Retinal molecules

The multiple spawning method described in Section IV.C has been applied to a number of photochemical systems using analytic potential energy surfaces. As well as small scattering systems [36,218], the large retinal molecule has been treated [243,244]. It has also been applied as a direct dynamics method. 

In 1990 the resolution was extended to 3 A, which confirmed the presence of the seven a helices (c). This structure also showed how these helices were connected by loop regions and where the retinal molecule was bound to bacteriorhodopsin. (Courtesy of R. Henderson.)... 

This electron microscopy reconstruction has since been extended to high resolution (3 A) where the connections between the helices and the bound retinal molecule are visible together with the seven helices (Figure 12.3c). The helices are tilted by about 20° with respect to the plane of the membrane. This is the first example of a high-resolution three-dimensional protein structure determination using electron microscopy. The structure has subsequently been confirmed by x-ray crystallographic studies to 2 A resolution. 

Binding of these ligands does not occur in a concave groove located on the surface of the receptor protein as otherwise often imagined. As described in Section 2.2.1, the x-ray structure of rhodopsin showed that retinal is bound deep in the seven-helical structure with major interaction points in TM-III and TM-VI, as well as the covalent attachment point in TM-VII. In fact, rhodopsin interacts with basically all transmembrane segments. Importantly, side-chains from the transmembrane helices cover the retinal molecule on all sides, and its binding site is found deep in the middle of... 

Interestingly, carotenoids more abundant in the blood plasma than zeaxanthin, such as lycopene, P-carotene, and P-cryptoxanthin, do not accumulate in the retina. RPE cells express p,p-carotene 15,15 -monooxygenase (BCO), formerly known as P-carotene 15,l5 -dioxygcnase, an enzyme that catalyzes the oxidative cleavage of P-carotene into two molecules of all-trans-retinal (Aleman et al., 2001 Bhatti et al., 2003 Chichili et al., 2005 Leuenberger et al., 2001 Lindqvist and Andersson, 2002). Therefore it may be suggested that p -carotene transported into RPE-cells is efficiently cleaved into retinal molecules. BCO cleaves also P-cryptoxanthin (Lindqvist and Andersson, 2002), and its absence in the retina may also be explained by its efficient cleavage to retinoids. However, lycopene, often the most abundant carotenoid in human plasma, cannot serve as a substrate for BCO, and yet it is not detectable in the neural retina (Khachik et al., 2002). 

The light-absorbing part of a rod cell contains the pigment rhodopsin, which consists of the opsin attached to the 11-cis-retinal molecule (1) (Figure 12.3). Free 11-cis-retinal absorbs in the ultraviolet, but when attached to opsin the absorption is in the visible region. 

Experiments were performed at 5°C in order to arrest the cis-trans isomerization of the protonated Schiff base. Spectra with one equivalent of acid and different mixing times showed one NOE cross-peak between H15 of the retinal molecule and the proton on the counterion, as shown for a mixing time of 0.4 s in Figure 10. The strong chemical shift dependence of the H15 resonance on the concentration of the acid dictated the use of less than one equivalent of the protonating formic acid, and therefore an incomplete protonation (>80%) of the retinal, in order to avoid an overlap between the formate and the H15 peaks in the spectrum. This should not affect the observed result since an average chemical shift, between those of HI 5 of the retinal in its nonprotonated and protonated... 

There are several different rhodopsins in the cones. All of them contain retinal molecules as light-sensitive components, the absorption properties of which are modulated by the different proportions of opsin they... 

This enzyme [EC 1.13.11.21] catalyzes the reaction of j8-carotene with dioxygen to produce two retinal molecules. Both iron ions and bile salts are required cofactors. 

If we neglect the exciton-vibration interaction (i.e., the operator Hi), the wave functions of collective vibrations and of coherent excitonic states of the retinal molecule (they are specified by quasi-momentum Hq and are the proper functions of the Hamiltonian Hoq) form an orthonormal basis... 

Figure 3.9 shows the effects of double deuteration of the C7=C8 or C11=C12 double bond and that of the C14—C15 single bond on the triplet-state CTI starting from the set of four ds isomers. The results can be summarized as follows (1) The 7,8-deuteration (7,8-D2) reduces the quantum yield of isomerization from the 7-cis to the all-trans isomer that includes rotation around the particular double bond to which deuterium substitution was made, and also, the quantum yield of isomerization from the 9-cis to the all-trans isomer around the neighboring double bond on the right-hand side of the retinal molecule (see Scheme 3.1). (2) The 11,12-deu-teration (11,12-D2) reduces the quantum yields of isomerization from the 7-cis, 9-cis, and 11-cis isomers to the all-trans isomer that include rotation around the particular cis-double bond to which deuterium substitution was made, and also, that around the neighboring double bonds on the left-hand side of the molecule. (3) The 14,15-deuteration (14,15-D2) slightly reduces the quantum yield of isomerization from the 11-cis isomer. (4) Practically no deuteration effects on the quantum yields of isomerization are seen at all starting from the 13-cis isomer [13]. Table 3.1 lists the quantum yields of isomerization per triplet species generated for the undeuterated and variously deuterated retinal isomers.

M FIGURE 5-13 Structural model of bacteriorhodopsin, a multipass transmembrane protein that functions as a photoreceptor in certain bacteria. The seven hydrophobic a helices in bacteriorhodopsin traverse the lipid bilayer. A retinal molecule (red) covalently attached to one helix absorbs light. The large class of G protein-coupled receptors in eukaryotic cells also has seven membrane-spanning a helices their three-dimensional structure is similar to that of bacteriorhodopsin. [After H. Luecke et al., 1999, J. Mol. Biol. 291 899.]... 

Oxidation with peracids gives epoxides, which can be re-reduced with lithium aluminum hydride (Scheme 5.4.2). Another typical carotene reaction is rapid oxidative or reductive bleaching, which may also occur in the solid state. Cross-linked polymers of unknown structure are formed (see Fig. 5.5.3). With age, fluorescent pigments accumulate in the retinal pigment epithelium. The major chromophore of this particular pigment contains a pyri-dinium ring with two polyene side chains. It can be synthesized from two retinal molecules and ethanolamine via the enamine of retinal and condensation with a second retinal molecule (Scheme 5.4.3) (Eldred and Lasky,1993 Sakai et al.,1996). 

Fig. 15.1. A universal biological sensor based on ifaodopsin (a protein), a schematic view, (a) The sensor consists of seven a-helices (shown here as ribbons) connected in a sequential way by some oligopeptide links. The molecule is anchored in the cell wall (lipid bilayer), due to the hydrophobic effect the ihodopsin s lipophilic amino acid residues are distributed on the ihodopsin surface, (b) The a—helices (this time shown for simplicity as cylinders) form a cavity. Some of the cylinders have been cut out to display a cis-retinal molecule bound (in one of the versions of the sensor) to the amino acid 296 (lysine denoted as K, in heUx 7). (c) The ds-retinal (a drain of alternating single and double bonds) is able to absorb a photon and change its conformation to bans (at position 11). This triggers the cascade of processes responsible for our vision. The protrading protein loops exhibit specihe interactions with some drags. Such a system is at the basis of the interactions with about 70% of drags.

A variety of small molecules called transcription factors, or put simply copying factors, achieve finer control of genes. Vitamin A (which is found in carrots and has resemblance to the retinal molecule) is such a transcription factor. It causes the copying of genes that are responsible for growth and for maturation of cells, especially skin cells. 

The molecule of the derivative retinal (see figure below) is an alkene with conjugated double bonds. As we have already mentioned the conjugated molecules have the property to absorb visible light. Upon the absorption of a photon the retinal molecule is transformed from the Z- to the -isomer. This change in the molecular stereochemistry triggers the signal by which the information about the absorption of a photon is transferred to the nervous system. 

The length (width) of the potential well, L, equals the total length of the conjugated part of retinal molecule. 

This is the energy of the HOMO-LUMO gap in our model of the retinal molecule. Note that, like in thermodynamics, physical chemists often write E when in fact this is AE, a difference between two energies. And - you will calculate the HOMO-LUMO energy difference for any other molecule or atom in exactly the same way. Now what The second part of the question (B) is. What is the wavelength of the light that corresponds in energy to the HOMO-LUMO gap in retinal We will answer this, and all other questions of this kind, with the help of the following assumption. 

This is the answer to the problem the wavelength of the photon of light that can make a jr-electron in the retinal molecule jump across the HOMO-LUMO gap is 602 nm. This is within 5% of 578 nm, one of the wavelengths to which human eye is very sensitive. Our very simple model provided us an answer within the ballpark of a correct value. Now - this was quite a problem but you have also learned few things and you will be able to tackle any problem of this kind not a small achievement. 

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