Statins regulation

Statins, release inhibiting factors, release inhibiting hormones, neurohormones synthesized in the small-cell region of the hypothalamus and transported via the bloodstream to the anterior pituitary. Members of the statins include melanostatin, somatostatin, and prolactostatin. They inhibit the secretion of melanotropin, somatotropin, and prolactin, respectively. Together with the corresponding liberins, the statins regulate the levels of the three pituitary hormones. 

The lipid regulator drugs bezafibrate and fenofibrate at initial concentrations of 4.5 and 4.2 ng g-1 in sterile sludge were completely removed after the fungal treatment. The fate of fenofibrate, also present in non-sterile sludge, was the same. Meanwhile, the most abundant atorvastatin, a cholesterol lowering statin, decreased its concentration in 80% and 65% in sterile and non-sterile conditions, respectively. 

Activators and inhibitors regulate not the amount of enzyme protein but the activity ( efficiency ) of that which is present. Two principal mechanisms of control are (i) competitive and (ii) allosteric. Competitive control (inhibition) occurs when a compound which is structurally similar to the true substrate binds to the active site of the enzyme. This is how a number of drugs and poisons bring about their effect. For example, a group of therapeutic drugs called statins are used to treat heart disease because by inhibiting a key enzyme called HMGCoA reductase, they reduce the hepatic synthesis of cholesterol and therefore the plasma concentration of that lipid. 

Rhabdomyolysis is the destruction of skeletal muscle tissues and may be associated with lipid-regulating drugs such as the fibrates and the statins. The risk of this side-effect is increased in patients with renal impairment and with hypothyroidism. Rhabdomyolysis may also occur with nicotinic acid, the antipsychotic aripiprazole, and the anaesthetic propofol. 

The lowered concentration of bile acids returning to the liver by the enterohepatic circulation results in derepression of 7-a-hydroxylase, the rate-limiting enzyme for conversion of cholesterol to bile acids. This results in increased use of cholesterol to replace the excreted bile acids and lowering of hepatic cholesterol (mechanism VI in Fig. 23.2). Thus, similar to the statins, the ultimate actions of the bile acid-sequestering resins are up-regulation of transcription of the LDL receptor gene, increased hepatic receptor activity, and lowering of plasma LDL cholesterol (mechanism VII in Fig. 23.2). 

Sheperd J. The statin era in search of the ideal lipid regulating agent. Heart, 2001, 85, 259-264. 

Synthetic statins are important lipid regulating drugs for the treatment of atherosclerosis and other diseases related to hyperlipidaemia, especially coronary heart disease. As the pharmacophore, all synthetic statins contain a saturated or partially unsaturated syn-3,5-dihydroxy C7-carboxylate. An important building block for the synthesis of the side chain is represented by 4-chloro-3-hydroxybutanoate esters (CHBE). Both enantiomers can be obtained by enzyme-catalyzed reduction of the (1-keto ester. The group of Kataoka and Shimizu found that an aldehyde reductase of Sporobolomyces salmonicolor [161] and a carbonyl reductase of Candida... 

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