Mark Roberts Anaerobic metabolism in snails ABSTRACT The existence of an anaerobic metabolic pathway which accumulates alanine and succinate was tested for in two snails which inhabit the intertidal region of the central Californian coast. Anaerobic con¬ ditions were induced by maintaining experimental animals in nitrogen flushed vials for 64 hours after which the whole soft tissue was assayed for alanine, succinate, and lactate. These assays were com¬ pared against the same for a set of controls. Results did not de¬ monstrate an accumulation of more alanine, succinate, or lactate in the snails under anaerobic conditions than in the aerobic controls. - 1 - Mark Roberts Anaerobic metabolism in snails INTRODUCTION Nst of the animals which inhabit the midtide forest are adapted for metabolizing carbohydrates via the oxygen requiring respiratory pathway common to most members of the animal kingdom. Being ma- rine, they are primarily adapted for respiration in an aquatic me¬ dium, though many are quite capable of aerial respiration when the tide is out. (12,14). However the capacity for aerial respiration is functional on¬ ly so long as the gill surface of the animal remains relatively wet.(12,14). When evaporative water loss becomes severe,aerial respiration must be halted to prevent the possibility of death due to dessication. (12,14). Numerous well known strategies and combinations of strategies are employed by the intertidal invertebrates for coping with this problem. These include: the use of oxygen stored in body fluids via respiratory pignents such as in the worm Urechis.(12), the use of oxygen trapped in mantle cavities as for example in certain. Littorine snails (12), and the use of some form of metabolic slow down akin to hibernation, such as the lowering of heart rate which occurs in the bivalve Mytilus Edulis (12). A final strategy, and the one of particular relevance to this 2 - Mark Roberts Anaerobic metabolism in snails paper is the transfer from aerobic to anaerobic metabolism which often occurs after the potential of the other methods has been exhausted(7,12,14,20). In most species, the switch to anaerobic metabolism is a switch to the lactate producing pathway of glycolysis (8). But not all invertebrates accumulate lactate during glycolysis (11,21). A¬ nother glycolytic pathway that employs the linkage of amino acid with carbohydrate metabolism has been shown to exist in a number of invertebrates (1,7,8,18) including the parasitic round worm Ascaris (15), and the intertidal bivalves Rangia, Crassostrea, and Volsella (2,6,18,19). The pathway is shown in figure 1. Some features to note in it are: 1). 8 moles of AIP are produced as oppossed to the 2 moles made during lactate-producing glycolysis and so it conveys an adaptive advantage to any organism capable of using it. 2). it accumulates succinate, alanine, and sometimes propionate instead of lactate. The existence of this pathway was investigated in two of the gastropods which inhabit the intertidal zone of central California 's rocky coast - Nucella Emarginata, and Acanthina Puntulata. These were selected for the following reasons: One of them, the Nucella belongs to a genus in which some other species have been shown to possess quantities of the enzymes malic dehydrogenase, lactate dehy¬ drogenase, pyruvate kinase, and pyruvate-carboxykinase in proportions - 3 - Mark Roberts Anaerobic metabolism in snails. that are characteristic of the animals which are known to have this pathway (2,16,17,18). In the lab, both species demonstrated an ability to survive for ar least 30 hours in a nitrogen flushed en¬ vironment - in the case of Nucella, the length of survival exc eded 5 days for 75% of the specimens. Both species are left dry for reasonably long periods during low tide, and are therefore suscep¬ table to the type of dessication stress that leads to anaerobiosis. Both have shells into which they may retreat during dry periods, thus closing off the organism from the oxygen containing medium which surrounds it. The build up of the end products alanine, and succinate can be used as a means to detect the existence of the pathway. The hypothesis upon which this paper is based is this - If this path¬ way is utilized in these snails, then those which have been placed under conditions which would induce anaerobiosis should possess a greater amount of these end products in their tissue then thos left to respire aerobicly. Furtheremore, there should be no sig¬ nificant difference in the lactate levels between the two. An assay for lactate was therefore also added. MATERTALS AND METHODS Two snails each were placed in 30 ml vials containing 0.5 ml of seawater, all flushed with 99.9% nitrogen gas for 60 seconds. The vials were capped, and taped closed, and the snails left to Mark Roberts Anaerobic metabolism in snails respire for 64 hours in a bath of 17° C water. An equal number of controls were placed in open vials and kept under the same condi¬ tions except that there was free exchange of oxygen between the vial and the air. After the test period, all animals were frozen in liquid nitrogen, and homogenized in perchloric acid according to the pro¬ cedure of Williamson (24) with only one modification; the whole snail was dropped into the liquid nitrogen instead of being frozen between freeze clamps. The extracts were then assayed for the end products according to Williamson (23) for alanine ; Williamson (24) for succinate with a modification in the concentration of AlP by a 10 fold increase; and according to Gutman (5) for lactate. All assays were spectrophotometric measurements of the change in absorbtion resulting from a change in the concentration of NADH according to the equations shown in figure 2. Figure 2 also gives a flow chart of the major steps in the experiment. RESULITS Based on an average consumption rate of 124 ul/g/hr of oxygen for a group of similar gastropods (4,12), and on an average animal weight of 2 grams per vial for the Nucella, and 5.3 grams'per vial for Acanthina, theloxygen in these vials should have been exhausted in less than 23 hours in the case of Nucella, and in less than 9 5 - Mark Roberts Anaerobic metabolism in snails for the Acanthina - even if the vials were not flushed with any nitrogen. Nitrogen flushing served to minimize both the possibilty of aquatic and aerial respiration, and also it minimized the possi¬ bility of death due to dessication because seawater could be left in the vial. A preliminary check on the sensitivity of the assays showed the alanine and lactate assays to be about 10 times less sensitive than expected. The succinate assay did not work at all, presum¬ ably because of instability in the enzyme succinic thiokinase which initiates the whole reaction. The succinate assay was therefore eliminated. The results (in change of absorbance) of the remaining two assays are shown in figure 3. CUSSIOV The high number of negative values for both the aerobic and anaerobic samples are difficult to explain. Both normal change in absorbance in blanks, and when NADH concentration is changed cause only positive changes in absorbance. Negative readings may have resulted from localized heating in the cuvettes, producing convec¬ tion currents which alter the absorbance of the solution. Another possibility is that there are some other compounds present in the mixture whose absorbance in UV light also decreases upon addition of the final reagent. The other explanation of negative results is that these numbers - 6. Mark Roberts Anaerobic metabolism in snails represent random changes in the overall absorbance of the solu¬ tion. If this were the case, all positive results within the same range of absolute values would also have to be considered random. Indeed, statistical tests indicated that the whole of the values obtained for both the aerobic, and anaerobic extracts were not significantly different than zero. This of course means that no difference between the experimental and control animals could be determined. Zero readings lend themselves to two interpretations. 1). there is no measurable increase in the alanine or lactate concen¬ trations when snails are kept under anaerobic conditions over when they are not, and so the animals do not possess the pathway in question, or they utilize a similar pathway which may accumulate succinate for exanple, but does not accumulate alanine or lactate. 2). The assay itself is not sensitive enough to measure the small concentrations of these products which for alanine should be near .78 mg/gram fresh tissue - assuming a value near the average for other gastropods (3). In light of the statistical finding that the numbers are not different than zero, the later explanation is most probable. In fact, when the concentrations inplied by these results were conpared to the minimum resolving ability of the assays according to the original authors it was found that the highest reading cor¬ responded to a concentration that was lower than the confident Anaerobic metabolism in snails Mark Roberts level of resolution by a factor of three. However if some justifiable reason for elimination of the negative readings could be found, some results fall out of this data. Certainly negative readings are impossible to interpret as they directly correspond to negative concentrations - which are impossible. If any of this data had a remote chance of being cor¬ rect, it would have to be the positive readings. Knowingly taking the experimental bias of considering all ne- gative values as zero readings, and all positive values as real, the results in figure 4 can be obtained. In the Nucella, the ave¬ rage accumulation of alanine was greater in the anaerobic animals than in the aerobic ones. The ratio of anaerobic to aerobic con¬ centration is an indication of how much greater. For Nucella this ratio is greater than 2.5. Also, the accumulation of lactate in the anaerobic tissue is only slightly greater than the same in the aerobic tissue. For the Acanthina, both the accumulation of ala¬ nine and lactate are nearly the same for both extracts. If these results were acceptable, they would indicate an af¬ firmitive conclusion regarding the existence of the pathway in fi¬ gure one in Nucella, and would imply that either the Acanthina does not have it, or that conditions were not sufficiently vigorous to force the snail into anaerobic metabolism. Anaerobic metabolism in snails Mark Roberts ONCLUSION Only by allowing for extreme experimental bias may it be said that any of this data provides evidence for or against the existence of succinate-producing glycolysis in these two snails. In light of the prior conclusion that the assays employed were not sensitve e- nough to detect any end products, the ultimate conclusion of this paper must be that the existence of this interesting biochemical pathway still awaits further investigation in these species. Mark Roberts Figure 1. Figure 2. Figure 3. Figure 4. Anaerobic metabolism in snails OS FIGURE CAPT Essentials of the succinate producing anaero¬ bic metabolism found in several invertebrates. Note the evolution of 8 moles of ATP and the accumulation of alanine, succinate, and propi¬ onate. Flow of steps in this experiment. Final assay for end productswere based on change in concen¬ tration of NAD according to these equations. Results of assays for alanine and lactate. The units are absorbtion, and represent the change in absorbtion which occurs in the assay mixture after addition of the enzymes. Change in absorbtion is directly related to concentration of end product. Relativeanounts of end products accumulated in anaerobic and aerobic tissue of Nucella and Acanthina. Results are based upon extreme expiremental bias as described in text. G3P 2 Moles ATP PEP ASPARTATE OXOX MLATE MATE PRVATE FUMRATE — 2 Moles ATP — E — FIGURE 1 GLUTAMTE KGA GLUTAMTE KGA — SUCCI-OA PETHAL-COA PROPIOENL-CA PRPIOWATI —) 2 Moles ATP 2 Moles ATP SAILS SMAILS ONTROL DPERIFENTAL e ES- EPEEE (Liquid Nitrogen) HODGEVIZE (Perchloric Acid) & EXTRACT CETTRIGUGE supernatant (Spectrophotometer) ASSAV ALANINE + NAD + H,O ADH PYRUVATE + NHA + NADH Increase in Abs. LACTATE + NAD + H,O — LDH PYRUVATE + Hr + NADH Increase in Abs. SUCCINATE + ATP + COA STK SUCCINYL-COA + P + ADP ADP + PEP PK ATP + PYRUVATE PYRUVATE + NADH + H LDH LACTATE + NAD Decrease in Abs. ALANINE Absorb. AR -.233 .103 .300 .470 .050 .060 .140 .070 -.920 -.890 -.069 —.043 -.088 -.044 .006 .097 -.047 265 .020 -.853 -.024 .171 020 070 ACANTHINA PUNCIULATA NUCELLA EMARGINATA JURI LACTATE Absorb. — AR -.056 -.066 430 .104 -.161 .042 .090 .320 -.028 -.055 -.388 -.394 .160 300 .085 .086 010 .064 2 Anaerobic Extract Rerobic Extract RATIO ANAEROBIC AEROBIC 2.66 1.7 .75 1.11 Nucella Emarginata ALANINE LACTATE Acanthina Puntulata FIGURE 4 Mark Roberts Anaerobic metabolism in snails BIBLIOGRAPHY & LITERATURE CITED 1. Awapara,J. and Simpson, J.W. - Comparative Physiology: Metabolism Ann. Rev. Physiol. 29: 87-112 1967. 2. Chen, Conrad and Awaparg,J. - Intracelluar Distribution of Enzymes Catalyzing Succinate Production from Glucose in Rangia. Comp. Biochem. Physiol 1965 Vol. 15: 1-6. 3. Flokin, Marcel - Nitrogen Metabolism. Chapter 10 in Physiology of 309-351. Academic Press 1966. Mollusca 4. Ghiretti, F. - Respiration. Chapter 5 in Physiology of Mollusca 175-208. Academic Press 1966. 5. 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