Feedback Control of Mevalonate Synthesis by Dietary Cholesterol

Siperstein, Marvin D.; Fagan, Violet M.

doi:10.1016/s0021-9258(18)96879-1

Cited by 311 publications

(21 citation statements)

References 31 publications

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“…It is a competitive inhibitor of HMG-CoA reductase in bacterial systems (24), and the in vitro inhibition of microsomal HMG-CoA reductase from both liver and intestine has been shown (25). The enzymatic control of cholesterol biosynthesis is al-most exclusively at the HMG-CoA reductase step at which HMG-CoA is converted to mevalonic acid (26). From this earlier interest in HMG as a potential hypocholesterolemic agent, the acute toxicity was studied in mice (27).…”

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confidence: 99%

Identification of 3-Hydroxy-3-methylglutaric Acid (HMG) as a Hypoglycemic Principle of Spanish Moss (Tillandsia usneoides)

Witherup¹,

McLaughlin²,

Judd³

et al. 1995

J. Nat. Prod.

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Bioactivity-directed fractionation, using brine shrimp lethality and murine hypoglycemia, of an ethanol extract prepared from Tillandsia usneoides, led to the isolation of four apparently bioactive compounds from the water-soluble fraction. The compounds were identified as citric acid, succinic acid, 3-hydroxy-3-methylglutaric acid (HMG), and 3,6,3',5'-tetramethoxy-5,7,4'-trihydroxyflavone-7-O-beta-D-g lucoside. The brine shrimp lethality of the acids was simply due to acidity; however, HMG elicited significant hypoglycemic responses in fasting normal mice. Ethyl and methyl esters of citric acid were prepared and tested in the murine hypoglycemic assay. Five of the predominant sugars were identified by tlc. Free thymidine was also isolated. Further evaluation of HMG and other potential inhibitors of HMG CoA lyase, in the treatment of symptoms of diabetes mellitus, is suggested.

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confidence: 99%

Identification of 3-Hydroxy-3-methylglutaric Acid (HMG) as a Hypoglycemic Principle of Spanish Moss (Tillandsia usneoides)

Witherup¹,

McLaughlin²,

Judd³

et al. 1995

J. Nat. Prod.

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“…A thiol requirement for enzyme activity has been previously observed with regard to this enzyme (Durr and Rudney, 1960;Knappe et al, 1959;Siperstein and Fagan, 1966;Kirtley and Rudney, 1967). The activity of the microsomal suspension was doubled by the addition of 100 pM dithiothreitol.…”

Section: Resultsmentioning

confidence: 69%

Solubilization and purification of β-hydroxy-β-methylglutaryl coenzyme A reductase from rat liver

Kawachi¹,

Rudney²

1970

Biochemistry

103

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“…The established role of mevalonate in the sterolgenic pathway (Brown and Goldstein, 1980) coupled with the renewed interest in the unique regulation of its synthesis in neoplastic tissue (Siperstein and Fagan, 1964) led us to develop a microbiological assay for screening plant materials for constituents that might act as dietary suppressors of mevalonate biosynthesis. The assay appears to detect in test materials the presence of non-sterol, postmevalonate products that suppress mevalonate synthesis.…”

Section: Discussionmentioning

confidence: 99%