+ar ADDITIONAL INFORMATION. IF ANY. CONCERNING AUTHORS, ADDRESS, TITLE, OR CITATION DATA PLEASE TYPE ABSTRACT DOUBLE SPACED BELOW MUCHMORE, ANDREW V. (Hopkins Marine Station of Stanford University, Pacific Grove, California). Laminarinase and Hexokinase Activity during Embryonic Development of Acmaea scutum (Mollusca: Gastropoda: Prosobranchia). The Veliger Activity of embryonic carbohydrases, hexokinase, glucose-6-phosphate dehydrogenase, and isocitrate dehydrogenase were analyzed fluorometrically in the unfertilized eggs, trochophores, and veligers of the limpet Acmaea scutum. and socae were Glucose-6-phosphate,dehydrogenase activity, constant at all stages. Hexokinase activity increased almost three-fold between the trochophore and veliger stage. No maltase, galactosidase, or amylase activity was found at any stage. A laminarinase-type enzyme, capable of degrading algal laminarin to free glucose, was found in all embryonic stages. This enzyme may be involved in digestion of laminarin when the embryo becomes a feeding larvae, or may be involved in intracellular breakdown of 8,1-3 linked glycoproteins during embryogenesis.-Author. PLEASE DO NOT TYPE BELOW THIS LINE 1 LAMINARINASE AND HEXOKINASE ACTIVITY DURING EMBRYONIC DEVELOPMENT OF ACMAEA (MOLLUSCA, GASTROPODA)1;2 Andrew V. Muchmore Hopkins Marine Station of Stanford University Pacific Grove, California Andrew V. Muchmor This report describes some enzyme activities related to carbohydrate metabolism during embryonic development of the gastropod, Acmaea scutum (Escholtz, 1833). Data are presented on activities of enzymes releasing free glucose from various polysaccharides, on hexokinase (an enzyme com- mon to both the pentose shunt and glycolysis), glucose-é¬ phosphate dehydrogenase (an enzyne of the pentose shunt), and isocitrate dehydrogenase (an enzyme of the citric acid eyele). MATERTALS AND METION Obtaining and culturing gametes: Adult A. scutum were collected from an area on Cypress Point in Pebble Beach, California. The animals were removed from their shell, and the dorsal body wall ruptured near the posterior end of the animal, with care taken not to puncture the nearby digestive gland. Parts of the ovaries from five females were removed with a forceps, agitated in alkaline sea water to remove the mature eggs, and then treated as described below to remove the chorion. Sperm were obtained by agitating the testes in 25 ml of normal filtered sea water, and filtering the suspension through a double layer of cheesecloth. Andrew V. Muchmore Removal of the chorion by the alkaline sea water treatment of Wolfson (1907) was necessary to obtain ferti- lization and normal development. For A. scutum, best results were obtained by 90 minutes incubation in alkaline sea water (2.5 ml of O.IN NaOH in 100 ml of filtered sea water, final phi 9.2). The alkaline sea water was then removed, the eggs resuspended in filtered sea water, and 1 ml of sperm suspension added. After two hours the eggs were agitated, allowed to settle, and the supernatant water containing most of the sperm removed and filtered sea water added. After about 36 hours, the embryos were gently centrifuged, and resuspended in freshly filtered sea water. Above operations were all performed at 15-17 C Enzyme preparation: Assays of one large group of eggs were made before fertilization, 24 hours after fertilization at the troco- phore stage, and 48 hours after fertilization at the veliger stage. In initial experiments, enzyme instabilit was noted, which suggested the possibility of degradative enzymes (such as proteases). Therefore, in some experi- ments 6-9 milligrams ovomucoid prepared by the method of Fredricq and Deutsch (1949) were added to one half of the samples as a specific trypsin inhibitor. Andrew V. Muchmore The eggs, trocophores, or veligers were divided into two parts and centrifuged. One sample was suspended in 2.5 ml buffer (0.05M TEA, pH7.6), the other in 2 mi buffer- 0.5 ml of ovomucoid solution (also suspended in buffer), and both samples then disrupted in a Dounce honogenizer at 0 degrees centigrade. The volumes of embryos used ranged from 0.05 - 0.1 ml packed cells per 2.5 ml. All preparations were assayed for enzyme activity at 26 degrees centigrade. Fluorometric assays: Because of the small amounts of embryos obtainable, sensitive fluorometric techniques, based upon the absorption of TrNI at 366 mu and its fluorescence at wavelengths greater than 420 mu were utilized to measure enzyme activity. Using incubation mixtures described below, glucose-6-phosphate dehydrogenase (C6PDh) and isocitrate dehydrogenase activity were determined by direct measurement of TPNH formation; hexokinase (HK) activity was measured by coupling its prod¬ uct, glucose-6-r04, with excess G6PDh, to yield TPNI; and carbohydrases releasing free glucose measured by coupling glucose production to HK and CoPDh in the presence of excess ATP. 1) Glucose-6-phosphate dehydrogenase: The 2 mi reaction mix contained, per ml, 43 umoles TEA buffer (pl 7.6) Andrew V. Muchnore 0.25 umoles TPN, 5 jmoles Ngcla, and 4 jumoles glucose-6- phosphate (G-6-P). (2) Hexokinase: Same as (1), except 10 jmoles/mi glucose were substituted for G-6-P, plus 2 umoles/ mi ATP, and O.5 ugms/ml CöPDh. 3) Carbohydrase: Same as (2), plus 2.5 ugms/ ml IK, and in place of glucose were substituted either maltose (1 pmole/ml), lactose (1 umole/ml), laminarin or starch (0.05%, final concentration). Negligible glucose was present in the starch, laminarin, or cell extract. Ap- preciable amounts, however, were found in the maltose and lactose. To eliminate this contribution, the reaction mix (minus cell extract) was incubated with sufficient substrate to remove all free glucose, and the reaction then initiated with cell extract. (4) Isocitrate dehydrogenase: Same as (1), except 2 umoles/ml isocitric acid was substituted for the G-6-P. Other assays! Unfertilized and veliger stages were also assayed for carbohydrases by measuring reducing sugars released, using the method of Somogyi as modified by Nelson (1944 As a further check, amylase activity was also measured qualitatively by adding iodine to samples of extract and starch at five-minute intervals, and using decolorization Andrew V. Muchmore of the blue iodine-starch complex as an indicator of amylase activity. The fluorometric technique was capable of detecting the production of as little as 6 x 10-11 moles glucose/min. The reducing sugar test of Somogyi as modified by Nelson could detect about 3 x 10-8 moles of reducing sugar. Protein was measured spectrophotometrically by both the method of Warburg and Christian (1941) and Lowry et. al. (1951). Protein content was assumed to reflect enzyme content, since the observed rates were closely related to enzyme concentration (a twofold increase in extract approx¬ imating a twofold increase in rate). The activities are therefore expressed as moles TPNI formed per minute per milligram protein. Commercial sources of enzymes and substrates: Hexokinase and glucose-6-phosphate dehydrogenase (Boehringer and Sohne), isocitrate, glucose, TFN, and ATP (Sigma Chemical Company), lactose (Nutritional Biochemical Corporation), and maltose (Difco Laboratories). The laminarin and starch were prepared by Dr. John Phillips of Hopkins Marine Station. RESULTS AND DISCUSSION: Enzyme activities determined fluorometrically, are isted in Table 1. The lack of amylase activity in unferti- lized eggs and in veligers was also supported qualitatively Andrew V. Muchmore by the lack of decolorization of the iodine-starch complex, and quantitatively by the reducing sugar test. This latter test indicated that, if amylase were present, it produces less than 30 x 10-9 moles reducing sugar per hour per mom protein. Enzyme extracts assayed for carbohydrase activit, were prepared from embryos obtained from different females. For comparison of enzyme activity during development, eggs of five females were pooled, and enzyme activity was deter. mined in the unfertilized egg, trocophore, and veliger stages. The rates of enzyme activity of these various stages are shown in Table I and Fig. I. Table I shows that by the veliger stage, regardless of previous activity, the embryos homogenized in ovomucoid show a greater activity than the extracts prepared without this trypsin-inhibiting compound. This could indicate the development of a trypsin¬ like protease. This conclusion is also supported by Fig. II, which shows that storage of IK at 0°c, without ovomucoid, results in considerable loss of activity, and that this loss does not occur with ovomucoid present. Similar stabilization of activity was also observed with laminarinase activity. Isocitrate dehydrogenase activity in the unfertilized eggs (Table I) shows anomalous behavior in ovomucoid which is unlike the activity of HK and zr. The reasons for this are unclear. 360 Andrew V. Muchmore Perhaps the most interesting discovery is that the eggs and early embryonic stages of A. scutum possess an enzyme (s) capable of releasing glucose from laminarin. The acwt rate of this enzyme, however, was non-linear under the pres- ent assay conditions, and therefore no comparison of activity was attempted. The role of the enbryonic laminarinase in the egg and early trocophore stages is difficult to visualize, since neither of these are feeding stages. The veliger, however, does feed, and could certainly utilize a minarinase-type enzyme for digestion of the large amount of algal laminarin found near the surf zone in small fragments of brown algae. If the veligers are degrading laminarin to free glucose in their natural environment the sharp increase in HK activity (Fig. 1), also found at this stage, could result from free glucose made available by laminarinase. ZF activity, however, appears to remain relatively constant during development. Another possibility, which is presently being investi gated, is that the observed laminarinase activity actually reflects 81,3 glucanase activity involved in the breakdown of cellular glyco-proteins. Andrew V. Muchmore SUNMMARY: Activity of embryonic carbohydrases, hexokinase, glucose-6-phosphate dehydrogenase, and isocitrate dehydro¬ genase were analyzed fluorometrically in the unfertilized eggs, trocophores, and veligers of the limpet Acmaea scutum. Glucose-6-phosphate dehydrogenase and isocitrate dehydro- genase activity was constant at all stages. Hexokinase activity increased almost threefold between the trocophore and veliger stage. No maltase, galactosidase, or amylase activity was detectable at any stage. A laminarinase-type enzyme, capable of degrading algal laminarin to free glucose was found in all embryonic stages. The role of laminarinase in unfertilized eggs is puzzling since the substrate for this enzyme is not available until feeding begins at the veliger stage. Andrew V. Muchmor ACKNOULEDGEMENTS The author is deeply indebted for help received from Dr. David Epel and Miss Sharon Proctor, both of Hopkins Marine Station. This work was made possible by Grant G1806 from the Undergraduate Research Participation Program of the National Science Foundation. Andrew V. Muchmore FOOTNOTES Page 1, 1) Permanent address: 2) The following abbreviations will be used: HK - hexokinase, G6PDh - glucose-6-phosphate dehydrogenase TEA - tri-ethanol amine buffer, TPN - triphospho pyridine nucleotide (NADP), and G-6-P - glucose-6-phosphate. - 12 - Andrew V. Muchmore LITER TURE CITED Fredricg, E. and H. F. Deutsch. 1949. Studies on Ovomucoid, Journ. Biol. Chem. 181:499-510. Lowry, Oliver H., N.J. Rosebrough, A.L. Farr, and R.J. Randall. 1951. Protein Measurement with the Folin Phenol Reagent. Journ. Biological Chemistry 193:265-275. Nelson, Norton 1944. A photometric Adaptation of the Somogyi method for the determination of glucose. Journal Biological Chemistry 153: 375-380. Warburg, O. and W. Christian. 1941. Protein F timation by Biochem. sch. O:384. Ultraviolet Absorption, B., Wolfsohn, Julian Mast. 1907. The Causation of Maturation in the Eggs of Limpets by Chemical Means, Biol. Bull., 3:345-350. 364 Andrew V. Muchmore FIGURE LEGENDS: Figure 1 - Activity of hexokinase during development. Activity expressed as 10-11 moles TPNH/minute/milligram protein. Figure 2 - Inactivation of trocophore-stage hexokinase during storage at 0°C. Activity expressed as 10-11 moles TPIN/minute/milligram protein. The top line is with ovomucoid, the bottom without ovomucoid. 36 1 TAOCHOPORE VEUIGER EGtr S7A6E (171) TIME (HeS.) 366 ndvend fjuehnde 713 2 Table I Enzyme Activities at Various Embryonic Stages trocophore same same egg Stage extract after extract after extract extract 24 hours time -O time - 0 24 hours Enzyme Hexokinase 3.8 3.8 3.7 3.5 with mucoid 0.8 3.5 2.2 with out mucoid Laminarinase 5 to 30 104 with mucoid with out mucoid Maltase with mucoid ith out mucoid Galactosidase with mucoid with out mucoid Amylase with mucoid with out mucoid Isocitrate dehydrogenase 35 43 with mucoid with out mucoid G-6-P dehydrogenase with mucoid 36 with out mucoid moles TPNH/minute/milligram protein Enzyme rates expressed as 10 The table also shows enzyme activity after "aging" of extract at O degrees centigrade for 24 hours in the presence and absence of ovomucoid. veliger extract 3.7 56 28 J