Molecular olfactory

Lancet D, Sadovsky E and Seidemann E 1993 Probability model for molecular recognition in biological receptor repertoires significance to the olfactory system Proc. Natl Acad. Sci. USA 90 3715-19... 

Olfactory receptors have been a subject of great interest (9). Much that has been postulated was done by analogy to the sense of sight in which there are a limited number of receptor types and, as a consequence, only three primary colors. Thus attempts have been made to recognize primary odors that can combine to produce all of the odors that can be perceived. Evidence for this includes rough correlations of odors with chemical stmctural types and the existence in some individuals having specific anosmias. Cross-adaptation studies, in which exposure to one odorant temporarily reduces the perception of a chemically related one, also fit into this hypothetical framework. Implicit in this theory is the idea that there is a small number of well-defined odor receptors, so that eventually the shape and charge distribution of a specific receptor can be learned and the kinds of molecular stmctures for a specified odor can be deduced. 

Olfactory and stereochemical similarities to benzaldehyde have been examined for a large number of homologs of benzaldehyde and nitrobenzene each with the Me, Et, i-Pr, or t-Bu group at the ortho, meta, or para position. There exists a strong correlation between the two the more closely a compound resembles benzaldehyde in molecular shape, the more similar it is to benzaldehyde in almond odour 46). 

The vertebrates produce, send and detect information which is conveyed by one or more molecular types. Chemical information of biological value (semiochemicals) which partly or wholly activates the accessory olfactory system (AOS) is transferred during intra- and inter-species communication. The compounds involved convey messages of social importance originating from the need to co-ordinate gamete release. It seems quite likely that gradual improvements by selection of semiochemical molecules and their receptors eventually enhanced the reproductive benefits both for the sender and for the receiver (Sorensen, 1996). The dual olfactory systems interpret chemical input to allow the discrimination of odour... 

Afshar M., Hubbard R. and Demaille J. (1998). Towards structural models of molecular recognition in olfactory receptors. Biochimie 80, 129-135. 

Allen W.K. and Akeson R. (1985). Identification of an olfactory receptor neuron subclass cellular and molecular analysis during development. Dev Biol 109, 393-401. 

Buck L. (1993). Receptor diversity and spatial patterning in the mammalian olfactory system. In The Molecular Basis of Smell and Taste Transduction (Chadwick D., et al., eds). John Wiley, London, Ciba Symposium 179, pp. 51-67. 

Farbman A.I., Buchholz J., Suzuki Y., Coines A. and Speert D. (1999). A molecular basis of cell death in olfactory epithelium. J Comp Neurol 414, 306-314. 

Yoshihara Y. and Mori K. (1997). Basic principles and molecular mechanisms of olfactory axon pathfinding. Cell Tissue Res 290, 457-463. 

The first G-protein a subunit to be identified was Gs. The a subunit of Gs (as) is responsible for stimulating adenylate cyclase (hence, the subscript s ) and is ADP-ribosylated and activated by CTx. Gs has at least four molecular variants. Some evidence exists that as can also enhance the activity of cardiac L-type Ca2+ channels, independently of their phosphorylation by cAMP-stimu-lated protein kinase A. Golf is a cyclase-stimulating homolog in the olfactory epithelium, activated by the large family of olfactory receptors. 

The mammalian olfactory system possesses enormous discriminatory power. It is claimed that humans can perceive many thousands of different odorous molecules, termed odorants. Even slight alterations in the structure of an odorant can lead to profound changes in perceived odor quality. One commonly cited example is carvone, whose L- and D-stereoisomers are perceived as spearmint and caraway, respectively. However, more subtle molecular alterations can also generate striking changes in perception. 

Mori, K. and Yoshihara, Y. Molecular recognition and olfactory processing in the mammalian olfactory system. Prog. Neurobiol. 45 585-619,1995. 

Even though well-characterized at a biophysical level, the mechanical transduction mechanism of hair cells is still not fully understood in molecular terms. This discrepancy is in part due to the extreme scarcity of hair cells instead of the millions or even hundreds of millions of receptor cells that the olfactory and visual systems possess, only a few tens of thousands of hair cells are found in the internal ears of most vertebrate species. The small number of hair cells and the direct transduction mechanism has greatly impeded molecular biological and... 

FROM STIMULANT MOLECULE TO MOLECULAR IMAGES IN THE OLFACTORY SYSTEM... 

Different odor substances stimulate different patterns of ORCs in the olfactory epithelium, owing to the different sensitivity spectra of the ORCs (28). The pattern of activity in the epithelium evoked by a particular odor substance constitutes the first molecular image of that stimulus, which represents the determinants of the stimulating molecules (13). Thus, although olfaction is not a spatial sensory modality, in contrast, for example, to vision and somatosensation, the initial representation of an odor stimulus in the olfactory pathway does have spatial structure. 

An important insight from many studies (28) is that the response patterns—the molecular images—at various levels in the central olfactory pathway are set up by the differential responses of the ORCs in the peripheral receptor epithelium. These studies also suggest that functional modules, which may correspond to recognizable structural units such as individual glomeruli with their associated cells, in the olfactory bulb or lobe participate in the analysis of olfactory information conveyed to them... 

The number of carbon atoms of saturated straight-chain compounds correlates with hydrophobicity, molecular volume, and molecular length. All three could affect the interaction of an odorant ligand with the olfactory receptors (Johnson and Leon, 2001). 

The receptors start a second messenger cascade that is initiated by activation of G-proteins in the cell. These, in turn, interact with membrane-bound adenylyl cyclase, which catalyzes the formation of cyclic adenine monophosphate (cAMP) and opening of cAMP-gated cation channels. Depolarization then brings about an action potential, which travels along the axon of the olfactory sensory neuron. Many of the molecular components of this cascade are olfactoiy specific. 

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