Beta-hydroxy-beta-methylglutaryl coenzyme a hydrolase of rat liver
Beta-Hydroxy-beta-methylglutaryl coenzyme A hydrolase, or deacylase, (EC 3.1.2.5) is important, at least potentially, in the regulation of mammalian cholesterol synthesis. This is so for two reasons, both related to the enzyme generally regarded as rate-limiting for cholesterogenesis, namely beta-hy...
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| Format: | Article |
| Language: | English |
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Elsevier
1981
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| Online Access: | http://psasir.upm.edu.my/id/eprint/38811/ http://psasir.upm.edu.my/id/eprint/38811/1/a84%20-%20hydroxy%20methyglutar.pdf |
| _version_ | 1848848976732749824 |
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| author | Sipat, Abdullah Sabine, John R. |
| author_facet | Sipat, Abdullah Sabine, John R. |
| author_sort | Sipat, Abdullah |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Beta-Hydroxy-beta-methylglutaryl coenzyme A hydrolase, or deacylase, (EC 3.1.2.5) is important, at least potentially, in the regulation of mammalian cholesterol synthesis. This is so for two reasons, both related to the enzyme generally regarded as rate-limiting for cholesterogenesis, namely beta-hydroxy-beta-methylglutaryl CoA reductase: (i) the hydrolase competes for the same substrate as the reductase and (ii) its end product, hydroxymethylglutamic acid, is a known inhibitor of the reductase. Consequently we have examined some of the properties of the hydrolase, as found in rat liver, after first developing a simple isotopic technique for its assay. Beta-Hydroxy-beta-methylglutaryl CoA hydrolase is both soluble and microsomal. The microsomal enzyme is inactivated by pre-incubation at 37 degree C, but not a 4 degree C, has an apparent pH optimum of approximately 7.6, and has Km and V values of 270 (microM) and 33.3 (nmol HMG/10 per mg protein), respectively, at 37 degree C. For the cytosolic enzyme the corresponding Km and V values are 830 and 111.1. From our observations it seems unlikely that beta-hydroxy-beta-methylglutaryl CoA hydrolase plays a significant role in the regulation of hepatic cholesterol synthesis since, in contrast to microsomal beta-hydroxy-beta-methylglutaryl coenzyme A reductase, we could find for the microsomal hydrolase no evidence of a diurnal rhythm of activity, no inhibition of activity by short-term cholesterol feeding and no evidence from Arrhenius-plot data for any membrane-mediated control of enzyme activity. Thus, the significance of the enzyme in mammalian systems remains unknown. |
| first_indexed | 2025-11-15T09:43:03Z |
| format | Article |
| id | upm-38811 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T09:43:03Z |
| publishDate | 1981 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-388112015-06-10T00:26:27Z http://psasir.upm.edu.my/id/eprint/38811/ Beta-hydroxy-beta-methylglutaryl coenzyme a hydrolase of rat liver Sipat, Abdullah Sabine, John R. Beta-Hydroxy-beta-methylglutaryl coenzyme A hydrolase, or deacylase, (EC 3.1.2.5) is important, at least potentially, in the regulation of mammalian cholesterol synthesis. This is so for two reasons, both related to the enzyme generally regarded as rate-limiting for cholesterogenesis, namely beta-hydroxy-beta-methylglutaryl CoA reductase: (i) the hydrolase competes for the same substrate as the reductase and (ii) its end product, hydroxymethylglutamic acid, is a known inhibitor of the reductase. Consequently we have examined some of the properties of the hydrolase, as found in rat liver, after first developing a simple isotopic technique for its assay. Beta-Hydroxy-beta-methylglutaryl CoA hydrolase is both soluble and microsomal. The microsomal enzyme is inactivated by pre-incubation at 37 degree C, but not a 4 degree C, has an apparent pH optimum of approximately 7.6, and has Km and V values of 270 (microM) and 33.3 (nmol HMG/10 per mg protein), respectively, at 37 degree C. For the cytosolic enzyme the corresponding Km and V values are 830 and 111.1. From our observations it seems unlikely that beta-hydroxy-beta-methylglutaryl CoA hydrolase plays a significant role in the regulation of hepatic cholesterol synthesis since, in contrast to microsomal beta-hydroxy-beta-methylglutaryl coenzyme A reductase, we could find for the microsomal hydrolase no evidence of a diurnal rhythm of activity, no inhibition of activity by short-term cholesterol feeding and no evidence from Arrhenius-plot data for any membrane-mediated control of enzyme activity. Thus, the significance of the enzyme in mammalian systems remains unknown. Elsevier 1981-10-23 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/38811/1/a84%20-%20hydroxy%20methyglutar.pdf Sipat, Abdullah and Sabine, John R. (1981) Beta-hydroxy-beta-methylglutaryl coenzyme a hydrolase of rat liver. Biochimica et Biophysica Acta, 666 (1). pp. 181-190. ISSN 0304-4165; ESSN: 1872-8006 |
| spellingShingle | Sipat, Abdullah Sabine, John R. Beta-hydroxy-beta-methylglutaryl coenzyme a hydrolase of rat liver |
| title | Beta-hydroxy-beta-methylglutaryl coenzyme a hydrolase of rat liver |
| title_full | Beta-hydroxy-beta-methylglutaryl coenzyme a hydrolase of rat liver |
| title_fullStr | Beta-hydroxy-beta-methylglutaryl coenzyme a hydrolase of rat liver |
| title_full_unstemmed | Beta-hydroxy-beta-methylglutaryl coenzyme a hydrolase of rat liver |
| title_short | Beta-hydroxy-beta-methylglutaryl coenzyme a hydrolase of rat liver |
| title_sort | beta-hydroxy-beta-methylglutaryl coenzyme a hydrolase of rat liver |
| url | http://psasir.upm.edu.my/id/eprint/38811/ http://psasir.upm.edu.my/id/eprint/38811/1/a84%20-%20hydroxy%20methyglutar.pdf |