Odorivector

Most, perhaps all of the odor theories advanced so far made the assumption that the transcription of structureil information encoded in the stimulant molecule into an odor information pattern is an integral process One odorivector (AMOORE, 2) interacts with one receptor site and this interaction resvilts in transcription of all structural components simviltaneously into their corresponding informational modalities. However, observation tells us that olfactory information is inherently complex Ambergris for instance is described (OHLOFF, 3) by six distinctly different notes. This would imply that in an integral process of the periphersil molecular interaction one single neuron has to detect at least six different profiles with six different receptor sites and project the informational modalities intact to the higher centers. 

Adenyl cyclases are highly complex enzyme systems consisting of several interacting submits. The system described above contains a submit with two regulatory sites One for the odorivector which acts as an activator for the catalytic site of the adenyl cyclase system imbedded in a second submit. The other regulatory site in the first submit then can act as an allosteric regulatory site for activators or inhibitors and in this manner regulate the conformation of the specific odorivector receptor site. 

In short, ligand formation of one odorivector molecule with a receptor site having a complementary structure to structural elements of the odorivector would result in formation of a single bit of chemoreceptory information. The acceptor system is a modular system in which the transducer and the transponder can remain un-... 

It furthermore follows that a profile may constitute only a significant part of the overall structure of the odorivector molecule either a shape - the Van der Waals molecular outline proposed by AMOORE - which can degenerate to a molecularly defined plane or it can be a functional group in the traditional sense... 

In any case, whatever amount of structural modality may be contained in the odorivector structure has to be transcribed totally or partially in the transduction process. More precisely, this transcription process has to be effected in the peripheral interaction of the odorivector with the receptor site leading to ligand formation. The resilLting complex is bound by weak and reversible bonds, such as hydrogen bonds or Van der Waals forces. In most cases the receptor site is the proton donor, most likely through free thiol groups. In some special cases the reverse process, in which the odorivector acts as a proton donor, may be operational. 

In order to achieve weak bond formation the ligand has to fit into the receptor site in such a way as to bring weeik bond forming sites of the odorivector and the receptor site within striking distance. This is the same process as the one assumed in drug/ receptor interactions. It was recognized in molecular pharmacolo-... 

Odorivector molecviles can contain an almost unlimited number of profiles. Of these are only a few explicit, but with increasing conformational freedom a rapidly increasing number of implicit ones are potentially possible. This raises the question about the number of complementary receptor sites necessary to deal unambiguously and efficiently with the transcription of structural into informational modalities. The concept of multiple profile - multiple receptor sites provides no indication how the actual number of receptor site types covild be deduced. However the minimum number required to encode the total olfactory spectrum perceived by man can be estimated by means of basic principles of information theory. For that a few simple assmptions have to be made ... 

Therefore in any attempt of odor-structure correlation not the total (or overall) structure of the molecule should be considered but the individual contributions of the molecular profiles. Perhaps this could be done by a combination of computer assisted conformational analysis of the odorivectors which would provide information about the nature of the explicit and implicit profiles as well as the probability of the formation of the latter, with multidimensional scaling of the highly processed information the odorivectors deliver. 

Furthermore the odorivectors could be treated the same way, with the same methods, as drug molecules are in QSAR (Quantitative Structure Activity Correlation). A computerized approach to biochemical quantitative structure-activity-correlations was introduced by the HANSCH APPROACH (ll). Definition of all the essential profiles, those capable of being expressed in monoosmatic components, would afford the foundation on which an algorithm for the calculation of odor quality based on the chemical structure of the odorivector conceivably could be designed. 

Activation could raise the contribution of a minor mo-noosmatic component to either modifying or dominant status and thus create a noticeable synergistic effect. Both antagonistic and synergistic effects are very common in miilticomponent odorivector systems and are well known to experienced perfumers. 

U) These observed synergistic and antagonistic effects indicate that the regulatory activity has to be encoded in an odorivector present in the mixture, in all probability in the same way as the activators of the detector adei l cyclase - as an "Active Profile"... 

In all of these examples of regulation of transcription of profiles by allosteric regulation of receptor sites by active profiles THE DUAL NATURE OF ODORIVECTORS manifests itself. This is a new principle postulated to be pertinent in all mixtures of odorivectors. In its most extended scope this principle states that all odorivectors have two functions To display their own intrinsic odor and at the same time act as regulator in the odor perception of a copresent odorivector. The latter is achieved by allosteric regulation in a peripheral process. 

The Dual Nature of Odorivectors explains the observed nonlinear additivity of odors. In odor mixtures the contribution of each component is not necessarily the odor quality it would display if presented as a single odorant - the intrinsic odor - but an odor quality which is changed by the allosteric regulation caused by a co-present odorivector. The extent of this change is a function of the concentration of the regulatory odorivectors present. 

The concept of the Dual Nature of Odorivectors furthermore explains all observed irregularities, synergistic and antagonistic effects at least in part by assuming the causative processes take place at the periphery and not exclusively at the CNS-level as has been generally assumed so far. 

That this peripheral interaction of odorivectors is a reality and not Just a postulate resulting from lengthy speculations has been confirmed by statistically significant experimental proof obtained in malodor/"antlmalodor"-interaction studies (l ), and on a more general base, in odor/odor-interactions. These resiolts give implicit proof that specific receptor sites for moleciLLar and active profiles exist. 

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