cholesterol synthesis

Simvastatin (MK 733) is an HMG-CoA reductase inhibitor (Ki=0.2 nM) with oral activity. Simvastatin has hypolipidemic activity, inhibits hepatic production of cholesterol, and is also used for the prevention of cardiovascular disease.

Lathosterol, a molecule akin to cholesterol, serves as a biomarker for the body's total cholesterol synthesis, as indicated by its serum concentration.

Cholesterol (cholesteryl alcohol) is a natural product that is the major sterol in mammals and an agonist of estrogen-related receptor α (ERRα). Cholesterol is widely found in the cell membranes of animals and is also used in the synthesis of several important hormones and bile acids.

Squalene (AddaVax) is a natural organic compound originally obtained for commercial purposes primarily from shark liver oil, though there are botanical sources as well, including rice bran, wheat germ, and olives. All higher organisms produce squalene, including humans. Squalene is an intermediate product in the synthesis of cholesterol and shows several pharmacological properties such as hypolipidemic, hepatoprotective, cardioprotective, antioxidant, and antitoxicant activity.

3-Hydroxybutyric acid (Butanoic acid) (or beta-hydroxybutyrate) is a ketone body. Like the other ketone bodies (acetoacetate and acetone), levels of 3-hydroxybutyrate in blood and urine are raised in ketosis. In humans, 3-hydroxybutyrate is synthesized in the liver from acetyl-CoA and can be used as an energy source by the brain when blood glucose is low. Blood levels of 3-hydroxybutyric acid levels may be monitored in diabetic patients to look for diabetic ketoacidosis. Persistent mild hyperketonemia is a common finding in newborns. Ketone bodies serve as an indispensable source of energy for extrahepatic tissues, especially the brain and lung of developing mammals. Another important function of ketone bodies is to provide acetoacetyl-CoA and acetyl-CoA for the synthesis of cholesterol, fatty acids, and complex lipids. During the early postnatal period, acetoacetate (AcAc) and beta-hydroxybutyrate are preferred over glucose as substrates for synthesis of phospholipids and sphingolipids in accord with requirements for brain growth and myelination. Thus, during the first 2 weeks of postnatal development, when the accumulation of cholesterol and phospholipids accelerates, the proportion of ketone bodies incorporated into these lipids increases. On the other hand, an increased proportion of ketone bodies is utilized for cerebroside synthesis during the period of active myelination. In the lung, AcAc serves better than glucose as a precursor for the synthesis of lung phospholipids. The synthesized lipids, particularly dipalmitoylphosphatidylcholine, are incorporated into surfactant, and thus have a potential role in supplying adequate surfactant lipids to maintain lung function during the early days of life (PMID: 3884391 ). 3-Hydroxybutyric acid is found to be associated with fumarase deficiency and medium-chain acyl-CoA dehydrogenase deficiency, which are inborn errors of metabolism.

D-Pantothenic acid (vitamin B5) is a water-soluble vitamin ubiquitously found in plants and animal tissues with an antioxidant property. D-Pantothenic acid is a component of coenzyme A (CoA) and a part of the vitamin B2 complex. D-Pantothenic acid is a growth factor and is essential for various metabolic functions, including the metabolism of carbohydrates, proteins, and fatty acids. This vitamin is also involved in the synthesis of cholesterol, lipids, neurotransmitters, steroid hormones, and hemoglobin.

Uridine 5'-monophosphate disodium salt (Disodium UMP) has been used to study the effect of pyrimidine synthesis inhibitor, 5-azacytidine, on cholesterol and lipid metabolism. It has been used to study the effect of nucleotides on growth of specific intestinal bacteria.

Lanosterol (3β-Hydroxy-8,24-lanostadiene) is a tetracyclic triterpenoid which is the compound from which all steroids are derived.

7α-Hydroxy-4-cholesten-3-one is an intermediate in bile acid synthesis from cholesterol, a PXR agonist, and a biomarker for bile acid loss and diseases related to defective bile acid biosynthesis. It is also the physiological substrate for [CYP8B1].

Mevalonic acid lithium salt (MVA lithium salt) is a precursor of the mevalonic acid pathway, an initiator of cell growth, a key substance in cholesterol synthesis, and stimulates DNA synthesis, morphology transformation, and cell cycling in human lymphocytes from peripheral blood.

Beauveriolide I is a cyclodepsipeptide that has been found inBeauveriaand an inhibitor of lipid droplet formation.1It inhibits lipid droplet formation when used at concentrations of 3 and 10 μM, as well as inhibits cholesterol synthesis (IC50= 0.78 μM), in primary mouse peritoneal macrophages.1,2Beauveriolide I also inhibits acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in mouse macrophage membranes (IC50= 6 μM).2 1.Namatame, I., Tomoda, H., Si, S., et al.Beauveriolides, specific inhibitors of lipid droplet formation in mouse macrophages, produced by Beauveria sp. FO-6979J. Antibiot. (Tokyo)52(1)1-6(1999) 2.Namatame, I., Tomoda, H., Ishibashi, S., et al.Antiatherogenic activity of fungal beauveriolides, inhibitors of lipid droplet accumulation in macrophagesProc. Nat. Acad. Sci. USA101(3)737-742(2004)

Beauveriolide III is a cyclodepsipeptide that has been found inBeauveriaand an inhibitor of lipid droplet formation.1It inhibits lipid droplet formation when used at concentrations of 3 and 10 μM, as well as inhibits cholesterol synthesis (IC50= 0.41 μM), in primary mouse peritoneal macrophages.1,2Beauveriolide III also inhibits acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in mouse macrophage membranes (IC50= 5.5 μM).2Beauveriolide III (25 and 50 mg/kg) reduces the size of aortic atherosclerotic lesions inLdlr-/-andApoE-/-mouse models of atherosclerosis. 1.Namatame, I., Tomoda, H., Si, S., et al.Beauveriolides, specific inhibitors of lipid droplet formation in mouse macrophages, produced by Beauveria sp. FO-6979J. Antibiot. (Tokyo)52(1)1-6(1999) 2.Namatame, I., Tomoda, H., Ishibashi, S., et al.Antiatherogenic activity of fungal beauveriolides, inhibitors of lipid droplet accumulation in macrophagesProc. Nat. Acad. Sci. USA101(3)737-742(2004)

1. Coptisine (Coptisin) treatment increases cell viability based on its reversal effect on the enhanced activity of Indoleamine 2, 3-dioxygenase . 2. Coptisine treats myocardial I R likely through suppressing myocardial apoptosis and inflammation by inhibiting the Rho ROCK pathway. 3. Coptisine is a potential anti-osteosarcoma drug candidate, via exerting a strong anti-osteosarcoma effect with very low toxicity . 4. Coptisine with a high dosage could inhibit cholesterol synthesis via suppressing the HMGCR expression and promoting the use and excretion of cholesterol via up-regulating LDLR and CYP7A1 expression. 5. Coptisine suppresses adhesion, migration and invasion of MDA-MB-231 breast cancer cells in vitro, the down-regulation of MMP-9 in combination with the increase of TIMP-1 possibly contributing to the anti-metastatic function for breast cancer.

Agistatin B, a mycotoxin isolated from fungus, inhibits cholesterol synthesis [1].

1. Homogentisic acid (2,5-dihydroxyphenylacetic acid) shows interesting antioxidant and antiradical activities, and protective effect against thermal-cholesterol degradation, comparable to those of well known antioxidants. 2. Homogentisic acid is the primary precursor of melanin synthesis in Vibrio cholerae, a Hyphomonas strain, and Shewanella colwelliana. 3. A derivative of homogentisic acid which inhibits Pfnek-1 with an IC(5) around 1.8 muM, this product is moderately active in vitro against a FcB1 P. falciparum strain (IC(5) = 12 muM).

(-)-Hydroxycitric acid (HCA) can inhibit fat synthesis and reduces food intake, the primary mechanism of action of HCA appears to be related to its ability to act as a competitive inhibitor of the enzyme ATP-citrate lyase, which catalyzes the conversion of citrate and coenzyme A to oxaloacetate and acetyl coenzyme A (acetyl-CoA), primary building blocks of fatty acid and cholesterol synthesis.

Helminthosporol is a natural plant growth regulator that promotes the growth of rice and lettuce seedlings. It also inhibits the activity of acyl-CoA:cholesterol acyltransferase (ACAT) in rat liver microsomes and the synthesis of cholesterol esters in macrophages.