3-Hydroxy-3-methylglutarate

Three other portions of the molecule which do not fit the polyketide combination pattern (Scheme 7B a,f,n) can be also explained by assuming they are derived from a dicarboxylic acid such as 3-hydroxy-3-methylglutaric acid (Scheme 8b). If that is the case, brevetoxins are a new type of mbced polyketides which are formed by condensation on both ends of dicarboxylic acids (Scheme 8c). In order to prove further the hypothesis, feeding experiments with such putative precursors as succinate, acetoacetate, and propionate are in progress. 

Hydroxy-3-methylglutaric acid [503-49-1] M 162.1, m 99-102 . Recrystd from ethyl ether/hexane and dried under vac at 60° for 1 h. 

Individuals who are deficient in HMG-CoA lyase are unable to complete the metabolism of leucine. The increased urinary excretion of 3-hydroxy-3-methylglutaric acids is the primary biochemical criterion that distinguishes this particular enzymatic defect from other defects in enzymes of leucine catabolism that also result in metabolic acidosis and abnormal organic aciduria. There is also substantial urinary excretion of intermediates of leucine catabolism, such as 3-methylglutaconic acid, and their metabolites, including 3-hydroxy-isovaleric acid produced from isovaleric acid. 

Carnitine deficiency complicates HMG-CoA lyase deficiency and other inborn errors of metabolism, which results in organic acidemia. L-Camitine or P-hydroxy-y-trimethylammonium butyrate is a carrier molecule that transports long-chain fatty acids across the inner mitochondrial membrane for subsequent P-oxi-dation. L-Carnitine also facilitates removal of toxic metabolic intermediates or xenobiotics via urinary excretion of their acyl carnitine derivatives. Indeed, individuals with HMG-CoA lyase deficiency have been shown to excrete 3-methylgluatarylcamitine (Roe et al., 1986). In the absence of ketogenesis, the formation of the acyl carnitine derivative of 3-hydroxy-3-methylglutarate from HMG-CoA also serves to regenerate free CoA in the mitochondria and permits continued P-oxidation of fatty acids. 

Cyclopentanoid Monoterpenoids.—Further studies confirm that mevalonic acid, but not 3-hydroxy-3-methylglutaric acid, is specifically incorporated into loganic acid (27), and methionine or adenosylmethionine into loganin (28). The latter metabolite is a key intermediate in indole alkaloid biosynthesis. ... 

The oral administration of 3-hydroxy-3-methylglutaric acid (HMG) prevented the alcohol-induced postprandial elevation of serum lipids and 3-lipoproteins in man.102 CL-719 (17) produced a dose-dependent suppression... 

Beg, Z.H. Stonik, J.A. Brewer, B. Human hepatic 3-hydroxy-3-methylglutar-yl coenzyme A reductase evidence for the regulation of enzymic activity by a bicyclic phosphorylation cascade. Biochem. Biophys. Res. Commun., 119, 488-498 (1984)... 

C-0 bound rutinose (26) and 3-hydroxy-3-methylglutaric acid (28), respectively, at C-3 exhibit weak hypotensive effects. Also compounds (29, 30, and 31) having 3-hydroxy-3-methylglutaric acid at C-3 exhibit weak hypotensive effects. Narcissin (32), however, does not exhibit any hypotensive effect. 

Isovaleric acidemia Glutaric acidemia type II 3-Hydroxy-3-methylglutaric aciduria... 

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