X-Message-Number: 4752 Date: Thu, 10 Aug 1995 18:33:54 +0200 (MET DST) From: Eugen Leitl <> Subject: nature's cryonics (IV) P.W. Hochachka/G.N. Somero, "Biochemical Adaptation", Chapter 7: Off-Switches in Metabolism: From Anhydrobiosis to Hibernation. Some selected fragments containing close links to cryonics. This is the last post containing "Biochemical Adaptation" material. -- Eugene =-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-= When and Why Animals Turn Down Metabolic Rate There are numerous examples in nature of animals entering dor- mant or semidormant states for variable time periods. For example, for surviving the total dehydration that may occur when Artemia encoun- ter completely desiccated conditions, this small crustacean enters a period of encystment and metabolic arrest, which can last indefinitely. Such anhydrobiosis, although dramatic, is not unique to this particular organism. Another complex, multicellular animal that can totally de- hydrate without ill effects is the larva of a chyromid fly (Polypedilum vanderplanki). This larva lives in shallow and exposed rock pools in Nigeria and Uganda. At the beginning of the rainy seasons the pools may fill and dry several times, and they may occasionally be filled with water for short periods during the dry season. When the pools dry up the larvae also dry up and remain dry until the next rains. The degree to which the larvae dry up depends upon humidity. At a relative humidity of 60 percent their moisture content is 8 percent and it falls below 3 percent at <1 percent relative humidity. The larvae can rehydrate in water within about an hour, at which time their nor- mal moisture content from 80 to 90 percent is restored and they may actually be feeding again (Hinton, 1968). The larvae are thus adapted to an environment which is subject to flooding alternating with periods of extreme drought. A similiar capacity is known for rotifers, tardigrades, and nematodes, and is probably relatively widespread among lower invertebrates. The function of such anhydrobiological states is to survive in places that periodically suffer a complete lack of water; during such times, there is no possibility to obtain food in the usual sense of that term and it is therefore advantageous to turn down metabolism maximally. In these "dry biological systems" metabolic rates can fall to zero, thus completely removing a requirement for nutrition. [...] Anhydrobiosis and Anhydrobiotic Organisms So well established is the biological principle that water is essential for life that it may come as a surprise to some readers to learn of numerous exceptions to this principle; all of these, however, involve inactive metabolic states. The ability to survive the loss of all cellular water (save perhaps that bound very tightly to macromolecules) with- out irreversible damage is actually quite widespread, being expressed in nearly all major taxa. Keilin (1959) introduced the term crypto- biosis ("hidden life"), but later workers prefer the term anhydrobiosis ("life without water") to describe the phenomenon. Two readily distinguishable groups of organisms exhibit anhydro- biosis: 1) organisms capable of anhydrobiosis only in their early devel- opmental stages - these include the seeds of plants, bacterial and fungal spores, the eggs and early embryos of certain crustaceans, and the larvae of certain insects; 2) organisms capable of anhydrobiosis during any stage of their life histories - these include certain protozoans, roti- fers, nematodes and tardigrades (Crowe, 1971). Despite this funda- mental difference between the two groups, from currently available information it appears that they share many similiar biochemical mech- ansisms allowing entrance into, and emergence from, the anhydrobio- tic state. We shall examine in some detail two well-studied systems, the brine shrimp (Artemia), which falls into the first category, and nematodes, which fall into the second category. General Morphological Features of Artemia Cysts [...] Water Content and Metabolic Rates of Artemia Cysts [...] The Roles of Glycerol and Trehalose In Artemia cysts, glycerol accounts for approximately 4 percent of dry weight, and trehalose constitutes up to 14 percent of dry weight. There exists a strong corellation between the accumulation of these two polyols and survival in the desiccated state. And, as discussed in the chapters on solute adaptations and temperature adaptations, poly- ols also appear to be important in osmoregulatory and freezing- resistant strategies. What properties do polyols posess that make them useful in situatations of water stress? Polyols may have two distinct functions in anhydrobiotic systems. On the one hand, polyols may serve as water substitutes, forming hy- drogen-bonded interactions with polar or charged entities of the cell, and thereby replacing water. In addition, polyols may have the impor- tant effect of stabilizing protein structure at low water activities. How this effect is achieved has been shown recently by Gekko and Timasheff (1981a,b). They showed that glycerol is effectively excluded from the highly structured water surrounding proteins. The addition of increas- ing amounts of glycerol to an aqueous solution containing proteins thus leads to an increase in protein structural stability. The thermo- dynamic arguments here are straightforward. If a protein unfolds (= denatures), a larger area of protein surface come into contact with the solvent phase, leading to increased amounts of highly structured water. Since glycerol is excluded from this structured water, the addition of glycerol favors the compact, folded (=native) structures of proteins. Thus, if the loss of cellular water during entry into the desiccated state leads to a destabilization of protein structure due, perhaps, to increased concentrations of low molecular weight species in the pro- teins's microenvironment, the addition of high concentrations of gly- cerol can be viewed as a strategy for keeping the proteins in native form during periods of desiccation. When desiccation is over and the need for a rapid reactivation of metabolism occurs, the battery of enzymes needed (for conventional metabolism, in Clegg's terminology) will be present in a functional state. Anhydrobiosis in Soil Nematodes [...] Morphological and Ultrastructural Changes during Dehydration in Nematodes [...] Metabolic Changes during Entrance into Anhydrobiosis in Nematodes Nematodes about to enter into anhydrobiosis share with Artemia cysts the important characteristic of being essentially closed systems: no nutrients as such enter the system and all metabolic adjustments that accompany dehydration must therefore be generated endoge- nously. Experimentally, this simplifies the problem of identifying the main metabolic adjustment occurring during dehydration; namely, _a redistribution of carbon arising from storage depots of glycogen and lipid into large intracellular pools of glycerol and trehalose_. The latter two metabolites increase dramatically in concentration during desic- cation, reaching levels of about 6 precent and 10 percent of dry weight, respectively, by the time the entrance into anhydrobiosis is completed (seventy-two hours). The rise in glycrol and trehalose is almost quanti- tatively accounted by depletion of glycogen and lipid, as may well be anticipated. Corellation between Polyhydroxy Alcohols and Survival Interestingly, there is a striking coincidence between the onset of synthesis of glycerol and trehalose and increased ability to survive ex- posure to dry air. When the glycerol or trehalose contents are plotted against percent survival, a linear relationship is obtained in both cases, with regression coefficients of 0.98 and 0.93 respectively. As in Artemia cysts this strongly suggests that survival in the desiccated state is de- pendant upon glycerol and trehalose contents. In view of the stabilizing effects of polyhydroxy alcohols on the structural integrity of enzymes and nucleic acids, this result is not entirely surprising and is in full agreement with the data on Artemia cysts. In addition, Crowe and his colleagues have proposed that these metabolites (glycerol in particular) may play an important role in meembrane stabilization during anhy- drobiosis. Similiar changes in polyhydroxy alcohols are known for other anhydrobiotic organisms as well. Metabolism at a Standstill during Anhydrobiosis Although data on metabolic events at different states of hydration, comparable ot those for Artemia cysts, are not available for nematodes, it is reported that desiccated nematodes do not consume O_2. Three decades ago, Becquerel was able to revive certain nematodes, rotifers, and tardigrades after they had been exposed to temperatures as low as 0.05 K. He estimated that at this low temperature metabolic processes, if they occur at all in the anhydrobiotic state, must proceed at only about 10^{-7} the rate of normally metabolizing specimens. Hinton (1968) argues that this is not metabolism in the normal sense in which that term is used. Thus it can be assumed, at least tentatively, that in nematodes, as in Artemia cysts, metabolism is at a standstill during anhydrobiosis. Arousal from Anhydrobiosis by Nematodes [...] Biological Significance of Anhydrobiosis [...] Finally, although anhydrobiosis may be viewed as an adaptational solution primarily to drought conditions, another important corollary of this state is a _tremendously increased tolerance to numerous other harsh environmental factors_. Anhydrobiotic organisms aree famous for their tolerance to extremely low, or extremely high, temperatures and pressures; they are tolerant also to organic chemicals, toxins, and anoxia. Given these kinds of advantages one can understand why an- hydrobiosis developed in various phylogenetic lines, apparently arising independantly each time it appeared in nature. Insect Diapause [...] Metabolic Organization during Overwintering Dormancy [...] /* Eurosta, goldenrod gall fly larvae: primarily, glycerol and sorbitol levels are drastically elevated, glycerol reaching 235 umol/g, sorbitol 145 umol/g as plateau values. Peak values can reach 0.4 M (sic) in gall fly larvae. Also cryoprotectant protein presence is suspected. */ Glycogen as the Precursor of Polyhydric Alcohols [...] [... irrelevant stuff ...] =-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-= Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=4752