LI, S.; WAGNER, C. A. ; FRIESEN, J. A. ; BORST, D. W. : HMG-CoA reductase and its regulation in the mandibular organ of the lobster, Homarus americanus

The mandibular organ (MO) of decapod crustaceans synthesizes methyl farnesoate (MF), a sesquiterpene that appears to be involved in several physiological functions. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) is known to be the rate-limiting step of terpene biosynthesis in other species. Therefore, we investigated the activity of this enzyme in the lobster MO using a novel partition assay. Enzyme activity was linear with protein concentration, but decreased slowly during an 80-min incubation. NADPH was a 1000-fold more effective as a cofactor than NADH. The observed Km of the lobster HMGR for HMG-CoA was 3.0 �M, approximately 10-fold lower than the Km of HMGR in mammals. HMGR activity in the lobster MO varied from 16 to 60 nmol/mg protein/min, levels that are about 100-fold higher than those observed in mammalian tissues. This high activity is consistent with the high levels of MF produced by this tissue. Eyestalk ablation, a procedure known to increase MF production in most crustaceans, caused an increase in HMGR activity of more than 2-fold. Treatment of eyestalk-ablated lobsters with an extract of the sinus gland (SG), a neurohemal organ previously shown to contain neuroendocrine peptides that decrease MF synthesis by the MO, lowered HMGR activity to levels observed in intact animals. These data provide the first analysis of a crustacean HMGR, an enzyme that appears to be an important component in the MF biosynthesis pathway. Furthermore, our data indicate that neuroendocrine compounds in the SG may regulate this enzyme. The lobster MO may be useful as a model system for investigating the regulation of HMGR. (Supported by NIH R15 HD37953-01 and NSF DBI 9978810 to DWB).