Vision, retinol

A deficiency of vitamin A leads to vision defects, including a visual impairment at low light levels, termed night blindness. For the processes of vision, retinol needs to be converted first by oxidation into the aldehyde retinal, and then by enzymic isomerization to cw-retinal. c -Retinal is then bound to the protein opsin in the retina via an imine linkage (see Section 7.7.1) to give the red visual pigment rhodopsin. 

Vitamin A is the isoprenoid alcohol retinol, which is required for a number of body processes including vision, growth, maintenance of mucous membranes, reproduction and proper growth of the cartilage matrix upon which bone is deposited. Of these, the molecular basis of its role in the visual cycle is best understood. In addition to the alcohol retinol, both retinal and retinoic acid (Fig. 2.4) also act to restore some of the deficiency symptoms. In rod vision, retinol is oxidised to retinal. 11-ds-Retinal combines with the protein opsin to form rhodopsin. After the absorption of a photon, rhodopsin undergoes a series of changes, eventually dissociating to opsin and all-fraMS-retinal. This last compound is converted back to 11-ds-retinal by retinal isomerase (EC.5.2.1.3) Retinoic acid is able to replace retinol in all functions except the visual cycle and reproduction. 

Carotenoids absorb visible light (Section 13 21) and dissipate its energy as heat thereby protecting the organism from any potentially harmful effects associated with sunlight induced photochemistry They are also indirectly involved m the chemistry of vision owing to the fact that p carotene is the biosynthetic precursor of vitamin A also known as retinol a key substance m the visual process... 

Vitamin A (retinol) and its naturally occurring and synthetic derivatives, collectively referred to as retinoids (chemical structure), exert a wide variety of profound effects in apoptosis, embryogenesis, reproduction, vision, and regulation of inflammation, growth, and differentiation of normal and neoplastic cells in vertebrates. 

Vitamin A (retinol), present in carnivorous diets, and the provitamin (P-carotene), found in plants, form retinaldehyde, utilized in vision, and retinoic acid, which acts in the control of gene expression. Vitamin D is a steroid prohormone yielding the active hormone derivative calcitriol, which regulates calcium and phosphate metaboUsm. Vitamin D deficiency leads to rickets and osteomalacia. 

Vitamin A (retinol) and retinoic acid are carotenoid oxidation compounds that are very important for human health. The main functions of retinoids relate to vision and cellular differentiation. With the exception of retinoids, it was only about 10 years ago that other carotenoid oxidation products were first thought to possibly exert biological effects in humans and were implicated in the prevention - or promotion of degenerative diseases. A review on this subject was recently published. ... 

The central cleavage of P-carotene 1 is most likely the major pathway by which mammals produce the required retinoids il), in particular, retinal 2, which is essential for vision and is subsequently oxidized to retinoic acid 3 and reduced to retinol 4. An alternative excentric cleavage of 1 has been reported involving scission of the double bond at C7-C8 producing P-8 -apocarotenal 5 (2a,2b) which is subsequently oxidized to 2 (Fig. 1) (2c). The significance of carotene metabolites such as 2, 3 and 4 to embryonic development and other vital processes such as skin and membrane protection is a major concern of medicinal chemistry. 

A (carotene) Retinoic acid and retinol act as growth regulators, especially in epithelium Retinal is important in rod and cone cells for vision... 

Vitamin A (retinol) Animal tissue, liver, green plants Component of the pigment involved in vision... 

For vision to continue, c/s-retinal must be regenerated. The /rans-retinal is reduced to /rans-retinol (i.e. the aldehyde is converted to alcohol) and is isomerised to c/s-retinal this is oxidised to c/s-retinol (see Figure 15.9(b)). Two different cells are involved the oxidation of retinal to retinol occurs in the photoreceptor cell. The retinol is then released and is taken up by the adjacent epithelial cell where it is isomerised to c/s-retinol and then reduced to... 

Retinol can be oxidized to retinal (6.2) and further to retinoic acid (6.3). Cis-trans isomerization can also occur, e.g. the conversion of all trans-retinal to 11-cis-retinal (6.4), which is important for vision. 

The retinoids, a family of molecules that are related to retinol (vitamin A), are essential for vision, reproduction, growth, and maintenance of epithelial tissues. Retinoic acid, derived from oxidation of dietary retinol, mediates most of the actions of the retinoids, except for vision, which depends on retinal, the aldehyde derivative of retinol. 

Vitamin A Retinol Retinal Retinoic acid p-Carotene Retinol Retinal Retinoic acid FAT-SOLUBLE Maintenance of reproduction Vision Promotion of growth Differentiation and maintenance of epithelial tissues Gene expression... 

Vitamin A (retinol, retinal, retinoic acid—the three active forms of vitamin A, and p-carotene) function in the maintenance of reproduction, vision, promotion of growth, differen tiation and maintenance of epithelial tissues, and gene expression. A deficiency of vitamin A results in impotence, night blindness, retardation of growth, and xerophthalmia. Large amounts of vitamin A are toxic and can result in an increased incidence of frac tures. 

Vitamin A Precursor to rhodopsin, a chemical used for vision assists in inhibiting bacterial and viral infections Night blindness (retinol)... 

Vitamin A is a necessary micronutrient in the diet for vision, growth, tissue differentiation, reproduction, and maintenance of the immune system. A deficiency of vitamin A affects reproduction in both male and female experimental animals. In the male, retinol is required for normal spermatogenesis in the female, the vitamin is necessary for both conception and normal development of the fetus. 

Vitamin Vitamin A [retinol] RDA/AI Men 900 pg/d Women 700 pg/d Physiological function Required for normal vision, gene expression, reproduction, embryonic development, and immune function Adverse Effects of Excessive Consumption Teratological effects liver toxicity... 

This Chapter will present the actual chromophores of vision, labeled the Rhodonines and derivable from a number of feedstocks, including the retinol family, consist of relatively small molecules with a molecular weight of either 285 (R5 R9) or 299 (R7 R11). They are retinoids of the resonant conjugate type. They are also carboxylic-ion systems and exhibit a negative charge in their fundamental form. The molecules are relatively easily generated in the laboratory in pure form. However, they exhibit a number of unique properties that have made their isolation difficult. They only exhibit the properties of a visual chromophore when in the liquid crystalline state. Their absorption characteristic is a transient one unless a means of de-exciting the molecules of the liquid crystal is present. Finally, they are extremely sensitive to destruction by oxidants and alkali metal ions. 

Since the time of Wald s demonstration that rhodopsin, the conceptual chromophore of vision relied upon retinol as a chromogen and Hubbard s contemporary proposal that photodetection involved an isomerism of the chromophore, the conventional wisdom has adopted that position. To support these proposals, Collins proposed that a Shiff-base was... 

Based on some early work in the 1930 s, the assumption has been that the chromophores of vision are based on retinol or retinal coupled to a protein, opsin, in such a way as to form a chromophore. The variation in the location and possibly the style of couphng has been assumed to account for the actual spectral absorption of the material. After massive efforts, this premise has still not been demonstrated. However, it has caused a great deal of concentration on retinol and retinal as the fundamental structure of the chromophores. To this day, no laboratory experiments have shown either of these two retinoids exhibit a spectral absorption characteristic matching those of vision, human or otherwise. The retinols are neither chromophores nor analogs of the chromophores of vision. 

This work takes a completely different pathbased on the application of scientific tools unknown before the 1960 s, and still essentially unknown in the biological literature. It also incorporates a set of retinoid molecules into the theory of vision that can be shown to have the required chromophoric properties that Vitamin A aldehyde clearly does not possess. Neither retinol modified by a Schiff base nor further protonation of that Schiff base offers the required absorption spectrum18. 

The triplet state of the unpaired electrons of oxygen play a key role in both the photon excitation and the potential relaxation mode of the excited chromophores of vision. The paramagnetic properties of oxygen provide a definitive method of determining whether oxygen is present in the chromophores of vision, a condition that would eliminate the Shiff-base theory of retinol reaction with opsin to form rhodopsin. The evaluation of the electron paramagnetic resonance of the chromophores of vision is discussed in Chapter 7. 

The remainder of this section will assume that the chromophores of vision are the resonant conjugate retinoids derivable from Retinol and they have no chemical relationship to any protein, such as Opsin, except possibly through hydrogen bonding as a matter of convenience. Any more complex relationship would probably involve an undesired shift in spectra. 

Retinol, (a.k.a. Vitamin A) is a well-known chemical with many different properties and uses. These properties fall in many categories, some quite far removed from the obvious pharmacological ones and some which are virtually unknown in the literature. It is important to examine a number of these properties before exploring how retinol and its derivatives participate in the vision process. Because of its peripheral nature, relative to vision, this discussion will be found in Chapter 6. 

While the chromophores of vision are retinoids, derive from retinol in the biological environment, they are characterized by many features not shared with the retinenes. 

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