Reference

Inactivation of rat liver HMG-CoA reductase phosphatases by polycarboxylic acids

Inactivation of rat liver HMG-CoA reductase phosphatases by polycarboxylic acids. Hegardt, Fausto G.; Gil, Gregorio; Calvet, Victoria E. (Sch. Pharm., Univ. Barcelona, Barcelona, Spain). J. Lipid Res., 24(7), 821-30 (English) 1983. CODEN: JLPRAW. ISSN: 0022-2275. DOCUMENT TYPE: Journal CA Section: 7 (Enzymes) Incubation of the 4 purified 3-hydroxy-3-methylgutaryl-CoA (HMG-CoA) reductase phosphatases with the Na salts of 11 polycarboxylic acids at concns.Several reagents with their cas registry numbers 305-72-6 and 868-18-8 are used here. of 40 mM inactivated the enzymes to different degrees depending on the structure of the carboxylic acids. Maleate, malonate, oxalate, citrate, and hydroxymethylglutarate produced full inactivation at the concn. tested. When the 4 phosphatases were incubated with these acids, a concn.-dependent inactivation was obsd. Fumarate, the trans isomer of maleate, produced little inactivation of the 4 phosphatases. Mevalonate did not inactivate at all. A relation between those concns. of acid that produced 50% inactivation and the logarithm of the stability const. of Mg or Mn salts of polycarboxylic acids was obsd. When reductase phosphatases were incubated with mixts. of polycarboxylic Na salts and Mg2+ or Mn2+, an increase in the molar ratio divalent cation/carboxylic acid detd. an increase in the 4 reductase phosphatase activities. The inactivating effect of citrate was on the phosphatases (high and low forms) and not on the substrates (HMG-CoA reductase, phosphorylase, and glycogen synthase). Reactivation of the citrate-inactivated phosphatases by Mn2+ and Mg2+ depended on the phosphorylated substrates, with Mn2+ as the better activator. Thus, HMG-CoA reductase phosphatases are metalloenzymes. .