scholarly journals Benzoyl-CoA Reductase (Dearomatizing), A Key Enzyme of Anaerobic Aromatic Metabolism. A Study of Adenosinetriphosphatase Activity, ATP Stoichiometry of the Reaction and EPR Properties of the Enzyme

1997 ◽  
Vol 244 (3) ◽  
pp. 840-851 ◽  
Author(s):  
Matthias Boll ◽  
Simon S. P. Albracht ◽  
Georg Fuchs
Keyword(s):  
Aromatic Metabolism ◽  
Anaerobic Aromatic Metabolism ◽  
Key Enzyme ◽  
Coa Reductase

The Natural Products as Hydroxymethylglutaryl-Coa Reductase Inhibitors

2019 ◽  
Vol 16 (10) ◽  
pp. 1130-1137
Author(s):  
Hayrettin Ozan Gulcan ◽  
Serkan Yigitkan ◽  
Ilkay Erdogan Orhan
Keyword(s):  
Natural Products ◽  
Cardiovascular System ◽  
High Cholesterol ◽  
Chemical Structures ◽  
Reductase Inhibitors ◽  
Key Enzyme ◽  
Serious Disease ◽  
Coa Reductase ◽  
Hydroxymethylglutaryl Coa Reductase ◽  
Alternative Drugs

High cholesterol and triglyceride levels are mainly related to further generation of lifethreating metabolism disorders including cardiovascular system diseases. Therefore, hypercholesterolemia (i.e., also referred to as hyperlipoproteinemia) is a serious disease state, which must be controlled. Currently, the treatment of hypercholesterolemia is mainly achieved through the employment of statins in the clinic, although there are alternative drugs (e.g., ezetimibe, cholestyramine). In fact, the original statins are natural products directly obtained from fungi-like molds and mushrooms and they are potent inhibitors of hydroxymethylglutaryl-CoA reductase, the key enzyme in the biosynthesis of cholesterol. This review focuses on the first identification of natural statins, their synthetic and semi-synthetic analogues, and the validation of hydroxymethylglutaryl-CoA reductase as a target in the treatment of hypercholesterolemia. Furthermore, other natural products that have been shown to possess the potential to inhibit hydroxymethylglutaryl-CoA reductase are also reviewed with respect to their chemical structures.

scholarly journals Statin-Induced Autoimmune Necrotizing Myopathy

2021 ◽  
Vol 12 ◽  
pp. 215013272110287
Author(s):  
Sahani Jayatilaka ◽  
Kunal Desai ◽  
Swarup Rijal ◽  
Debra Zimmerman
Keyword(s):  
Renal Failure ◽  
Statin Therapy ◽  
Initial Presentation ◽  
Autoimmune Reaction ◽  
Necrotizing Myopathy ◽  
Starting Dose ◽  
Key Enzyme ◽  
Risk Patients ◽  
Autoimmune Myopathy ◽  
Coa Reductase

Statin therapy is a widely prescribed medication class for hypercholesterolemia. In statin-induced autoimmune myopathy, genetically predisposed and at-risk patients can develop antibodies against hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the key enzyme in the production of cholesterol. As a result, an autoimmune reaction causing weakness, myalgia, with possible severe rhabdomyolysis, renal failure, and myonecrosis also can occur. A 73-year-old female presented to clinic with myalgia and fatigue. She was on atorvastatin 20 mg/day for over 1 year, which she stopped 1 week prior to her initial presentation. Patient did experience rhabdomyolysis as well as a transaminitis. She underwent an autoimmune workup which was positive for HMG-CoA reductase antibodies. Patient was initially treated on a prednisone taper, starting dose 50 mg/day. Without remission of symptoms, methotrexate 15 mg/week was initiated.

scholarly journals In Vitro Activity of Statins against Naegleria fowleri

Pathogens ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 122 ◽  
Author(s):  
Aitor Rizo-Liendo ◽  
Ines Sifaoui ◽  
María Reyes-Batlle ◽  
Olfa Chiboub ◽  
Rubén L. Rodríguez-Expósito ◽  
...  
Keyword(s):  
Vitro Activity ◽  
In Vitro Activity ◽  
Naegleria Fowleri ◽  
Key Factors ◽  
Key Enzyme ◽  
Liver And Kidney ◽  
Nægleria Fowleri ◽  
Coa Reductase ◽  
Effective Drugs

Naegleria fowleri causes a deadly disease called primary amoebic meningoencephalitis (PAM). Even though PAM is still considered a rare disease, the number of reported cases worldwide has been increasing each year. Among the factors to be considered for this, awareness about this disease, and also global warming, as these amoebae thrive in warm water bodies, seem to be the key factors. Until present, no fully effective drugs have been developed to treat PAM, and the current options are amphotericin B and miltefosine, which present side effects such as liver and kidney toxicity. Statins are able to inhibit the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which is a key enzyme for the synthesis of ergosterol of the cell membrane of these amoebae. Therefore, the in vitro activity of a group of statins was tested in this study against two types of strains of Naegleria fowleri. The obtained results showed that fluvastatin was the most effective statin tested in this study and was able to eliminate these amoebae at concentrations of 0.179 ± 0.078 to 1.682 ± 0.775 µM depending on the tested strain of N. fowleri. Therefore, fluvastatin could be a potential novel therapeutic agent against this emerging pathogen.

scholarly journals Purification, Characterization, and Cloning of a Eubacterial 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase, a Key Enzyme Involved in Biosynthesis of Terpenoids

1999 ◽  
Vol 181 (4) ◽  
pp. 1256-1263 ◽  
Author(s):  
Shunji Takahashi ◽  
Tomohisa Kuzuyama ◽  
Haruo Seto
Keyword(s):  
Amino Acid ◽  
Coenzyme A ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Gel Filtration ◽  
Ph Optimum ◽  
Hmg Coa Reductase ◽  
Apparent Homogeneity ◽  
Key Enzyme ◽  
Coa Reductase

ABSTRACT The eubacterial 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (EC 1.1.1.34 ) was purified 3,000-fold fromStreptomyces sp. strain CL190 to apparent homogeneity with an overall yield of 2.1%. The purification procedure consisted of (NH4)2SO4 precipitation, heat treatment and anion exchange, hydrophobic interaction, and affinity chromatographies. The molecular mass of the enzyme was estimated to be 41 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 100 to 105 kDa by gel filtration chromatography, suggesting that the enzyme is most likely to be a dimer. The enzyme showed a pH optimum of around 7.2, with apparent Km values of 62 μM for NADPH and 7.7 μM for HMG-CoA. A gene from CL190 responsible for HMG-CoA reductase was cloned by the colony hybridization method with an oligonucleotide probe synthesized on the basis of the N-terminal sequence of the purified enzyme. The amino acid sequence of the CL190 HMG-CoA reductase revealed several limited motifs which were highly conserved and common to the eucaryotic and archaebacterial enzymes. These sequence conservations suggest a strong evolutionary pressure to maintain amino acid residues at specific positions, indicating that the conserved motifs might play important roles in the structural conformation and/or catalytic properties of the enzyme.

scholarly journals Different statins produce highly divergent changes in gene expression profiles of human hepatoma cells: a pilot study.

2011 ◽  
Vol 58 (4) ◽  
Author(s):  
Agata Leszczynska ◽  
Monika Gora ◽  
Danuta Plochocka ◽  
Grazyna Hoser ◽  
Anna Szkopinska ◽  
...  
Keyword(s):  
Gene Expression ◽  
Statin Therapy ◽  
Hepg2 Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
High Dose ◽  
Human Hepatoma ◽  
Human Hepatoma Cells ◽  
Key Enzyme ◽  
Coa Reductase

Statins are inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the key enzyme of the sterol biosynthesis pathway. Statin therapy is commonly regarded as well tolerated. However, serious adverse effects have also been reported, especially during high-dose statin therapy. The aim of our study was to investigate the effect of statins on gene expression profiles in human hepatoma HepG2 cells using Affymetrix Human Genome U133 Plus 2.0 arrays. Expression of 102, 857 and 1091 genes was changed substantially in HepG2 cells treated with simvastatin, fluvastatin and atorvastatin, respectively. Pathway and gene ontology analysis showed that many of the genes with changed expression levels were involved in a broad range of metabolic processes. The presented data clearly indicate substantial differences between the tested statins.

scholarly journals A catalytically versatile benzoyl-CoA reductase, key enzyme in the degradation of methyl- and halobenzoates in denitrifying bacteria

2018 ◽  
Vol 293 (26) ◽  
pp. 10264-10274 ◽  
Author(s):  
Oliver Tiedt ◽  
Jonathan Fuchs ◽  
Wolfgang Eisenreich ◽  
Matthias Boll
Keyword(s):  
Denitrifying Bacteria ◽  
Key Enzyme ◽  
Coa Reductase

scholarly journals Expressional diversity of grapevine 3-Hydroxy-3-methylglutaryl-CoA reductase (VvHMGR) in different grapes genotypes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ting Zheng ◽  
Lubin Guan ◽  
Kun Yu ◽  
Muhammad Salman Haider ◽  
Maazullah Nasim ◽  
...  
Keyword(s):  
Tissue Specificity ◽  
Carotenoid Biosynthesis ◽  
Expression Level ◽  
Uv Treatment ◽  
Mva Pathway ◽  
Grape Fruit ◽  
Key Enzyme ◽  
Coa Reductase ◽  
Ggpp Synthase

Abstract Background 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGR) is a key enzyme in the mevalonate (MVA) pathway, which regulates the metabolism of terpenoids in the cytoplasm and determines the type and content of downstream terpenoid metabolites. Results Results showed that grapevine HMGR family has three members, such as VvHMGR1, VvHMGR2, and VvHMGR3. The expression of VvHMGRs in 'Kyoho' has tissue specificity, for example, VvHMGR1 keeps a higher expression, VvHMGR2 is the lowest, and VvHMGR3 gradually decreases as the fruit development. VvHMGR3 is closely related to CsHMGR1 and GmHMGR9 and has collinearity with CsHMGR2 and GmHMGR4. By the prediction of interaction protein, it can interact with HMG-CoA synthase, MVA kinase, FPP/GGPP synthase, diphosphate mevalonate decarboxylase, and participates in the synthesis and metabolism of terpenoids. VvHMGR3 have similar trends in expression with some of the genes of carotenoid biosynthesis and MEP pathways. VvHMGR3 responds to various environmental and phytohormone stimuli, especially salt stress and ultraviolet (UV) treatment. The expression level of VvHMGRs is diverse in grapes of different colors and aroma. VvHMGRs are significantly higher in yellow varieties than that in red varieties, whereas rose-scented varieties showed significantly higher expression than that of strawberry aroma. The expression level is highest in yellow rose-scented varieties, and the lowest in red strawberry scent varieties, especially ‘Summer Black’ and ‘Fujiminori’. Conclusion This study confirms the important role of VvHMGR3 in the process of grape fruit coloring and aroma formation, and provided a new idea to explain the loss of grape aroma and poor coloring during production. There may be an additive effect between color and aroma in the HMGR expression aspect.

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