Retinol conversion

Because of the presence of an extended polyene chain, the chemical and physical properties of the retinoids and carotenoids are dominated by this feature. Vitamin A and related substances are yellow compounds which are unstable in the presence of oxygen and light. This decay can be accelerated by heat and trace metals. Retinol is stable to base but is subject to acid-cataly2ed dehydration in the presence of dilute acids to yield anhydrovitamin A [1224-18-8] (16). Retro-vitamin A [16729-22-9] (17) is obtained by treatment of retinol in the presence of concentrated hydrobromic acid. In the case of retinoic acid and retinal, reisomerization is possible after conversion to appropriate derivatives such as the acid chloride or the hydroquinone adduct. Table 1 Hsts the physical properties of -carotene [7235-40-7] and vitamin A. 

Scott KJ and Rodriguez-Amaya D. 2000. Pro-vitamin A carotenoids conversion factors retinol equivalents-fact or fiction Food Chem 69 125-127. 

Tanumihardjo SA. 2002. Factors influencing the conversion of carotenoids to retinol bioavailability to bioconversion to bioefficacy. Int J Vitam Nutr Res 72 40-5. 

Retinal, an aldehyde, is reactive with amino groups of proteins. Retinol, an alcohol, is not. The conversion of retinol to retinal is, therefore, critical. 

Figure 15.11 The biochemical reactions that result in the conversion of trans-retinal to ds-retinal, to continue the detection of light To continue the process, trans-retinal must be converted back to c/s-retinal. This is achieved in three reactions a dehydrogenase converts trans-retinal to trans-retinol an isomerase converts the trans-retinol to c/s-retinol and another dehydrogenase converts c/s-retinol to c/s-retinal. To ensure the process proceeds in a clockwise direction (i.e. the process does not reverse) the two dehydrogenases are separated. The trans-retinal dehydrogenase is present in the photoreceptor cell where it catalyses the conversion of trans-retinal to trans-retinol which is released into the interstitial space, from where it is taken up by an epithelial cell. Here it is isomerised to c/s-retinol and the same dehydrogenase catalyses its conversion back to c/s-retinal. This is released by the epithelial cell into the interstitial space from where it is taken up by the photoreceptor cell. This c/s-retinal then associates with the protein opsin to produce the light-sensitive rhodopsin to initiate another cycle. The division of labour between the two cells may be necessary to provide different NADH/NAD concentration ratios in the two cells. A high ratio is necessary in the photoreceptor cell to favour reduction of retinal and a low ration in the epithelial cell for the oxidation reaction (Appendix 9.7).

Metabohc derivatives of the fat-soluble vitamin retinol, which was first described in 1913. These metabolites play a central role in the visual process where the primary photoevent is attended by conversion of ll-cA-retinal to all-rrans-retinal. The oxidized metabolite retinoic acid is an agonist in cell growth and proliferation. 

In the body retinol can also be made from the vitamin precursor carotene. Vegetables like carrots, broccoli, spinach and sweet potatoes are rich sources of carotene. Conversion to retinol can take place in the intestine after which retinyl esters are formed by esterifying retinol to long chain fats. These are then absorbed into chylomicrons. Some of the absorbed vitamin A is transported by chylomicrons to extra-hepatic tissues but most goes to the liver where the vitamin is stored as retinyl palmitate in stellate cells. Vitamin A is released from the liver coupled to the retinol-binding protein in plasma. 

Since alcohol dehydrogenase is required for the conversion of retinol to retinal, excessive and prolonged ethanol ingestion can impair the physiological function of vitamin A. The decreased conversion of retinol to retinal results from competitive use of the enzyme by ethanol. Night blindness may result, since the visual cycle is a retinol-dependent physiological process. 

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 stereo-chemistry of retinol is well known in the pharmacological literature. However, conversion of retinol into Rhodonine introduces a heavy atom at an asymmetrical location in the structure and the resulting molecules are distinctly non-planar. 

A method has been presented for the determination of retinal (pug levels) by conversion into the intensely coloured and fluorescent derivative of 2-diphenylacetylindane-l,3-dione-l-hydrazone.82 The voltammetric oxidation of retinol at a carbon paste electrode has also been used to assay retinol.83... 

The biological activities of vitamin A and previtamin A are not equivalent on a per-weight basis. In humans, 6.0 mg of p-carotene is equivalent to 1.0 mg of retinol. Twelve milligrams of the other carotenoids is equivalent to 1-0 mg of retinol. The relatively low biological activity of the carotenoids is due to the inefficiency in their conversion to retinol and their ioivet availability u/beti present in foods. When -carotene is provided in pure form (dissolved in some oil and swallowed) its value is still less than that of vitamin A, Here, 2.0 mg of p-carotenc is equivalent to l.O mg of retinol. 

CRBP is thought to assure that retinol is metaboliby specific enzymes, white preventing metabolism by other en ymes. Por example, by binding retinol, CRBP prevents excessive rates of conversion of retinol to retinoic add (Napoli, 1996). 

In contrast to retinoids, carotenoids were considered non-toxic, even when taken chronically in large amounts, until recently, when it was found that ethanol interacts with carotenoids, interfering with their conversion to retinol. In baboons, the consumption of ethanol together with beta-carotene resulted in more striking hepatic injury than consumption of either compound alone (98). This interaction occurred at a total dose of 7.2-10.8 mg of beta-carotene per Joule of diet. This dose is common in people who take supplements and is the same order of magnitude used in the Beta-Carotene and Retinol Efficacy Trial (CARET) (30 mg/day) (99) and in another study (20 mg/day for 12 weeks) (100). The amount of alcohol given to the baboons was equivalent to that taken by an average alcohohc. The well-known toxicity... 

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