HMGR3-Hydroxy-3-Methylglutaryl-CoA Reductase (enzyme)
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The results of real-time PCR showed that over- expression of SSBP1 inhibited the expression of LDLR and SCARB, while knockdown of SSBP1 significantly promoted the mRNA expression of LDLR, HMGR, CETP and SCARB.
Abbreviations: LDL, low-density lipoprotein; oxLDL, oxidized low-density lipoprotein; ASA, acetylsalicylic acid; COX, cyclooxygenase; PCI, prostaglandin; LX, lipoxin; TNFar, tumor necrosis factor-alpha; IL, interleukin; NFrcB, nuclear factor kappa B; ROS, reactive oxygen species; HMGr, 3-hydroxy-3-methyl-glutaryl-CoA reductase; LDLr-KO, knockout for the low-density lipoprotein receptor; IFN-y, interferon gamma; 15RHETH, 15R-hydroxyeicosatetraenoic acid; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; HPLC.
A key enzyme involved in this pathway is 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), which catalyzes the production of mevalonate.
Therefore, the present study was designed to investigate the expression of key enzymes of mevalonate pathway in (1) aortas from streptozotocin- (STZ-) induced 0-, 8-, and 16-week diabetic mice in vivo and (2) high-glucose-induced proliferated VSMCs in vitro, including HMGR, FPPS, FNT-[beta], GGT-1[beta], squalene synthase (SQS), phosphor-3-hydroxy-3-methylglutaryl- coenzyme A reductase (P-HMGR), and geranylgeranyl pyrophosphate synthase (GGPPS) (Figure 1).
However biochemical characterization of purified or recombinant enzymes of the MVAP in insects is limited to HMGS [68], HMGR [69-71], IPPI [66, 67], and FPPS [60-65].
While CPR and HMGR transcripts were detected both in the control group and in the DHAA-treated group, the transcript abundances for these two groups appeared little different.
In contrast, geranyl pyrophosphate synthase (GPPS) and 3hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) showed minor down regulation in response to both As treatments (Figure 5).
(56), (57) Like statins, tocotrienols affect the HMGR pathway.
The statins differ with respect to their ring structure and these differences in structure affect the pharmacological properties of the statins, such as the affinity for the active site of the HMGR, rates of entry into hepatic and non-hepatic tissues, availability in the systemic circulation for uptake into non-hepatic tissues and routes and modes of metabolic transformation and elimination.
"The class of drugs most commonly used to lower cholesterol - statins - are the blockbusters of the pharmaceutical world and work by inhibiting HMGR," says Professor Brown.
SM is one of at least 20 enzymes involved in the assembly line when cholesterol is made throughout the body but only one -- HMG-CoA reductase (HMGR) - is currently targeted by medications to lower cholesterol levels in the blood.
(28) And in a remarkable finding, the activity of the cholesterol-producing enzyme HMG-CoA-reductase (HMGR) was significantly lower in both the resveratrol and the clofibrate group--a noteworthy finding, since reducing HMGR activity is the target of the widely prescribed lipid-lowering medications called statins.