Magnetoreception

The vector of the geomagnetic field provides animals with directional information, while intensity and/or inclination provide them with positional information. For magnetoreception, two hypotheses are currently discussed: one proposing magnetite-based mechanisms, the other suggesting radical pair processes involving photopigments. Behavioral studies indicate that birds use both mechanisms: they responded to a short, strong magnetic pulse designed to change the magnetization of magnetite particles, while, at the same time, their orientation was found to be light-dependent and could be disrupted by high-frequency magnetic fields in the MHz range, which is diagnostic for radical pair processes. Details of these findings, together with electrophysiological and histological studies, suggest that, in birds, a radical pair mechanism located in the right eye provides directional information for a compass, while a magnetite-based mechanism located in the upper beak records magnetic intensity, thus providing positional information. The mechanisms of magnetoreception in other animals have not yet been analyzed in detail.     

Magnetoreception through Cryptochrome May Involve Superoxide

In the last decades, it has been demonstrated that many animal species orient in the Earth magnetic field. One of the best-studied examples is the use of the geomagnetic field by migratory birds for orientation and navigation. However, the biophysical mechanism underlying animal magnetoreception is still not understood. One theory for magnetoreception in birds invokes the so-called radical-pair model. This mechanism involves a pair of reactive radicals, whose chemical fate can be influenced by the orientation with respect to the magnetic field of the Earth through Zeeman and hyperfine interactions. The fact that the geomagnetic field is weak, i.e., ∼0.5 G, puts a severe constraint on the radical pair that can establish the magnetic compass sense. For a noticeable change of the reaction yield in a redirected geomagnetic field, the hyperfine interaction has to be as weak as the Earth field Zeeman interaction, i.e., unusually weak for an organic compound. Such weak hyperfine interaction can be achieved if one of the radicals is completely devoid of this interaction as realized in a radical pair containing an oxygen molecule as one of the radicals. Accordingly, we investigate here a possible radical pair-based reaction in the photoreceptor cryptochrome that reduces the protein's flavin group from its signaling state FADH^• to the inactive state FADH^- (which reacts to the likewise inactive FAD) by means of the superoxide radical, O₂^•-. We argue that the spin dynamics in the suggested reaction can act as a geomagnetic compass and that the very low physiological concentration (nM-μM) of otherwise toxic O₂^•- is sufficient, even favorable, for the biological function.     

隐花色素——生物磁感应蛋白

地磁场影响着自然界的生命活动,候鸟、果蝇等就利用地磁场进行导航迁徙．研究表明,鸟类的视网膜中存在一种蛋白名为隐花色素,作为最可能的磁感应分子和光受体. 该蛋白能够在光照条件下,产生自由基对,进行光化学转换．人体内也含有隐花色素蛋白,该蛋白也具有磁感应潜能．本文从地磁感应现象入手,结合最新的研究进展,重点介绍了隐花色素的结构、分类、光反应机制,并且根据光依赖的自由基假说就鸟类感应地磁场这一现象进行了简要阐述,同时对隐花色素研究前景进行了探讨．     

Two different types of light-dependent responses to magnetic fields in birds

A model of magnetoreception proposes that the avian magnetic compass is based on a radical pair mechanism, with photon absorption leading to the formation of radical pairs. Analyzing the predicted light dependency by testing migratory birds under monochromatic lights, we found that the responses of birds change with increasing intensity. The analysis of the orientation of European robins under 502 nm turquoise light revealed two types of responses depending on light intensity: under a quantal flux of 8.10(15) quanta m(-2) s(-1), the birds showed normal migratory orientation in spring as well as in autumn, relying on their inclination compass. Under brighter light of 54.10(15) quanta m(-2) s(-1), however, they showed a "fixed" tendency toward north that did not undergo the seasonal change and proved to be based on magnetic polarity, not involving the inclination compass. When birds were exposed to a weak oscillating field, which specifically interferes with radical pair processes, the inclination compass response was disrupted, whereas the response to magnetic polarity remained unaffected. These findings indicate that the normal inclination compass used for migratory orientation is based on a radical-pair mechanism, whereas the fixed direction represents a novel type of light-dependent orientation based on a mechanism of a different nature.     

Magnetic Compass of Birds Is Based on a Molecule with Optimal Directional Sensitivity

The avian magnetic compass has been well characterized in behavioral tests: it is an “inclination compass” based on the inclination of the field lines rather than on the polarity, and its operation requires short-wavelength light. The “radical pair” model suggests that these properties reflect the use of specialized photopigments in the primary process of magnetoreception; it has recently been supported by experimental evidence indicating a role of magnetically sensitive radical-pair processes in the avian magnetic compass. In a multidisciplinary approach subjecting migratory birds to oscillating fields and using their orientation responses as a criterion for unhindered magnetoreception, we identify key features of the underlying receptor molecules. Our observation of resonance effects at specific frequencies, combined with new theoretical considerations and calculations, indicate that birds use a radical pair with special properties that is optimally designed as a receptor in a biological compass. This radical pair design might be realized by cryptochrome photoreceptors if paired with molecular oxygen as a reaction partner.     

Angular Precision of Radical Pair Compass Magnetoreceptors

The light-dependent magnetic compass sense of night-migratory songbirds is thought to rely on magnetically sensitive chemical reactions of radical pairs in cryptochrome proteins located in the birds’ eyes. Recently, an information theory approach was developed that provides a strict lower bound on the precision with which a bird could estimate its head direction using only geomagnetic cues and a cryptochrome-based radical pair sensor. By means of this lower bound, we show here how the performance of the compass sense could be optimized by adjusting the orientation of cryptochrome molecules within photoreceptor cells, the distribution of cells around the retina, and the effects of the geomagnetic field on the photochemistry of the radical pair.     

Exploring the possibilities for radical pair effects in cryptochrome

The ability of some animals to sense magnetic fields has long captured the human imagination. In our recent paper, we explored how radical pair effects in the protein cryptochrome may underlie the magnetic orientation sense of migratory birds. Here we explain our model and discuss its relationship to experimental results on plant cryptochromes, as well as discuss the next steps in refining our model, and explore alternate but related possibilities for modeling and understanding cryptochrome as a magnetic sensor.Key words: cryptochrome, radical pair machanism, avian orientation, magnetic field effect, Arabidopsis thaliana, avian magnetoreception, magnetic sensorThe ability of some animals to sense magnetic fields is a long-standing open problem in biology. Over the past 50 years, scientific studies have shown that a wide variety of living organisms have the ability to perceive magnetic fields and can use information from the earth''s magnetic field in orientation behavior. The best-studied example of animal magnetoreception is the case of migratory birds, who use the earth''s magnetic field, as well as a variety of other environmental cues, to find their way during migration.The two prevailing hypotheses for the mechanism of avian magnetoreception are an iron-mineral-based explanation, wherein birds use small deposits of magnetic iron minerals^1,2,12 in the base of their beaks for magnetic orientation, and a radical-pair-based explanation, in which a magnetically sensitive chemical reaction in the eye of the bird enables perception of the magnetic field via its effects on reaction products. The latter hypothesis is based on the idea that a radical pair reaction may take place in the protein cryptochrome in the retina of the bird.^3,4 Cryptochrome contains a blue-light-absorbing chromophore, flavin adenine dinucleotide (FAD); this FAD cofactor is reduced via a series of light-induced electron transfers from a chain of three tryptophans that bridge the space between FAD and the protein surface (see Fig. 1). The hypothesis explored in our paper⁴ is that a radical pair reaction takes place between FAD and the tryptophans in the photoreduction pathway which modulates the signaling activity of cryptochrome. The specifics of this idea are outlined in Figure 1.Open in a separate windowFigure 1Right: Cryptochrome internally binds the FAD cofactor and contains a three-tryptophan photoreduction pathway conserved from photolyase, consisting of Trp400, Trp377, and Trp324, with Trp400 nearest the FAD and Trp324 closest to the protein surface. After the FAD cofactor absorbs a photon, bringing it into an excited state, it is protonated from a nearby acidic residue, and then electron transfer proceeds from Trp400. At this stage, the semireduced FADH and Trp400⁺ comprise a radical pair—that is, each partner has an unpaired electron, and the spins of those electrons are in a correlated state. Cryptochrome is thought to be in its active, signaling state when the FAD cofactor is in this semireduced FADH form. An electron is then transferred from Trp377 to Trp400 and from Trp324 to Trp377, forming radical pairs FADH + Trp377⁺ and FADH + Trp324⁺ in the process. The Trp324 radical is then deprotonated. Before this final deprotonation, it is possible for the electron to back transfer from the tryptophan to FADH. If this occurs, FADH reverts to the oxidized FAD form, and cryptochrome is no longer in its active state. Left: This schematic of the electron transfer pathway in cryptochrome shows the estimated lifetimes of each of the radical pair states. The system spends most of its time in the FADH + Trp324 radical pair state. Also shown are the electron and nuclear spins on the FADH and Trp324 radicals. Each nuclear spin adds a small contribution to the local magnetic field. The unpaired electron spins are shown here in the singlet (antiparallel) state. They precess around the local magnetic field, which consists of contributions from the external field and from each of the nuclear spins, causing interconversion to the triplet (parallel) state and back again. This singlet-triplet interconversion is the basis of the radical pair effect in the following sense. Electron back-transfer from Trp324 to FADH proceeds only when the unpaired electrons on each radical are in the singlet state. Cryptochrome remains in its active state so long as this back-transfer is impeded. Therefore, singlet-triplet interconversion influences the time cryptochrome can spend in its active state, and so this magnetic-field-driven effect can alter the protein''s signaling behavior.That magnetic field effects do occur in cryptochrome is supported indirectly by experiments done by Margaret Ahmad and co-workers, as reported in their recent paper⁵ on the effects of magnetic fields on cryptochrome-dependent responses in Arabidopsis thaliana seedlings. In our paper, Magnetic Field Effects in Arabidopsis thaliana Cryptochrome-1 (4), we sought to evaluate this possibility computationally, to see whether a magnetic field effect in the FADH - tryptophan radical pair is reasonable. We found that it is possible to see a change in cryptochrome activation yield (the amount of time cryptochrome stays in its active state) of about 10%.Unfortunately, the magnetic field dependence of cryptochrome activation seen in our calculations cannot be taken as exact because of several limitations. Chief among these are that the models of the radical pair did not include all nuclei, and the hyperfine coupling constants were taken from DNA photolyase, which is a protein highly similar to cryptochrome in structure, but which does not necessarily have precisely the same hyperfine coupling for the FAD cofactor and the tryptophans in the photoreduction pathway as does cryptochrome. However, the suggested theory is general and with the knowledge of correct hyperfine coupling constants for the radical pair partners it can be used to calculate the activation yield precisely. Although it would be ideal to obtain hyperfine parameters from experiment, it is also possible to calculate the hyperfine coupling constants with advanced ab initio techniques using the Gaussian package.⁶ Our preliminary calculations of the hyperfine couplings in tryptophan radicals compare well with the values used in our paper.⁴ This sort of calculation creates the opportunity not only to refine our current picture of the radical pair mechanism in cryptochrome, but also to explore other possible radical pairs in the system.In light of work being done by Margaret Ahmad and co-workers (not yet published), it has been suggested recently that the radical pair reaction in cryptochrome may not occur between the FAD cofactor and tryptophan, but in some other radical pair within the protein. It is possible that rather than occurring in the FAD photoreduction process, the radical pair reaction actually takes place in the reoxidation reaction wherein the semireduced FADH is brought back to the oxidized FAD form. One possible radical pair in the back reaction is between FAD and an oxygen molecule which is thought to be involved in the reoxidization process. This radical pair is of particular interest because an oxygen radical would be devoid of hyperfine interactions. Such a radical pair, where one radical has no hyperfine coupling, would be consistent with studies on the effects of weak radio-frequency oscillating magnetic fields on migratory bird orientation. Thorsten Ritz and co-workers found that appropriate orientation behavior depended not only on the strength and angle of the oscillating field, but also that the minimum field strength necessary to disrupt orientation depended on the frequency of the oscillating field in a resonance-like behavior that would be predicted by just such a radical pair^7–9 (personal communication with T. Ritz).The scientific community is still a long way from a complete understanding of avian magnetoreception. The best that may be said of our understanding of it is that birds do demonstrably perceive and use magnetic field information, and that their responses to magnetic fields under different conditions—light intensity and color, magnetic field strength and presence and frequency of oscillating fields—belies a complex phenomenon which is probably the result of multiple receptors which interact in unknown ways.^10,11 However, disorientation responses to low-intensity oscillating magnetic fields are strongly suggestive of the involvement of a radical-pair mechanism, making the exploration of radical pair effects in cryptochrome a useful endeavor. Much remains to be done. Even if cryptochrome is confirmed as magnetoreceptor, it remains for biologists to determine how its signaling modulation enters into a bird''s sensory perception and ultimately its orientation behavior. Nevertheless, radical pair effects in cryptochrome seem promising as a possible source of magnetoreception in birds, and continued investigation may yet shed light on this complex behavior.     

The puzzle of magnetic resonance effect on the magnetic compass of migratory birds

Experiments on the effect of radio‐frequency (RF) magnetic fields on the magnetic compass orientation of migratory birds are analyzed using the theory of magnetic resonance. The results of these experiments were earlier interpreted within the radical‐pair model of magnetoreception. However, the consistent analysis shows that the amplitudes of the RF fields used are far too small to noticeably influence electron spins in organic radicals. Other possible agents that could mediate the birds' response to the RF fields are discussed, but apparently no known physical system can be responsible for this effect. Bioelectromagnetics 30:402–410, 2009. © 2009 Wiley‐Liss, Inc.     

Radical pairs may explain reactive oxygen species-mediated effects of hypomagnetic field on neurogenesis

Exposures to a hypomagnetic field can affect biological processes. Recently, it has been observed that hypomagnetic field exposure can adversely affect adult hippocampal neurogenesis and hippocampus-dependent cognition in mice. In the same study, the role of reactive oxygen species (ROS) in hypomagnetic field effects has been demonstrated. However, the mechanistic reasons behind this effect are not clear. This study proposes a radical pair mechanism based on a flavin-superoxide radical pair to explain the modulation of ROS production and the attenuation of adult hippocampal neurogenesis in a hypomagnetic field. The results of our calculations favor a singlet-born radical pair over a triplet-born radical pair. Our model predicts hypomagnetic field effects on the triplet/singlet yield of comparable strength as the effects observed in experimental studies on adult hippocampal neurogenesis. Our predictions are in qualitative agreement with experimental results on superoxide concentration and other observed ROS effects. We also predict the effects of applied magnetic fields and oxygen isotopic substitution on adult hippocampal neurogenesis.     

Role of exchange and dipolar interactions in the radical pair model of the avian magnetic compass

It is not yet understood how migratory birds sense the Earth's magnetic field as a source of compass information. One suggestion is that the magnetoreceptor involves a photochemical reaction whose product yields are sensitive to external magnetic fields. Specifically, a flavin-tryptophan radical pair is supposedly formed by photoinduced sequential electron transfer along a chain of three tryptophan residues in a cryptochrome flavoprotein immobilized in the retina. The electron Zeeman interaction with the Earth's magnetic field (∼50 μT), modulated by anisotropic magnetic interactions within the radicals, causes the product yields to depend on the orientation of the receptor. According to well-established theory, the radicals would need to be separated by >3.5 nm in order that interradical spin-spin interactions are weak enough to permit a ∼50 μT field to have a significant effect. Using quantum mechanical simulations, it is shown here that substantial changes in product yields can nevertheless be expected at the much smaller separation of 2.0 ± 0.2 nm where the effects of exchange and dipolar interactions partially cancel. The terminal flavin-tryptophan radical pair in cryptochrome has a separation of ∼1.9 nm and is thus ideally placed to act as a magnetoreceptor for the compass mechanism.     

Magnetic orientation and magnetoreception in birds and other animals

Animals use the geomagnetic field in many ways: the magnetic vector provides a compass; magnetic intensity and/or inclination play a role as a component of the navigational map, and magnetic conditions of certain regions act as sign posts or triggers, eliciting specific responses. A magnetic compass is widespread among animals, magnetic navigation is indicated e.g. in birds, marine turtles and spiny lobsters and the use of magnetic sign posts has been described for birds and marine turtles. For magnetoreception, two hypotheses are currently discussed, one proposing a chemical compass based on a radical pair mechanism, the other postulating processes involving magnetite particles. The available evidence suggests that birds use both mechanisms, with the radical pair mechanism in the right eye providing directional information and a magnetite-based mechanism in the upper beak providing information on position as component of the map. Behavioral data from other animals indicate a light-dependent compass probably based on a radical pair mechanism in amphibians and a possibly magnetite-based mechanism in mammals. Histological and electrophysiological data suggest a magnetite-based mechanism in the nasal cavities of salmonid fish. Little is known about the parts of the brain where the respective information is processed.     

Interaction of magnetite-based receptors in the beak with the visual system underlying 'fixed direction' responses in birds

Background

European robins, Erithacus rubecula, show two types of directional responses to the magnetic field: (1) compass orientation that is based on radical pair processes and lateralized in favor of the right eye and (2) so-called 'fixed direction' responses that originate in the magnetite-based receptors in the upper beak. Both responses are light-dependent. Lateralization of the 'fixed direction' responses would suggest an interaction between the two magnetoreception systems.

Results

Robins were tested with either the right or the left eye covered or with both eyes uncovered for their orientation under different light conditions. With 502 nm turquoise light, the birds showed normal compass orientation, whereas they displayed an easterly 'fixed direction' response under a combination of 502 nm turquoise with 590 nm yellow light. Monocularly right-eyed birds with their left eye covered were oriented just as they were binocularly as controls: under turquoise in their northerly migratory direction, under turquoise-and-yellow towards east. The response of monocularly left-eyed birds differed: under turquoise light, they were disoriented, reflecting a lateralization of the magnetic compass system in favor of the right eye, whereas they continued to head eastward under turquoise-and-yellow light.

Conclusion

'Fixed direction' responses are not lateralized. Hence the interactions between the magnetite-receptors in the beak and the visual system do not seem to involve the magnetoreception system based on radical pair processes, but rather other, non-lateralized components of the visual system.     

Acuity of a Cryptochrome and Vision-Based Magnetoreception System in Birds

The magnetic compass of birds is embedded in the visual system and it has been hypothesized that the primary sensory mechanism is based on a radical pair reaction. Previous models of magnetoreception have assumed that the radical pair-forming molecules are rigidly fixed in space, and this assumption has been a major objection to the suggested hypothesis. In this article, we investigate theoretically how much disorder is permitted for the radical pair-forming, protein-based magnetic compass in the eye to remain functional. Our study shows that only one rotational degree of freedom of the radical pair-forming protein needs to be partially constrained, while the other two rotational degrees of freedom do not impact the magnetoreceptive properties of the protein. The result implies that any membrane-associated protein is sufficiently restricted in its motion to function as a radical pair-based magnetoreceptor. We relate our theoretical findings to the cryptochromes, currently considered the likeliest candidate to furnish radical pair-based magnetoreception.     

Model for magnetic field effects on radical pair recombination in enzyme kinetics.

A prototypical model for describing magnetic field effects on the reaction kinetics of enzymes that exhibit radical pair recombination steps in their reaction cycle is presented. The model is an extended Michaelis-Menten reaction scheme including an intermediate enzyme-substrate complex where a spin-correlated radical pair state exists. The simple structure of the scheme makes it possible to calculate the enzyme reaction rate explicitly by combining chemical kinetics with magnetic field-dependent spin kinetics (radical pair mechanism). Recombination probability is determined by using the exponential model. Simulations show that the size of the magnetic field effect depends on relations between different rate constants, such as 1) the ratio between radical pair-lifetime and the magnetic field-sensitive intersystem crossing induced by the hyperfine interaction and the delta g mechanisms and 2) the chemical rate constants of the enzyme reaction cycle. An amplification factor that is derived from the specific relations between the rate constants is defined. It accounts for the fact that although the magnetic field-induced change in radical pair recombination probability is very small, the effect on the enzyme reaction rate is considerably larger, for example, by a factor of 1 to 100. Model simulations enable a qualitative comparison with recent experimental studies reporting magnetic field effects on coenzyme B12-dependent ethanolamine ammonia lyase in vitro activity that revealed a reduction in Vmax/KM at low flux densities and a return to the zero-field rate or an increase at high flux densities.     

Light-dependent orientation responses in animals can be explained by a model of compass cue integration

The magnetic compass sense of animals is currently thought to be based on light-dependent processes like the proposed radical pair mechanism. In accordance, many animals show orientation responses that depend on light. However, the orientation responses depend on the wavelength and irradiance of monochromatic light in rather complex ways that cannot be explained directly by the radical pair mechanism. Here, a radically different model is presented that can explain a vast majority of the complex observed light-dependent responses. The model put forward an integration process consisting of simple lateral inhibition between a normal functioning, light-independent magnetic compass (e.g. magnetite based) and a vision based skylight color gradient compass that misperceives compass cues in monochromatic light. Integration of the misperceived color compass cue and the normal magnetic compass not only explains most of the categorically different light-dependent orientation responses, but also shows a surprisingly good fit to how well the animals are oriented (r-values) under light of different wavelength and irradiance. The model parsimoniously suggests the existence of a single magnetic sense in birds (probably based on magnetic crystals).     

Avian magnetic compass: Its functional properties and physical basis

The avian magnetic compass was analyzed in bird species of three different orders - Passeriforms, Columbiforms and Galliforms - and in three different behavioral contexts, namely migratory orientation, homing and directional conditioning. The respective findings indicate similar functional properties: it is an inclination compass that works only within a functional window around the ambient magnetic field intensity, it tends to be lateralized in favor of the right eye, and it is wavelength-dependent, requiring light from the short-wavelength range of the spectrum. The underlying physical mechanisms have been identified as radical pair processes, spin-chemical reactions in specialized photopigments. The iron-based receptors in the upper beak do not seem to be involved. The existence of the same type of magnetic compass in only very distantly related bird species suggests that it may have been present already in the common ancestors of all modern birds, where it evolved as an all-purpose compass mechanism for orientation within the home range.     

Magnetic field protects plants against high light by slowing down production of singlet oxygen

Recombination of the primary radical pair of photosystem II (PSII) of photosynthesis may produce the triplet state of the primary donor of PSII. Triplet formation is potentially harmful because chlorophyll triplets can react with molecular oxygen to produce the reactive singlet oxygen (1O?). The yield of 1O? is expected to be directly proportional to the triplet yield and the triplet yield of charge recombination can be lowered with a magnetic field of 100-300 mT. In this study, we illuminated intact pumpkin leaves with strong light in the presence and absence of a magnetic field and found that the magnetic field protects against photoinhibition of PSII. The result suggests that radical pair recombination is responsible for significant part of 1O? production in the chloroplast. The magnetic field effect vanished if leaves were illuminated in the presence of lincomycin, an inhibitor of chloroplast protein synthesis, or if isolated thylakoid membranes were exposed to light. These data, in turn, indicate that 1O? produced by the recombination of the primary charge pair is not directly involved in photoinactivation of PSII but instead damages PSII by inhibiting the repair of photoinhibited PSII. We also found that an Arabidopsis thaliana mutant lacking α-tocopherol, a scavenger of 1O?, is more sensitive to photoinhibition than the wild-type in the absence but not in the presence of lincomycin, confirming that the target of 1O? is the repair mechanism.     

A model for photoreceptor-based magnetoreception in birds

A large variety of animals has the ability to sense the geomagnetic field and utilize it as a source of directional (compass) information. It is not known by which biophysical mechanism this magnetoreception is achieved. We investigate the possibility that magnetoreception involves radical-pair processes that are governed by anisotropic hyperfine coupling between (unpaired) electron and nuclear spins. We will show theoretically that fields of geomagnetic field strength and weaker can produce significantly different reaction yields for different alignments of the radical pairs with the magnetic field. As a model for a magnetic sensory organ we propose a system of radical pairs being 1) orientationally ordered in a molecular substrate and 2) exhibiting changes in the reaction yields that affect the visual transduction pathway. We evaluate three-dimensional visual modulation patterns that can arise from the influence of the geomagnetic field on radical-pair systems. The variations of these patterns with orientation and field strength can furnish the magnetic compass ability of birds with the same characteristics as observed in behavioral experiments. We propose that the recently discovered photoreceptor cryptochrome is part of the magnetoreception system and suggest further studies to prove or disprove this hypothesis.     

Magnetic field effects on coenzyme B12-dependent enzymes: Validation of ethanolamine ammonia lyase results and extension to human methylmalonyl CoA mutase

Enzymes with radical-pair intermediates have been considered as a likely target for purported magnetic field effects in humans. The bacterial enzyme ethanolamine ammonia lyase and the human enzyme methylmalonyl-CoA mutase catalyze coenzyme B₁₂-dependent rearrangement reactions. A common step in the mechanism of these two enzymes is postulated to be homolysis of the cobalt-carbon bond of the cofactor to generate a spin-correlated radical pair consisting of the 5′-deoxyadenosyl radical and cob(II)alamin [Ado^· Cbl(II)]. Thus, the reactions catalyzed by these enzymes are expected to be sensitive to an applied magnetic field according to the same principles that control radical pair chemical reactions. The magnetic field effect on ethanolamine ammonia lyase reported previously has been corroborated independently in one of the authors' laboratory. However, neither the human nor the bacterial mutase from Propionibacterium shermanii exhibits a magnetic field effect that could be greater than about 15%, considering the error limit imposed by the uncertainty of the coupled assay. Our studies suggest that putative magnetic field effects on physiological processes are not likely to be mediated by methylmalonyl-CoA mutase. Bioelectromagnetics 18:506–513, 1997. © 1997 Wiley-Liss, Inc.