Reaction: ATP + [hydroxymethylglutaryl-CoA reductase (NADPH)] = ADP + [hydroxymethylglutaryl-CoA reductase (NADPH)] phosphate
For diagram click here.
Other name(s): AMPK; AMP-activated protein kinase; HMG-CoA reductase kinase; β-hydroxy-β-methylglutaryl-CoA reductase kinase; [hydroxymethylglutaryl-CoA reductase (NADPH2)] kinase; 3-hydroxy-3-methylglutaryl coenzyme A reductase kinase; 3-hydroxy-3-methylglutaryl-CoA reductase kinase; hydroxymethylglutaryl coenzyme A reductase kinase; hydroxymethylglutaryl coenzyme A reductase kinase (phosphorylating); hydroxymethylglutaryl-CoA reductase kinase; reductase kinase; STK29
Systematic name: ATP:[hydroxymethylglutaryl-CoA reductase (NADPH)] phosphotransferase
Comments: The enzyme is activated by AMP. EC 1.1.1.34, hydroxymethylglutaryl-CoA reductase (NADPH) is inactivated by the phosphorylation of the enzyme protein. Histones can also act as acceptors. The enzyme can also phosphorylate hepatic acetyl-CoA carboxylase (EC 6.4.1.2) and adipose hormone-sensitive lipase (EC 3.1.1.79) [5]. Thr-172 within the catalytic subunit (α-subunit) is the major site phosphorylated by the AMP-activated protein kinase kinase [7]. GTP can act instead of ATP [4]
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 172522-01-9
References:
1. Beg, Z.H., Stonik, J.A. and Brewer, H.B., Jr. 3-Hydroxy-3-methylglutaryl coenzyme A reductase: regulation of enzymatic activity by phosphorylation and dephosphorylation. Proc. Natl. Acad. Sci. USA 75 (1978) 3678-3682. [PMID: 278983]
2. Gibson, D.M. and Ingebritsen, T.S. Reversible modulation of liver hydroxymethylglutaryl CoA reductase. Life Sci. 23 (1978) 2649-2664. [PMID: 216867]
3. Ingebritsen, T.S., Lee, H.-S., Parker, R.A. and Gibson, D.M. Reversible modulation of the activities of both liver microsomal hydroxymethylglutaryl coenzyme A reductase and its inactivating enzyme. Evidence for regulation by phosphorylation-dephosphorylation. Biochem. Biophys. Res. Commun. 81 (1978) 1268-1277. [PMID: 666819]
4. Ferrer, A., Caelles, C., Massot, N. and Hegardt, F.G. Allosteric activation of rat liver microsomal [hydroxymethylglutaryl-CoA reductase (NADPH)]kinase by nucleoside phosphates. Biol. Chem. Hoppe Seyler 368 (1987) 249-257. [PMID: 3689494]
5. Weekes, J., Ball, K.L., Caudwell, F.B. and Hardie, D.G. Specificity determinants for the AMP-activated protein kinase and its plant homologue analysed using synthetic peptides. FEBS Lett. 334 (1993) 335-339. [PMID: 7902296]
6. Crute, B.E., Seefeld, K., Gamble, J., Kemp, B.E. and Witters, L.A. Functional domains of the a1 catalytic subunit of the AMP-activated protein kinase. J. Biol. Chem. 273 (1998) 35347-35354. [PMID: 9857077]
7. Stein, S.C., Woods, A., Jones, N.A., Davison, M.D. and Carling, D. The regulation of AMP-activated protein kinase by phosphorylation. Biochem. J. 345 (2000) 437-443. [PMID: 10642499]