interference effect on the MA analysis and the results demonstrated its imperviousness to the effects of haemoglobin, bilirubin and serum albumin. Measurement of mevalonic acid (MA) is of great interest in health monitoring as it is the first intermediate of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) and appears to be a good indicator of HMGR activity. HMGR plays a crucial role in regulating sterol biosynthesis. Its activity is shown as the rate-limiting step in the mevalonate pathway in the isoprenoid metabolism pathway 1,2 and thus is a prime target for the drug development. Biofluid levels of MA can be used as a biomarker for many diseases. For example, the reduction of plasma concentrations and urinary excretion of MA levels is an indirect measure of decreased cholesterol levels. For treatment of hypercholesterolemia, the statin class of drugs are used to block HMGR activity resulting in inhibition of MA synthesis.3,4 Moreover, cholesterol biosynthesis deficiencies cover a heterogeneous group of disorders. Mevalonate kinase is an enzyme located proximally in the pathway of cholesterol and nonsterol isoprene biosynthesis. Its allelic defects can cause hyperimmunoglobulinemia D syndrome (HIDS) and Mevalonic aciduria (MVA). The diagnosis of these diseases can be performed by determining MA concentration in urine followed by enzyme activity determination or mevalonate-5-phosphate (MVAP) detection by isotope dilution UPLC-MS/MS.5 Interestingly, monitoring MA levels in biofluids allows a better understanding of the drug pharmacodynamics, especially with respect to response to statin therapy due to any interindividual variations, and may allow for improvements in patient management and treatment regimes. 6 Furthermore, inhibition of HMGR may be useful for...

show abstract

Analysis of the Impact of Rosuvastatin on Bacterial Mevalonate Production Using a UPLC-Mass Spectrometry Approach

et al. 2016

View full text Add to dashboard Cite

Statins are widely prescribed cholesterol-lowering medications and act through inhibition of the human enzyme 3-methylglutaryl coenzyme A reductase (HMG-R) which produces mevalonate (MVAL), a key substrate for cholesterol biosynthesis. Some important microbial species also express an isoform of HMG-R; however, the nature of the interaction between statins and bacteria is currently unclear and studies would benefit from protocols to quantify MVAL in complex microbial environments. The objective of this study was to develop a protocol for the analytical quantification of MVAL in bacterial systems and to utilise this approach to analyse the effects of Rosuvastatin (RSV) on bacterial MVAL formation. To determine the effective concentration range of RSV, we examined the dose-dependent inhibition of growth in the HMG-R(+) bacterial pathogens Listeria monocytogenes, Staphylococcus aureus and Enterococcus faecium at various concentrations of pure RSV. Growth inhibition generally correlated with a reduction in bacterial MVAL levels, particularly in culture supernatants at high RSV concentrations, as determined using our ultra-performance liquid chromatography mass spectrometry protocol. This work therefore outlines a refined protocol for the analysis of MVAL in microbial cultures and provides evidence for statin-mediated inhibition of bacterial HMG-R. Furthermore, we show that MVAL is readily transported and secreted from bacterial cells into the growth media.

show abstract

An ultrasensitive enzymatic method for measuring mevalonic acid in serum

Cited by 8 publications

References 20 publications

Yin and Yang Regulation of Liver X Receptor α Signaling Control of Cholesterol Metabolism by Poly(ADP-ribose) polymerase 1

Yin and Yang Regulation of Liver X Receptor α Signaling Control of Cholesterol Metabolism by Poly(ADP-ribose) polymerase 1

Development of Mevalonic Acid Biosensor Using Amperometric Technique Based on Nanocomposite of Nicotinamide Adenine Dinucleotide and Carbon Nanotubes

Analysis of the Impact of Rosuvastatin on Bacterial Mevalonate Production Using a UPLC-Mass Spectrometry Approach

Contact Info

Product

Resources

About