Is the reaction catalyzed by 3-hydroxy-3-methylglutaryl coenzyme A reductase a rate-limiting step for isoprenoid biosynthesis in plants?

• Published in: Plant physiology (Bethesda) Vol. 109; no. 4; pp. 1337 - 1343
• Main Authors: CHAPPELL, J, WOLF, F, PROULX, J, CUELLAR, R, SAUNDERS, C
• Format: Journal Article
• Language: English
• Published: Rockville, MD American Society of Plant Physiologists 01.12.1995
• Subjects: acide organique; acidos organicos; aciltransferasa; actividad enzimatica; activite enzymatique; acyltransferase; acyltransferases; adn recombinado; adn recombine; biochemical pathways; Biochemistry and Enzymology; Biological and medical sciences; biosintesis; biosynthese; Biosynthesis; Coenzymes; duracion; duration; duree; Enzyme activity; enzyme precursors; Enzymes; enzymic activity; esteroles; expresion genica; expression des genes; Fundamental and applied biological sciences. Psychology; gene expression; Leaves; lipide; lipidos; lipids; Metabolism; Metabolism. Physicochemical requirements; metabolite; metabolites; metabolitos; nicotiana tabacum; organic acids; oxidoreductases; oxidorreductasas; oxydoreductase; Plant physiology and development; plantas transgenicas; plante transgenique; Plants; precurseur d' enzyme; precursores de enzimas; recombinant dna; Sesquiterpenes; sterol; Sterols; Terpenoids; Transgenic plants; via bioquimica del metabolismo; voie biochimique du metabolisme; Agrobacterium tumefaciens; Gene overexpression; Biosynthesis; Nicotiana tabacum; Regulation(control); Enzymatic activity; Dicotyledones; Angiospermae; Bacteria; Chemical composition; Transgenic plant; Solanaceae; Secondary metabolism; Enzyme; Rodentia; Isoprenoid; Vertebrata; Mammalia; Hydroxymethylglutaryl-CoA reductase; Spermatophyta; Oxidoreductases; Rhizobiaceae; Biological accumulation; Hamster; Sterol
• ISSN: 0032-0889; 1532-2548
• DOI: 10.1104/pp.109.4.1337

3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) catalyzes the irreversible conversion of 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate and is considered a key regulatory step controlling isoprenoid metabolism in mammals and fungi. The rate-limiting nature of this enzyme for isoprenoid biosynthesis in plants remains controversial. To investigate whether HMGR activity could be limiting in plants, we introduced a constitutively expressing hamster HMGR gene into tobacco (Nicotiana tabacum L.) plants to obtain unregulated HMGR activity. The impact of the resulting enzyme activity on the biosynthesis and accumulation of particular isoprenoids was evaluated. Expression of the hamster HMGR gene led to a 3- to 6-fold increase in the total HMGR enzyme activity. Total sterol accumulation was consequently increased 3- to 10-fold, whereas end-product sterols such as sitosterol, campesterol, and stigmasterol were increased only 2-fold. The level of cycloartenol, a sterol biosynthetic intermediate, was increased more than 100-fold. Although the synthesis of total sterols appears to be limited normally by HMGR activity, these results indicate that the activity of one or more later enzyme(s) in the pathway must also be involved in determining the relative accumulation of end-product sterols. The levels of other isoprenoids such as carotenoids, phytol chain of chlorophyll, and sesquiterpene phytoalexins were relatively unaltered in the transgenic plants. It appears from these results that compartmentation, channeling, or other rate-determining enzymes operate to control the accumulation of these other isoprenoid end products.