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HMG-CoA reductase

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https://www.readbyqxmd.com/read/29224355/structural-features-and-domain-movements-controlling-substrate-binding-and-cofactor-specificity-in-class-ii-hmg-coa-reductase
#1
Bradley R Miller, Yan Kung
The key mevalonate pathway enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR) uses the cofactor NAD(P)H to reduce HMG-CoA to mevalonate in the production of countless metabolites and natural products. Although HMGR inhibition by statin drugs is well understood, several mechanistic details of HMGR catalysis remain unresolved, and the structural basis for the wide range in cofactor specificity for either NADH or NADPH among HMGRs from different organisms is also unknown. Here, we present crystal structures of HMGR from Streptococcus pneumoniae (SpHMGR) alongside kinetic data on the enzyme's cofactor preferences...
December 11, 2017: Biochemistry
https://www.readbyqxmd.com/read/29199554/antioxidative-and-inhibitory-effects-of-the-fruiting-body-of-black-lingzhi-mushroom-amauroderma-rugosum-agaricomycetes-on-ldl-oxidation-and-hmg-coa-reductase-activity
#2
Chan Kam Seng, Noorlidah Abdullah, Norhaniza Aminudin
Amauroderma rugosum fruiting bodies possess excellent cardiovascular benefits, including antioxidative, antihyperlipidemic, antihypertensive, antiinflammatory, anti-platelet aggregation, and antithrombotic effects. In this article, we describe our investigations of the in vitro antioxidant activity and in vitro antiatherosclerotic potential through inhibitory effects on low-density lipoprotein (LDL), LDL peroxidation, and 3-hydroxy3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalytic activity using various fruiting body extracts partitioned with an organic solvent...
2017: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/29180648/csa13-inhibits-colitis-associated-intestinal-fibrosis-via-a-formyl-peptide-receptor-like-1-mediated-hmg-coa-reductase-pathway
#3
Chunlan Xu, Sally Ghali, Jiani Wang, David Q Shih, Christina Ortiz, Caroline C Mussatto, Elaine C Lee, Diana H Tran, Jonathan P Jacobs, Venu Lagishetty, Phillip Fleshner, Lori Robbins, Michelle Vu, Tressia C Hing, Dermot P B McGovern, Hon Wai Koon
Many Crohn's disease (CD) patients develop intestinal strictures, which are difficult to prevent and treat. Cationic steroid antimicrobial 13 (CSA13) shares cationic nature and antimicrobial function with antimicrobial peptide cathelicidin. As many functions of cathelicidin are mediated through formyl peptide receptor-like 1 (FPRL1), we hypothesize that CSA13 mediates anti-fibrogenic effects via FPRL1. Human intestinal biopsies were used in clinical data analysis. Chronic trinitrobenzene sulfonic acid (TNBS) colitis-associated intestinal fibrosis mouse model with the administration of CSA13 was used...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29173649/an-obesogenic-diet-enriched-with-blue-mussels-protects-against-weight-gain-and-lowers-cholesterol-levels-in-c57bl-6-mice
#4
Hitesh B Vaidya, Surendiran Gangadaran, Sukhinder K Cheema
Obesity is linked to several health complications, such as cardiovascular disease, insulin resistance, and hypertension. Dyslipidemia in obesity is one of the prime causes for health complications. We have previously shown that blue mussels (BM) are a rich source of omega (n)-3 polyunsaturated fatty acids (PUFA) and increase the mRNA expression of peroxisome-proliferator activated receptor and adiponectin, thereby inducing anti-obesity and insulin sensitizing effects in vitro. However, the in vivo effects of BM on obesity and metabolic regulation are not known...
October 2017: Nutrition Research
https://www.readbyqxmd.com/read/29167270/ubia-prenyltransferase-domain-containing-protein-1-modulates-hmg-coa-reductase-degradation-to-coordinate-synthesis-of-sterol-and-nonsterol-isoprenoids
#5
Marc M Schumacher, Dong-Jae Jun, Brittany M Johnson, Russell A DeBose-Boyd
UbiA prenyltransferase domain-containing protein-1 (UBIAD1) utilizes geranylgeranyl pyrophosphate (GGpp) to synthesize vitamin K2. We previously reported that sterols stimulate binding of UBIAD1 to endoplasmic reticulum (ER)-localized HMG CoA reductase. UBIAD1 binding inhibits sterol-accelerated, ER-associated degradation (ERAD) of reductase, one of several mechanisms for feedback control of this rate-limiting enzyme in the branched pathway that produces cholesterol and nonsterol isoprenoids such as GGpp. Accumulation of GGpp in ER membranes triggers release of UBIAD1 from reductase, permitting its maximal ERAD and ER-to-Golgi transport of UBIAD1...
November 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29165404/benefits-of-nut-consumption-on-insulin-resistance-and-cardiovascular-risk-factors-multiple-potential-mechanisms-of-actions
#6
REVIEW
Yoona Kim, Jennifer B Keogh, Peter M Clifton
Epidemiological and clinical studies have indicated that nut consumption could be a healthy dietary strategy to prevent and treat type 2 diabetes (T2DM) and related cardiovascular disease (CVD). The objective of this review is to examine the potential mechanisms of action of nuts addressing effects on glycemic control, weight management, energy balance, appetite, gut microbiota modification, lipid metabolism, oxidative stress, inflammation, endothelial function and blood pressure with a focus on data from both animal and human studies...
November 22, 2017: Nutrients
https://www.readbyqxmd.com/read/29164519/atorvastatin-prevents-early-oxidative-events-and-modulates-inflammatory-mediators-in-the-striatum-following-intranasal-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-mptp-administration-in-rats
#7
Naiani F Marques, Adalberto A Castro, Gianni Mancini, Fernanda L Rocha, Adair R S Santos, Rui D Prediger, Andreza Fabro De Bem, Carla I Tasca
Atorvastatin is a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor with cholesterol-lowering, anti-inflammatory, and antioxidant properties. Increasing evidence show atorvastatin acts as a protective agent against insults in the central nervous system (CNS). The regular use of statins has been associated with a reduced risk of Parkinson's disease (PD) development. Here, we evaluated early events involved in the neurotoxicity induced by intranasal (i.n.) infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in rats and the potential of atorvastatin to prevent these early toxic events...
November 21, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29162465/linoleic-acid-enhance-the-production-of-moncolin-k-and-red-pigments-in-monascus-ruber-by-activating-mokh-and-moka-and-by-accelerating-camp-pka-pathway
#8
Jing Huang, NanQing Liao, HaoMing Li
Monacolin K, an inhibitor of HMG-CoA reductase, is a secondary metabolite synthesized by polyketide synthases (PKS) from Monascus ruber. The mokH gene encoding Zn(II)2Cys6 binding protein and mokA gene encoding polyketide synthase are presumed to activate monacolin K production. In this study, linoleic acid could be a quorum sensing signaling molecule to increase monacolin K production in the cyclic AMP(cAMP)-protein kinase A(PKA) signaling pathway. Analysis of the PKA activity and the cAMP concentration shows that linoleic acid could increase cAMP concentration and activate PKA...
November 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29158265/topical-mevastatin-promotes-wound-healing-by-inhibiting-the-transcription-factor-c-myc-via-the-glucocorticoid-receptor-and-the-long-noncoding-rna-gas5
#9
Andrew P Sawaya, Irena Pastar, Olivera Stojadinovic, Sonja Lazovic, Stephen C Davis, Joel Gil, Robert S Kirsner, Marjana Tomic-Canic
Diabetic foot ulcers (DFU), a life-threatening complication of diabetes mellitus, have limited treatment options, often resulting in amputations. HMG-CoA reductase inhibitors such as statins are cholesterol-reducing agents that may provide a new therapeutic option. Statins target the cholesterol pathway and block the synthesis of the wound-healing inhibitors farnesyl pyrophosphate (FPP) and cortisol, ligands for the glucocorticoid receptor (GR). Here we demonstrate that the naturally occurring statin, mevastatin, reverses FPP's effects and promotes healing by using in vitro wound healing assays, human ex vivo and porcine in vivo wound models, and DFU tissue...
November 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29155848/an-electronic-health-record-based-model-predicts-statin-adherence-ldl-cholesterol-and-cardiovascular-disease-in-the-united-states-military-health-system
#10
Joseph E Lucas, Taylor C Bazemore, Celan Alo, Patrick B Monahan, Deepak Voora
HMG-CoA reductase inhibitors (or "statins") are important and commonly used medications to lower cholesterol and prevent cardiovascular disease. Nearly half of patients stop taking statin medications one year after they are prescribed leading to higher cholesterol, increased cardiovascular risk, and costs due to excess hospitalizations. Identifying which patients are at highest risk for not adhering to long-term statin therapy is an important step towards individualizing interventions to improve adherence. Electronic health records (EHR) are an increasingly common source of data that are challenging to analyze but have potential for generating more accurate predictions of disease risk...
2017: PloS One
https://www.readbyqxmd.com/read/29151274/effect-of-hmg-coa-reductase-inhibitors-on-the-development-of-chronic-lung-allograft-dysfunction
#11
Amanda Szczepanik, Amanda Hulbert, Hui-Jie Lee, Clark Benedetti, Laurie Snyder, Jennifer Byrns
Lung transplant recipients (LR) have a reduced median five-year survival of approximately 55% primarily due to chronic lung allograft dysfunction (CLAD). Statins have anti-inflammatory and immunomodulatory effects that may facilitate CLAD prevention. This study sought to evaluate statin effect on CLAD development. Adult bilateral LR from January 2004-October 2013 were included. Statin group included recipients with early statin use and continued for minimum 6 months. Propensity score matching was performed for age, gender and native lung disease to select matched non-statin group...
November 19, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/29150805/aspergillus-terreus-treated-rice-straw-suppresses-methane-production-and-enhances-feed-digestibility-in-goats
#12
P Mohd Azlan, M F Jahromi, M O Ariff, M Ebrahimi, S C L Candyrine, J B Liang
The objectives of this study were to test the efficacy of producing lovastatin in rice straw treated with Aspergillus terreus in larger laboratory scale following the procedure previously reported and to investigate the effectiveness of the treated rice straw containing lovastatin on methane mitigation in goats. The concentration of lovastatin in the treated rice straw was 0.69 ± 0.05 g/kg dry matter (DM) rice straw. Our results showed that supplementation of lovastatin at 4.14 mg/kg BW reduced methane production by 32% while improving the DM digestibility by 13% (P < 0...
November 17, 2017: Tropical Animal Health and Production
https://www.readbyqxmd.com/read/29147490/hypolipidemic-effects-of-total-flavonoide-extracted-from-the-leaves-of-actinidiakolomikta-in-rats-fed-a-high-fat-diet
#13
Zhenxiang Yu, Huali Xu, Xiaofeng Yu, Dayun Sui, Guangzhu Lin
Objectives: This study was to investigate the antihyperlipidemic and antioxidant effect of total flavonoid extract from Actinidiakolomikta (TFAK) in hyperlipidemia induced by a high-fat diet. Materials and Methods: Male SD rats were randomly divided into 6 groups: normal group, model (hyperlipidemic diet) group, hyperlipedemic diet supplemented with TFAK (50, 100 and 200 mg/kg) and simvastatin (30 mg/kg) groups. The rats were administrated TFAK by oral for 28 days...
October 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29139594/a-multi-perspective-approach-to-solvent-regulation-of-enzymatic-activity-hmg-coa-reductase
#14
Frank Schulz, Michael Dirkmann, Javier Iglesias, Victor Muñoz, Pandian Sokkar, Christoph Rumancev, Andreas von Gundlach, Oktavian Krenczyk, Tobias Vöpel, Julia Nowack, Martin A Schroer, Simon Ebbinghaus, Christian Herrmann, Axel Rosenhahn, Elsa Sanchez-Garcia
HMG-CoA reductase was investigated in different organic co-solvents using kinetic and calorimetric measurements, molecular dynamics simulations and small-angle x-ray scattering. The combined experimental and theoretical techniques were essential to complement each other's limitations in the investigation of the complex interaction pattern between the enzyme and the different solvent types and concentrations. In this way, we could elucidate the underlying mechanisms for the loss of enzyme activity in different water-miscible solvents...
November 15, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29132077/lovastatin-analogues-and-other-metabolites-from-soil-derived-aspergillus-terreus-yim-ph30711
#15
Qiang Wang, Ya-Bin Yang, Xue-Qiong Yang, Cui-Ping Miao, Yi-Qing Li, Shi-Xi Liu, Na Luo, Zhong-Tao Ding, Li-Xing Zhao
Eight previously undescribed metabolites including of lovastatin analogues, a pair of diastereoisomers, a cyclopentenone dimer, and three polyketides were isolated from the culture of Aspergillus terreus YIM PH30711. Two types of unprecedented skeletons, benzene-cyclopentanone complex and linear polyketide, and an unusual dimer structure were determined by spectral analysis. Compound, 3α-hydroxy-3,5-dihydromonacolin L showed moderate activity against HMG-CoA reductase, with an inhibition ratio of 34% at the concentration of 50 μM, while lovastatin and dihydromonacolin K ethyl ester presented much stronger activity against HMGR with inhibition rates of 85% and 90% at the concentration of 50 μM, respectively...
November 10, 2017: Phytochemistry
https://www.readbyqxmd.com/read/29131001/atorvastatin-calcium-inhibits-pdgf-%C3%AE-%C3%AE-induced-proliferation-and-migration-of-vsmcs-through-the-g0-g1-cell-cycle-arrest-and-suppression-of-activated-pdgfr%C3%AE-pi3k-akt-signaling-cascade
#16
Shuang Chen, Siyuan Dong, Zhao Li, Xiaofan Guo, Naijin Zhang, Bo Yu, Yingxian Sun
BACKGROUND/AIMS: Abnormal proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of vascular lesions, such as atherosclerosis and restenosis. PDGF-ββ, an isoform of PDGF (platelet-derived growth factor), has been demonstrated to induce proliferation and migration of VSMCs. Atorvastatin calcium, a selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, has favorable protective effects on VSMCs. This study examined the effects of atorvastatin calcium on the proliferation and migration of PDGF-ββ-treated VSMCs, as well as its underlying mechanisms...
November 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29107682/underlying-mechanisms-for-sterol-induced-ubiquitination-and-er-associated-degradation-of-hmg-coa-reductase
#17
REVIEW
Brittany M Johnson, Russell A DeBose-Boyd
Accelerated ubiquitination and subsequent endoplasmic reticulum (ER)-associated degradation (ERAD) constitute one of several mechanisms for feedback control of HMG CoA reductase, the rate-limiting enzyme in synthesis of cholesterol and nonsterol isoprenoids. This ERAD is initiated by the accumulation of certain sterols in ER membranes, which trigger binding of reductase to ER membrane proteins called Insigs. Insig-associated ubiquitin ligases facilitate ubiquitination of reductase, marking the enzyme for extraction across the ER membrane through a reaction that is augmented by nonsterol isoprenoids...
October 28, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29103328/skin-cancer-associated-with-commonly-prescribed-drugs-tumor-necrosis-factor-alpha-inhibitors-tnf-%C3%AE-is-angiotensin-receptor-blockers-arbs-phosphodiesterase-type-5-inhibitors-pde5is-and-statins-weighing-the-evidence
#18
Beatrice Nardone, Kelsey A Orrell, Paras P Vakharia, Dennis P West
Skin cancers, including both malignant melanoma (MM) and nonmelanoma skin cancer (NMSC), are the most commonly diagnosed cancers in the US. The incidence of both MM and NMSC continues to rise. Areas Covered: Current evidence for an association between four of the most commonly prescribed classes of drugs in the U.S. and risk for MM and NMSC is reported. Medline was searched (January 2000 to May 2017) for each drug in the classes and for "basal cell carcinoma", "squamous cell carcinoma", "non-melanoma skin cancer", "skin cancer" and "melanoma"...
November 6, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29096742/hmgcr-and-apoe-mutations-may-cause-different-responses-to-lipid-lowering-statin-therapy
#19
D Kirac, E Bayam, M Dagdelen, H Gezmis, S Sarikaya, S Pala, E C Altunok, E Genc
Coronary artery disease (CAD) and its complications are the major causes of death in the world. Although statins have been used to lower lipid levels in CAD patients, this goal can not be attained in 1/3 of the patients. The objective of this study was to investigate whether common variations in HMG-CoA Reductase(HMGCR) and Apolipoprotein E (ApoE) genes involved in lipid and statin metabolism modify the effect of statins on serum lipid and lipoprotein concentrations in CAD patients.A hundred  CAD patients were enrolled into the study...
October 31, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/29095667/pcsk9-inhibitors-mechanisms-of-action-metabolic-effects-and-clinical-outcomes
#20
Connie N Hess, Cecilia C Low Wang, William R Hiatt
Atherosclerotic cardiovascular disease (ASCVD) is associated with significant morbidity and mortality worldwide. Increased serum levels of lowdensity lipoprotein cholesterol (LDL-C) are an independent risk factor for ASCVD, and clinical trial data have shown that lowering LDL-C generally reduces cardiovascular risk. Until recently, 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase inhibitors (statins) have been the main therapy for lowering LDL-C. However, some statin-treated patients have persistently elevated residual cardiovascular risk due to inadequate lowering of LDL-C levels or non-LDL-related dyslipidemia...
November 2, 2017: Annual Review of Medicine
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