Journal of Lipid Research, Vol 24, 821-830, Copyright © 1983 by Lipid Research, Inc.
Inactivation of rat liver HMG-CoA reductase phosphatases by polycarboxylic acids
FG Hegardt, G Gil and VE Calvet
Incubation of the four purified HMG-CoA reductase phosphatases with the
sodium salts of eleven polycarboxylic acids at concentrations 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 concentration
tested. When the four phosphatases were incubated with these acids, a
concentration-dependent inactivation was observed. Fumarate, the trans
isomer of maleate, produced little inactivation of the four phosphatases.
Mevalonate did not inactivate at all. A relationship between those
concentrations of acid that produced a 50% inactivation and the logarithm
of the stability constant of Mg2+ or Mn2+ salts of polycarboxylic acids was
observed. When reductase phosphatases were incubated with mixtures of
polycarboxylic sodium salts and Mg2+ or Mn2+, an increase in the molar
ratio divalent cation/carboxylic acid determined an increase in the four
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, Mn2+ being the better activator. It is concluded
that HMG- CoA reductase phosphatases are metalloenzymes.
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